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Biomedical subjects

A Peretz

Publications and source records attributed to A Peretz.

At least 37 records · Page 2Linked to original sources

Efficiency of quantitative ultrasound measurements as compared with dual-energy X-ray absorptiometry in the assessment of corticosteroid-induced bone impairment.

Bone loss due to corticosteroid treatment differs from that of postmenopausal osteoporosis with regard to bone structure. Corticosteroids affect both horizontal and vertical trabeculae while horizontal trabeculae are damaged in postmenopausal osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the gold standard to evaluate bone loss. The place of quantitative ultrasound (QUS), a technique that could theoretically provide information on bone structure, is not well established in corticosteroid-induced bone impairment. The aim of the study was to determine the usefulness of QUS in the assessment of corticosteroid-induced bone impairment. We hypothesized that the relationship between QUS and DXA could be influenced by changes in bone structure and thus differ with regard to corticosteroid treatment. Seventy-seven women with inflammatory diseases chronically treated with corticosteroids (dose: 7.5-15 mg/day), 29 without corticosteroids and 100 controls were investigated. Bone mineral density at the lumbar spine (BMDL) was measured by DXA and QUS parameters were measured at the calcaneus. Both the QUS parameters (SOS, BUA, Stiffness) and BMDL were significantly lower (by 1.3% for SOS, 5.8% for BUA, 12.7% for Stiffness and 11% for BMDL) in patients treated with corticosteroids compared with patients not taking corticosteroids and with controls (p < 0.001, ANCOVA, with age and height as covariates). Multiple linear regressions of Stiffness, SOS and BUA as dependent variables on age, BMDL, corticosteroid treatment and a computed new variable designed to test the interaction between BMDL and the treatment group showed that Stiffness, SOS and BUA were dependent on age and BMDL (p < 0.001); BUA and Stiffness were dependent on treatment group. Taking into account the age of the patients, a significant difference was observed in the relation between BUA and BMDL according to treatment with corticosteroids. A similar difference was found in the subgroup of patients without fractures. SOS and BUA were strongly correlated but their relation did not differ according to treatment. Thus, QUS is useful in the assessment of corticosteroid-associated bone loss. Furthermore, the observation of a significant difference in the relationship between BUA and BMDL with regard to corticosteroid treatment might support the hypothesis that QUS, especially BUA, could give additional information about bone structure.

Absorptiometry, Photon↗

Evaluation of quantitative ultrasound and dual X-Ray absorptiometry measurements in women with and without fractures.

Dual X-ray absorptiometry (DXA) is considered a gold standard for bone measurements in the assessment of osteoporosis. Other techniques such as quantitative ultrasound (QUS) are promising to detect patients with osteoporosis-related fractures and to predict fracture risk. In this cross-sectional retrospective study, we analyzed the behavior of QUS and DXA measurements alone and in combination with regard to the presence of fractures in 320 women, 147 with nontraumatic fractures. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and a third parameter derived from SOS and BUA called stiffness were measured at the calcaneus using an Achilles device (Lunar, Madison, WI). Lumbar (BMDL) and hip (BMDH( bone mineral density were measured by DXA (Hologic QDR 1000, Waltham, MA). Mean SOS, BUA, stiffness, and BMDL and BMDH were significantly lower in women with fractures compared with women without fractures. Logistic regression adjusted for age identified stiffness as the parameter most strongly associated with the presence of fracture: its sensitivity was 54% and specificity 70%. Hip BMD was second, with a sensitivity of 54% and a specificity of 69%. Combining QUS and DXA measurements did not improve the specificity nor the sensitivity. There was no difference in the odds ratios with regard to the technique that was chosen for bone assessment. In conclusion, these results suggest that low QUS measurements are associated with the presence of fractures in a way similar to DXA. In our study, the combination of QUS and DXA did not improve the discrimination of women with fractures.

Absorptiometry, Photon↗

Heteromultimeric delayed-rectifier K+ channels in schwann cells: developmental expression and role in cell proliferation.

Schwann cells (SCs) are responsible for myelination of nerve fibers in the peripheral nervous system. Voltage-dependent K+ currents, including inactivating A-type (KA), delayed-rectifier (KD), and inward-rectifier (KIR) K+ channels, constitute the main conductances found in SCs. Physiological studies have shown that KD channels may play an important role in SC proliferation and that they are downregulated in the soma as proliferation ceases and myelination proceeds. Recent studies have begun to address the molecular identity of K+ channels in SCs. Here, we show that a large repertoire of K+ channel alpha subunits of the Shaker (Kv1.1, Kv1.2, Kv1.4, and Kv1.5), Shab (Kv2.1), and Shaw (Kv3.1b and Kv3.2) families is expressed in mouse SCs and sciatic nerve. We characterized heteromultimeric channel complexes that consist of either Kv1.5 and Kv1.2 or Kv1.5 and Kv1.4. In postnatal day 4 (P4) sciatic nerve, most of the Kv1.2 channel subunits are involved in heteromultimeric association with Kv1.5. Despite the presence of Kv1. 1 and Kv1.2 alpha subunits, the K+ currents were unaffected by dendrotoxin I (DTX), suggesting that DTX-sensitive channel complexes do not account substantially for SC KD currents. SC proliferation was found to be potently blocked by quinidine or 4-aminopyridine but not by DTX. Consistent with previous physiological studies, our data show that there is a marked downregulation of all KD channel alpha subunits from P1-P4 to P40 in the sciatic nerve. Our results suggest that KD currents are accounted for by a complex combinatorial activity of distinct K+ channel complexes and confirm that KD channels are involved in SC proliferation.

Aging↗

A Ca2+/calmodulin-dependent protein kinase modulates Drosophila photoreceptor K+ currents: a role in shaping the photoreceptor potential.

Light activation of Drosophila photoreceptors leads to the generation of a depolarizing receptor potential via opening of transient receptor potential and transient receptor potential-like cationic channels. Counteracting the light-activated depolarizing current are two voltage-gated K+ conductances, IA and IK, that are expressed in these sensory neurons. Here we show that Drosophila photoreceptors IA and IK are regulated by calcium-calmodulin (Ca2+/calmodulin) via a Ca2+/calmodulin-dependent protein kinase (CaM kinase), with IK being far more sensitive than IA. Inhibition of Ca2+/calmodulin by N-(6 aminohexyl)-5-chloro-1-naphthalenesulfonamide or trifluoperazine markedly reduced the K+ current amplitudes. Likewise, inhibition of CaM kinases by KN-93 potently depressed IK and accelerated its C-type inactivation kinetics. The effect of KN-93 was specific because its structurally related but functionally inactive analog KN-92 was totally ineffective. In Drosophila photoreceptor mutant ShKS133, which allows isolation of IK, we demonstrate by current-clamp recording that inhibition of IK by quinidine or tetraethylammonium increased the amplitude of the photoreceptor potential, depressed light adaptation, and slowed down the termination of the light response. Similar results were obtained when CaM kinases were blocked by KN-93. These findings place photoreceptor K+ channels as an additional target for Ca2+/calmodulin and suggest that IK is well suited to act in concert with other components of the signaling machinery to sharpen light response termination and fine tune photoreceptor sensitivity during light adaptation.

Adaptation, Ocular↗

Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells.

In the nervous system, Src family tyrosine kinases are thought to be involved in cell growth, migration, differentiation, apoptosis, as well as in myelination and synaptic plasticity. Emerging evidence indicates that K+ channels are crucial targets of Src tyrosine kinases. However, most of the data accumulated so far refer to heterologous expression, and native K+-channel substrates of Src or Fyn in neurons and glia remain to be elucidated. The present study shows that a Src family tyrosine kinase constitutively activates delayed-rectifier K+ channels (IK) in mouse Schwann cells (SCs). IK currents are markedly downregulated upon exposure of cells to the tyrosine kinase inhibitors herbimycin A and genistein, while a potent upregulation of IK is observed when recombinant Fyn kinase is introduced through the patch pipette. The Kv1.5 and Kv2.1 K+-channel alpha subunits are constitutively tyrosine phosphorylated and physically associate with Fyn both in cultured SCs and in the sciatic nerve in vivo. Kv2.1- channel subunits are found to interact with the Fyn SH2 domain. Inhibition of Schwann cell proliferation by herbimycin A and by K+-channel blockers suggests that the functional linkage between Src tyrosine kinases and IK channels could be important for Schwann cell proliferation and the onset of myelination.

Animals↗

Comparative study of the intestinal absorption of three salts of calcium in young and elderly women.

A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D supplement is presently considered to be the adequate and least expensive therapy for senile osteoporosis. There exists only scarce data about calcium absorption with available calcium salts in elderly patients. We have compared the digestive absorption of calcium (Ca) citrate in soluble and solid form and calcium gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral calcium loading test. The subjects were divided into two groups. In the first group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young (n = 7) and elderly women (n = 10). In the second group, the absorption of soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) in young (n = 8) and elderly (n = 10) women. In the preload phase, basal calciuria was increased in elderly women (p < 0.01) although basal calcemia was similar in young and elderly women. After oral administration of the calcium salts, an increase in plasma Ca was observed in both groups which was greater for soluble Ca citrate and Ca gluconolactate than for solid Ca citrate. In young women, the increase in plasma calcium was significantly higher with soluble Ca citrate compared to Ca gluconolactate (p < 0.05). In elderly women, the postload calciuria was significantly higher for soluble Ca citrate (p < 0.05) and Ca gluconolactate (p < 0.05) compared to solid Ca citrate. A similar pattern was observed in young women, although it was not significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca gluconolactate-carbonate induces significant biochemical changes suggesting a better digestive absorption compared to Ca citrate in solid form, both in young and elderly women. We did not observe different response, between young and old patients.

Adult↗

[Pharmacoeconomics of menopause treatments: epidemiological data and hormonal and non-hormonal prescription attitude of Belgian gynecologists].

In an economic analysis one has not only to consider costs induced by hormonal substitution therapy (HRT) but also its impact health. Different therapy costs will be considered and related to potential benefits on health. HRT decreases the incidence of symptoms of the menopause, the risk of osteoporosis and perhaps the incidence of coronary hearth disease and the risk of Alzheimer disease but probably increases the incidence of breast cancer. For a majority of women, the favorable impact seems to dominate, increasing their life expectancy.

Aged↗

[Evaluation of the cost of non-hormonal treatment of osteoporosis].

Osteoporosis is a disease affecting a large population of postmenopausal women. The treatment is given for a period of 5, 10, 20 years.... The cost of the treatment plays an important role in the field of health economy. A commercial form of calcium and vitamin D for 10 years represent for the patient a cost of 50,000 BF. The other treatments, alternative to hormonal substitution, have variable prices, for biphosphonates, 50,000 to 500,000 for the insurance and from 1,000 to 5,000 BF for the patient having a regular insurance. A comprehensive choice in long term treatment should take into account efficacy and cost of the treatment.

Calcitonin↗

[New NSAIDS: COX-1, COX-2, what about them?].

Non steroidal antiinflammatory (NSAID) drugs are the most widely prescribed drugs against pain and inflammation. Problems of tolerance, particularly gastrointestinal toxicity, limit their use. The central mechanism of NSAID action is the reduction of prostaglandin production from arachidonic acid through cyclooxygenase inhibition. Although such a mechanism was already described 25 years ago, the recent discovery of two isoforms of cyclooxygenase, the cyclooxygenase 1 (COX-1) constitutively expressed in most tissues and the cyclooxygenase 2 (COX-2), inducible, has prompted research in developing new NSAID that would be safer whilst maintaining their efficacy. Nevertheless, their long term efficacy and safety need to be demonstrated in clinical practice. There are still unsolved questions, especially about the physiological role of COX-2.

Animals↗

Cyclical pamidronate infusions in postmenopausal osteoporosis.

OBJECTIVES: Until recently, two bisphosphonates, pamidronate (APD) and etidronate were available for clinical purposes. Contrary to etidronate, pamidronate was not extensively studied in osteoporosis. Therefore, we investigated the effect of cyclic intravenous APD treatment in postmenopausal osteoporosis. METHODS: Parameters of bone remodelling and lumbar spine bone mineral density (BMDL) were assessed in 36 postmenopausal women with osteoporosis (BMDL t-score < -2.5). They received five courses of APD. Intervals between courses were defined according to the fasting urinary calcium excretion (UCa/Cr, mg/mg creatinine) which was measured before each APD course and every 2 weeks after the first treatment. The patients were retreated when UCa/Cr had reached baseline levels. Serum biochemical parameters and urinary hydroxyproline (UOHPro/Cr, mg/mg) were measured before each APD. RESULTS: UCa/Cr decreased during 21-28 days after each course but UCa/Cr measured before APD infusion remained unchanged. UOHPro/Cr significantly fell after the third APD (P = 0.02). Serum calcium was however not modified. Parameters of bone remodelling decreased with time: bone-GLA protein (BGP) started to fall after the first APD (P = 0.0001) and continued to decrease until the fourth APD course, alkaline phosphatase (ALP) significantly decreased after the first APD (P = 0.005); intact PTH significantly increased at the fifth APD (P = 0.02). BMDL significantly increased after 1 year treatment: +2.9% of baseline value. CONCLUSIONS: Cyclical pamidronate treatment of postmenopausal osteoprosis appeared to be effective in reducing bone turnover assessed by BGP, ALP and OHPro/Cr. This effect is followed by an increase in vertebral BMD.

Adult↗

Quantitative ultrasound bone measurements: normal values and comparison with bone mineral density by dual X-ray absorptiometry.

Normative data for qualitative ultrasound (QUS) measurements: speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were established in 118 healthy women aged 20-86 years and in 42 healthy men aged 22-76 years. The relations between age, weight, height, and QUS were studied. QUS measurements were negatively correlated with age in both sexes. In women, age was accepted as first factor (R2 = 0.39 for SOS, 0.35 for BUA, and 0.45 for stiffness, P < 0.001); weight was accepted as second factor for BUA (R2 = 0.44, P < 0.001). In men, age was the only significant parameter (R2 = 0.41 for SOS, 0.39 for BUA, 0.43 for stiffness, P < 0.001). QUS measurements of the right and left feet were highly correlated unless unilateral foot pathology such as algodystrophy was present. Significant correlations were found between QUS of the calcaneus and dual X-ray absorptiometry (DXA) of the lumbar spine (R = 0.67, P < 0.01 for SOS; R = 0.57, P < 0.02 for BUA; R = 0.65, P < 0.01 for stiffness).

Absorptiometry, Photon↗

Precision and accuracy of in vivo bone mineral measurement in rats using dual-energy X-ray absorptiometry.

The aim of this study was to evaluate the precision and accuracy of dual-energy X-ray absorptiometry (DXA) for measuring bone mineral content at different sites of the skeleton in rats. In vitro the reproducibility error was very small (< 1%), but in vivo the intra-observer variability ranged from 0.9% to 6.0%. Several factors have been shown to affect in vivo reproducibility: the reproducibility was better when the results were expressed as bone mineral density (BMD) rather than bone mineral content (BMC), intra-observer variability was better than the inter-observer variability, and a higher error was observed for the tibia compared with that for vertebrae and femur. The accuracy of measurement at the femur and tibia was assessed by comparing the values with ash weight and with biochemically determined calcium content. The correlation coefficients (R) between the in vitro BMC and the dry weight or the calcium content were higher than 0.99 for both the femur and the tibia. SEE ranged between 0.0 g (ash weight) and 2.0 mg (Ca content). Using in vitro BMC, ash weight could be estimated with an accuracy error close to 0 and calcium content with an error ranging between 0.82% and 6.80%. The R values obtained between the in vivo and in vitro BMC were 0.98 and 0.97 respectively for femur and tibia, with SEE of 0.04 and 0.02 g respectively. In conclusion, the in vivo precision of the technique was found to be too low. To be of practical use it is important in the design of experimentation to try to reduce the measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Clinical significance of heterogeneity of vertebral mineral density.

Important variations in Z-score per vertebra, which is a common expression of bone mineral density (BMD), are sometimes observed. The present study evaluates the clinical significance of this heterogeneity. Normal and osteoporotic subjects were defined by using strict criteria. For every scan, the minimal Z-score (the vertebra with the lowest Z-score) and the delta Z (highest Z-score--lowest Z-score) was calculated. Of the investigated subjects, 30% presented a delta Z > or = 1. No significant correlation could be found between delta Z and age, BMD, height and weight. There was no difference in delta Z between scans of good, average or poor quality. Osteoporotic subjects had significantly lowered BMD values, whether evaluated through Z-scores for the L2-L4 site (P < 0.001; t = 3.71) or by minimal Z-score (P < 0.001; t = 3.97). Reproducibility calculated for the L2-L4 site on phantoms as well as on patients was excellent (C.V. < 1%). When reproducibility was calculated on each vertebra in vitro or in vivo, an increase in variability was observed. These data show that marked heterogeneity in BMD per vertebra is not infrequent. In some subjects low BMD may be measured at certain vertebrae but not at the total site. Our data suggest that in those cases the lowest BMD should be considered. In follow-up studies however, the BMD should be calculated on the L2-L4 segment, since a loss of precision is observed when only one vertebra is measured.

Absorptiometry, Photon↗

SPECT diagnosis of Creutzfeld-Jacob disease.

SPECT with 99mTc-HMPAO was performed on a 65-yr-old patient with Creutzfeld-Jacob disease. Cerebral blood flow was heterogeneously decreased throughout the brain, differing from the pattern observed in other common types of dementia. These results suggest that HMPAO-SPECT may provide useful information in the differential diagnosis of dementia, specifically when Creutzfeld-Jacob disease is suspected.

Aged↗

TRP, a protein essential for inositide-mediated Ca2+ influx is localized adjacent to the calcium stores in Drosophila photoreceptors.

The Drosophila transient receptor potential (trp) gene product (TRP) shows some structural similarity to vertebrate voltage-gated Ca2+ channels. It appears to function as a novel Ca2+ channel responsible for light stimulated, inositol trisphosphate (InsP3)-mediated Ca2+ entry in the fly retina. The subcellular localization of TRP protein was determined in this study using immunohistochemical staining with anti-TRP antibody (MAb83F6). TRP was localized to the base of the microvilli in a region adjacent to the presumed InsP3-sensitive Ca2+ stores. This specific localization was supported by measuring the magnitude of a TRP-dependent inward current that results from spontaneous activation of the light-sensitive channels during whole-cell recordings (the rundown current, RDC). We found that reduction of the microvilli area through genetic dissection with the opsin null mutant, ninaEora, was correlated with a pronounced enhancement of the TRP-dependent inward current relative to wild type, suggesting that the TRP-dependent current was not produced along the length of the microvilli. We suggest that the functional localization of the TRP protein is on the plasma membrane loop found along the base of the rhabdomeric microvillus. Thus, the TRP channel may function in concert with the InsP3-sensitive Ca2+ stores.

Animals↗