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Biomedical subjects

L Roy

Publications and source records attributed to L Roy.

At least 37 records · Page 2Linked to original sources
PubMed2000

The Script Concordance test: a tool to assess the reflective clinician.

BACKGROUND: The Script Concordance (SC) test is a new assessment tool. It is designed to probe whether knowledge of examinees is efficiently organized for clinical actions. That kind of organization of knowledge is named a script. The SC test places examinees in written, but authentic, clinical situations in which they must interpret data to make decisions. PURPOSE: The SC test is designed to measure the degree of concordance that exists between examinees' scripts and scripts of a panel of experts. The objective of this article is to provide interested educators with the practical "how to" information needed to build and use an SC test. METHODS: The theoretical background of the SC test is described. The principles of construction of an SC test are presented, including the writing of clinical cases, the choice of item format, the validation of the test, and the elaboration of the scoring system. RESULTS: A series of studies have shown that the SC test has interesting psychometric properties, in terms of reliability, face validity, and construct validity. Results from these studies are succinctly presented and commented. CONCLUSION: The SC test is a simple and direct approach to testing organization and use of knowledge. It has the strong advantage for a testing method of being relatively easy to construct and use and to be machine-scorable. It can be either paper- or computer-based and can be used in undergraduate, postgraduate, or continuing medical education.

Adult↗
PubMed2000

Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays.

BACKGROUND: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. METHODS: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL. min(-1). 1.73 m(-2), 12 with a GFR between 30 and 60 mL. min(-1). 1.73 m(-2), and 8 with a GFR between 5 and 30 mL. min(-1). 1.73 m(-2). We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups. RESULTS: Only patients with a GFR <30 mL. min(-1). 1.73 m(-2) and hemodialyzed patients had decreased Ca(2+) and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca(2+) (r = -0.66; P <0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvitamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL. min(-1). 1.73 m(-2), and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. CONCLUSIONS: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL. min(-1). 1.73 m(-2). Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.

Adult↗
PubMed1999

Roles for alpha(2)p24 and COPI in endoplasmic reticulum cargo exit site formation.

A two-step reconstitution system for the generation of ER cargo exit sites from starting ER-derived low density microsomes (LDMs; 1.17 g/cc) is described. The first step is mediated by the hydrolysis of Mg(2+)ATP and Mg(2+)GTP, leading to the formation of a transitional ER (tER) with the soluble cargo albumin, transferrin, and the ER-to-Golgi recycling membrane proteins alpha(2)p24 and p58 (ERGIC-53, ER-Golgi intermediate compartment protein) enriched therein. Upon further incubation (step two) with cytosol and mixed nucleotides, interconnecting smooth ER tubules within tER transforms into vesicular tubular clusters (VTCs). The cytosolic domain of alpha(2)p24 and cytosolic COPI coatomer affect VTC formation. This is deduced from the effect of antibodies to the COOH-terminal tail of alpha(2)p24, but not of antibodies to the COOH-terminal tail of calnexin on this reconstitution, as well as the demonstrated recruitment of COPI coatomer to VTCs, its augmentation by GTPgammaS, inhibition by Brefeldin A (BFA), or depletion of beta-COP from cytosol. Therefore, the p24 family member, alpha(2)p24, and its cytosolic coat ligand, COPI coatomer, play a role in the de novo formation of VTCs and the generation of ER cargo exit sites.

Adenosine Triphosphate↗
PubMed1999

ST-segment depression and myocardial contractility during cesarean section under spinal anesthesia.

PURPOSE: To evaluate myocardial contractility during ST segment depression in healthy parturients during Cesarean section (CS). METHODS: Forty-seven consecutive term parturients undergoing elective CS under spinal anesthesia were studied. The ST segment was recorded continuously on leads II and V5 using a Holter monitor. Myocardial performance was evaluated by measuring cardiac index (CI), heart rate (HR), pre-ejection period (PEP), ventricular ejection time (VET), systolic time ratio (STR, PEP/VET), and ejection fraction (EF) with an impedance cardiograph. RESULTS: Fourteen patients (30%) developed ST segment depression within 15 min after delivery and the remaining 33 (70%) did not (controls). Seven patients developed a 1 mm change, five patients a 2 mm change and the remaining two a 3 mm change in the ST segment. Compared with pre-anesthesia values, the mean HR increased from 103 +/- 10 to 116 +/- 10 (ISD) bpm (P = 0.001), CI from 4.7 +/- 0.7 to 5.6 +/- 1.7 L.min-1 (P = 0.01), EF from 0.58 +/- 0.08 to 0.66 +/- 0.05 (P = 0.01) and STR decreased from 0.26 +/- 0.06 to 0.2 +/- 0.04 (P = 0.01) during ST segment depression. At this time, CI, HR and EF were greater and STR smaller than values obtained 15 min after delivery in the control subjects. CONCLUSION: ST-segment depression occurring during CS is associated with a hyperkinetic myocardial contractile state.

Adolescent↗
PubMed1999

Risk factors for recurrent urinary tract infection in preschool children.

OBJECTIVE: Children with urinary tract infections (UTI) are at risk of renal scarring which may lead to impaired renal function and hypertension. This study examines the risk factors that predispose to recurrent UTI in children and the role of recurrent UTI in renal scarring. METHODOLOGY: A group of 290 children under 5 years of age with a first symptomatic UTI were studied. Micturating cystourethrogram and dimercaptosuccinic acid (DMSA) renal scintigraphy were performed at entry, and DMSA was repeated 1 year later. Two hundred and sixty-one children (90%) were followed up at 1 year. RESULTS: There were 46 confirmed recurrent infections in 34 children, a recurrence rate of 12%. Multiple recurrence occurred in 14/34 (34%) children. Age of less than 6 months on entry independently predicted for recurrent UTI (odds ratio (OR): 2.9)). Compliance with prophylactic antibiotics fell throughout the year of follow up. Vesicoureteric reflux (VUR) was present in 14/34 (34%) of the group with recurrent UTI, 69/256 (27%) without recurrence. Urinary tract infection was significantly associated with bilateral and intrarenal reflux; grade 3-5 reflux independently predicted for recurrent UTI (OR: 3.5). Recurrent UTI was significantly associated with high grade DMSA defects on entry, renal parenchymal defects at 1 year follow up, and new defects at 1 year. CONCLUSION: The independent risk factors for recurrent UTI identified by this study were an age of less than 6 months at the index UTI and grade 3-5 VUR. These findings suggest more selective targeting may minimize problems associated with prophylaxis and improve outcomes for children with urine infection.

Anti-Infective Agents, Urinary↗
PubMed1999

Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly as a treatment for refractory ascites. The aim of the present study was to determine the prognostic value of different parameters in predicting a favorable evolution following TIPS in a cohort of 53 cirrhotic patients without organic renal disease and with refractory ascites. METHODS: Patients were classified as good responders if they survived more than 6 months, without severe chronic hepatic encephalopathy and with good control of ascites. The prognostic value for a good outcome was evaluated using age, creatinine clearance, plasma renin activity, plasma aldosterone, and Pugh score. RESULTS: Good control of ascites was obtained in 90%. The cumulative survival rate was 54% at 6 months, 48% at 1 yr, and 39% at 2 yr. The vast majority of patients died of complications of hepatic insufficiency. Severe chronic hepatic encephalopathy developed in 26%. Overall, a good clinical response was observed in 47%. Creatinine clearance was identified as the only pre-TIPS factor to be significantly and independently associated with a good clinical response to TIPS for refractory ascites. A good clinical response was observed in 57% of patients with a creatinine clearance >36 ml/min compared to 9% of those with a clearance <36 ml/min (p < 0.01). This cutoff point in creatinine clearance had a sensitivity of 96% and a specificity of 36%; positive predictive and negative predictive values were 57% and 90%, respectively. CONCLUSIONS: TIPS might be useful for the treatment of refractory ascites in cirrhotic patients without severe renal function impairment. However, the TIPS usefulness still has to be demonstrated compared to large volume paracentesis or Leveen shunt. In patients with poor renal function or with liver failure after TIPS, liver transplantation should be considered.

Adult↗
PubMed1998

Identification of quinine metabolites in urine after oral dosing in humans.

A gas chromatographic-mass spectrometric method was used to separate quinine and its metabolites present in urine after oral dosing of 300 mg quinine in humans. The technique allowed the separation of quinine and ten metabolites. Four of these metabolites were definitely identified as 3-hydroxyquinine, 2'-quinone, O-desmethylquinine and 10,11-dihydroxydihydroquinine, by comparing their methane chemical ionization mass spectra with those of authentic standards prepared by organic synthesis. Six other metabolites are described for the first time in human urine. From their electron impact and chemical ionization mass spectra, we propose these compounds to be 3-hydroxy-2'-quinone, O-desmethyl-2'-quinone, O-desmethyl-3-hydroxyquinine, O-desmethyl-3-hydroxy-2'-quinone, 10,11-dihydroxydihydro-2'-quinone and 10,11-dihydroxydihydro-O-desmethylquinine. These secondary metabolites probably arose from further biotransformation of the four primary metabolites.

Administration, Oral↗
PubMed1998

The unanticipated difficult airway with recommendations for management.

PURPOSE: To review the current literature and generate recommendations on the role of newer technology in the management of the unanticipated difficult airway. METHODS: A literature search using key words and filters of English language and English abstracted publications from 1990-96 contained in the Medline, Current Contents and Biological Abstracts databases was carried out. The literature was reviewed and condensed and a series of evidence-based recommendations were evolved. CONCLUSIONS: The unanticipated difficult airway occurs with a low but consistent incidence in anaesthesia practice. Difficult direct laryngoscopy occurs in 1.5-8.5% of general anaesthetics and difficult intubation occurs with a similar incidence. Failed intubation occurs in 0.13-0.3% general anaesthetics. Current techniques for predicting difficulty with laryngoscopy and intubation are sensitive, non-specific and have a low positive predictive value. Assessment techniques which utilize multiple characteristics to derive a risk factor tend to be more accurate predictors. Devices such as the laryngeal mask, lighted stylet and rigid fibreoptic laryngoscopes, in the setting of unanticipated difficult airway, are effective in establishing a patient airway, may reduce morbidity and are occasionally lifesaving. Evidence supports their use in this setting as either alternatives to facemask and bag ventilation, when it is inadequate to support oxygenation, or to the direct laryngoscope, when tracheal intubation has failed. Specifically, the laryngeal mask and Combitube have proved to be effective in establishing and maintaining a patent airway in "cannot ventilate" situations. The lighted stylet and Bullard (rigid) fibreoptic scope are effective in many instances where the direct laryngoscope has failed to facilitate tracheal intubation. The data also support integration of these devices into strategies to manage difficult airway as the new standard of care. Training programmes should ensure graduate physicians are trained in the use of these alternatives. Continuing medical education courses should allow physicians in practice the opportunity to train with these alternative devices.

Education, Medical, Continuing↗
PubMed1998

The set point of parathyroid hormone stimulation by calcium is normal in progressive renal failure.

An increased set point of PTH stimulation by ionized calcium (Ca++) has been observed in renal failure patients with severe secondary hyperparathyroidism. The extension of this concept to all renal failure patients has remained problematic, even if it could explain elevated PTH levels in the absence of other biochemical abnormalities. We were particularly interested in seeing whether the concept could fit patients with progressive renal failure (PRF). To achieve this, we studied 26 normals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in the basal state and during parathyroid function tests. The latter two groups were studied at the end of winter and end of summer, respectively. Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)2D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinine levels. HD had significantly lower levels of Ca++ and 1,25(OH)2D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 28.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I-PTH was increased 2-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.001 vs. others). But the set point of I-PTH stimulation by Ca++ was normal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not significant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. others). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between serum Ca++ concentration and the set point value when all three populations were analyzed together (r = 0.759, n = 47, P < 0.0001). These results indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the ambient Ca++ concentration of the patients, by mechanisms yet to be elucidated. This does not suggest participation of this factor to the genesis of the secondary hyperparathyroidism of PRF.

Adult↗
PubMed1998

A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples.

We have previously shown that the Nichols assay for intact parathyroid hormone (I-PTH) reacts with a non-(1-84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates in renal failure, accounting for 40-60% of the measured immunoreactivity. We wanted to see whether this was a common event with other commercial two-site I-PTH assays. We thus compared the ability of three commercial kits [Nichols (NL), Incstar (IT), and Diagnostic System Laboratories (DSL)] to measure I-PTH in 112 renal failure patients and to detect hPTH(1-84) and non-(1-84)PTH on HPLC profiles of serum pools from uremic patients with I-PTH concentrations of 10-100 pmol/L. The behavior of synthetic hPTH(7-84), a fragment possibly related to non-(1-84)PTH was also compared with hPTH(1-84) in the three assays. The I-PTH concentrations measured with the three assays in the 112 uremic samples were highly related (r2 > or = 0.89, P < 0.0001), and the values measured with NL were, on average, 23% higher than IT. Values measured with DSL were 23% and 56% higher than IT for values less than and more than 40 pmol/L, respectively. The three assays detected two HPLC peaks on four different profiles corresponding to hPTH(1-84) and non-(1-84)PTH. This last peak represented 36 +/- 8.4% of the immunoreactivity with NL, 24 +/- 5.5% with IT, and 25 +/- 2.8% with DSL (NL vs IT or DSL: P < 0.05). These differences were confirmed by a 50% lower immunoreactivity to hPTH(7-84) compared with hPTH(1-84) for IT and DSL but not for NL. These results suggest that most of the two-site I-PTH assays would cross-react with non-(1-84)PTH material, thus explaining about one-half of the 2-2.5 x higher I-PTH concentrations reported in uremic patients without bone involvement than in subjects without uremia.

Chromatography, High Pressure Liquid↗
PubMed1998

Glomerular filtration rate measurement in cirrhotic patients with renal failure.

Assessment of renal function, namely glomerular filtration rate (GFR), by the renal creatinine clearance, may be problematic and less accurate in cirrhotics; however, it is an essential element in the global evaluation of these patients. In order to better characterize misinterpretation of GFR by the renal creatinine clearance, we compared a group of cirrhotic patients with renal failure (n - 30) to a group of chronic renal failure patients (CRF) without liver disease (n - 5). Inulin and PAH clearances were measured during a 4-hour infusion of inulin and PAH; renal creatinine clearance was measured during a 24-hour urine collection and this, simultaneously with inulin and PAH clearance. We observed that in moderate to severe renal failure (renal inulin clearance 30 +/- 10 ml/min), GFR (i. e. renal inulin clearance) in cirrhotic patients was overestimated by the renal creatinine clearance, similarly to CRF patients (ratio 1.8 +/- 0.7 and 1.6 +/- 0.9 respectively); however cirrhotic patients have a lower serum creatinine (186 +/- 97 vs 133 +/- 62 micromol/l respectively). On the other hand, cirrhotic patients with mild renal dysfunction (renal inulin clearance 74 +/- 15 ml/min) had a renal creatinine clearance of 77 +/- 25 ml/min. Systemic inulin clearance overestimated renal inulin clearance, proportionally to the severity of renal dysfunction. We conclude that it is only the degree of renal failure, irrespective of etiology, that explains the overestimation of the glomerular filtration rate by the renal creatinine clearance in cirrhotic patients; hence, there is no specific alteration in the renal excretion of creatinine in cirrhotic patients.

Creatinine↗
PubMed1997

Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary angioplasty: evidence for oxidant stress during coronary reperfusion in humans.

BACKGROUND: The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical-catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: We developed specific, mass spectrometry assays for two structurally distinct F2 isoprostanes, 8-epi-PGF2alpha and IPF2alpha-I. Urine samples for isoprostane determination were collected in patients undergoing coronary arteriography (n=11), elective PTCA (n=15), and angiography after thrombolysis for acute myocardial infarction (MI) (n=10). Urinary levels (pmol/mmol creatinine) of both isoprostanes were markedly increased from baseline in the first 6 hours after PTCA for acute MI (105+/-17.8 versus 230+/-66 for 8-epi-PGF2alpha [P=.009] and 466+/-91 versus 833+/-153 for IPF2alpha-I [P=.001]) and returned toward preprocedural values by 24 hours (122+/-18 for 8-epi-PGF2alpha and 457+/-102 for IPF2alpha-I). There was a slight increase in urinary 8-epi-PGF2alpha levels (64.7+/-9.5 versus 84.9+/-10.6; P=.02) after diagnostic coronary arteriography and elective PTCA (88.7+/-7.5 versus 114.3+/-16.1; P=.01). A striking correlation was observed (r=.68, P<.0001; n=33) between urinary 8-epi-PGF2alpha and IPF2alpha-I levels in patients receiving thrombolytic agents for acute MI. CONCLUSIONS: Urinary F2 isoprostane levels are elevated in patients after treatments resulting in reperfusion for acute MI. These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isoprostanes may offer a noninvasive approach to the assessment of oxidant stress and the efficacy of antioxidant therapies in these syndromes.

Aged↗
PubMed1997

New sheath for vascular access and subcutaneous drug administration: multicenter clinical trial for pain prevention after cardiac catheterization.

A new vascular sheath design (anesthesia infusion sleeve, or AIS) was developed to enable administration of local anesthetics or other medications into the subcutaneous tissue around an arterial or venous insertion site without any additional needle sticks or manipulation. Design, animal testing, and an initial small single-site clinical study have previously been published. The current study was multicenter and randomized 80 patients to use of a standard sheath for vascular access or the AIS. Pain associated with sheath placement, postprocedure pain, and pain associated with sheath removal before and during manual compression was recorded. Baseline pain was identical in both the standard and AIS groups. Pain during infiltration and with initial femoral artery compression was significantly lower in the AIS group. A quality of life questionnaire indicated that the AIS sheath was associated with less discomfort and was preferred over a standard sheath in patients who had had a previous procedure performed. The AIS represents a simple addition to standard sheath design, offering superior pain control during removal compared to the standard technique, without the need for systemic analgesics or additional needle punctures.

Adult↗
PubMed1997

Expression, purification from inclusion bodies, and crystal characterization of a transition state analog complex of arginine kinase: a model for studying phosphagen kinases.

Phosphagen kinases catalyze the reversible transfer of a phosphoryl group between guanidino phosphate compounds and ADP, thereby regenerating ATP during bursts of cellular activity. Large quantities of highly pure arginine kinase (EC 2.7.3.3), the phosphagen kinase present in arthropods, have been isolated from E. coli, into which the cDNA for the horseshoe crab enzyme had been cloned. Purification involves size exclusion and anion exchange chromatographies applied in the denatured and refolded states. The recombinant enzyme has been crystallized as a transition state analog complex. Near complete native diffraction data have been collected to 1.86 A resolution. Substitution of a recombinant source for a natural one, improvement in the purification, and data collection at cryo temperatures have all yielded significant improvements in diffraction.

Animals↗
PubMed1997

Treatment of refractory ascites using transjugular intrahepatic portosystemic shunt (TIPS): a caution.

Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic patients, who then require repeated large-volume paracentesis. In this prospective study we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4 +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients following TIPS. Ascites recurrence associated with shunt stenosis was observed during follow-up in eight patients; revision could be undertaken in five of them and resulted in good control of ascites. In responders, a marked decrease in plasma aldosterone and renin activity, a reduction in serum creatinine, and a rise in urinary sodium excretion were observed. Creatinine and inulin clearances improved significantly; PAH clearance remained unchanged. However, new-onset or worsening hepatic encephalopathy was seen in 14 patients. Severe disabling chronic encephalopathy occurred in five patients; it could be reversed successfully by balloon occlusion of the shunt in three. The cumulative survival rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control refractory ascites in a majority of patients but is associated with a high rate of chronic disabling HE. In addition, the survival rate is poor. Randomized trials are needed to evaluate the exact role of TIPS in the management of refractory ascites. It is unlikely to improve survival but can ameliorate quality of life in nontransplant candidates and be useful as a bridge to transplantation, in particular, to improve denutrition associated with longstanding tense ascites.

Aged↗
PubMed1997

Is FISH painting an appropriate biological marker for dose estimates of suspected accidental radiation overexposure? A review of cases investigated in France from 1995 to 1996.

From 1995 to 1996 about 15 people suspected of being overexposed to ionizing radiation were referred to the Institute for Nuclear Safety and Protection in Fontenay-aux-Roses, France, for investigation by chromosome aberration analysis. Biological estimates of accidental overexposure were first obtained by scoring radio-induced unstable structural chromosome aberrations (dicentrics, centric rings, and fragments) in peripheral blood lymphocytes. For dose estimates, the yield of these chromosomal aberrations observed in 500 metaphases was compared with the laboratory dose-response relationship established from human blood irradiated in vitro (gamma-rays, 60Co, 0.5 Gy/min). To extend the possibilities of detecting DNA damage from earlier exposures by visualizing stable chromosome aberrations, chromosome painting by fluorescence in situ hybridization (FISH painting) was developed using a cocktail of three composite whole human chromosome-specific DNA probes (numbers 2, 4, and 12). A laboratory calibration curve for scoring terminal and/or reciprocal translocations was established for the same radiation quality and dose rate as those used for conventional cytogenetics (gamma-rays, 60Co, 0.5 Gy/min). For dosimetry purposes, it was also important to verify whether FISH painting could be applied to each human blood sample assessed for conventional expertise. For each individual, 2000 metaphases were scored for the presence or absence of reciprocal and terminal translocations. We present here a comparison between the results obtained by the two technologies for each of the cases studied separately. We describe their similarities or differences and discuss the suitability of using FISH painting for routine expertise analysis.

Chromosome Aberrations↗
PubMed1997

Intravenous 1,25(OH)2D therapy increases the intact parathyroid hormone secretion set point in hemodialyzed patients.

We have studied the effect of intravenous calcitriol [1,25(OH)2D] therapy (1 microgram at the end of each dialysis session) on parathyroid secretory curves of hemodialyzed patients with near-normal basal intact (< 10 pmol/l, n = 7; NNBI) or elevated basal intact (> 10 pmol/l, n = 6; EBI) parathyroid hormone (PTH; iPTH) levels. These results were compared with those obtained in matched normal individuals (N). Our main objective was to define the influence of intravenous 1,25(OH)2D therapy on the set point of iPTH stimulation in relation to the severity of secondary hyperparathyroidism. A complete parathyroid function was obtained by CaCl2 and Na2EDTA infusions in 14 N and by modification of the dialysate calcium content in 13 hemodialyzed patients. Ionized calcium (Ca2+) and iPTH were measured regularly during hypo- and hypercalcemia. Parathyroid secretory curves were derived from these data. Both groups of patients had lower basal Ca2+ (NNBI 1.16 +/- 0.05; EBI 1.10 +/- 0.03; N 1.25 +/- 0.04 mmol/l; p < 0.001) and higher basal iPTH (NNBI 6.3 +/- 2.5; EBI 49.2 +/- 39.5; N 2.5 +/- 0.8 pmol/l; p < 0.01) levels than N with more extreme values in EBI than in NNBI patients (p < 0.001). NNBI patients had stimulated iPTH levels similar to N (18.4 +/- 7.1 vs. 17.3 +/- 7.2 pmol/l), while these levels were markedly increased in EBI patients (80.7 +/- 46.0 pmol/l; p < 0.001). After 1,25(OH)2D therapy, Ca2+ increased to 1.16 +/- 0.03 mmol/l in EBI and normalized in NNBI patients (1.25 +/- 0.07 mmol/l). Stimulated iPTH decreased by 30% in NNBI (p < 0.05) and by 21% in EBI patients (NS). These two factors contributed to a decrease in basal iPTH by 52% in NNBI (p < 0.05) and by 40% in EBI (p < 0.01). The set point of iPTH stimulation was lower than in N (1.18 +/- 0.04 mmol/l) and increased with intravenous 1,25(OH)2D therapy from 1.09 +/- 0.03 to 1.16 +/- 0.05 mmol/l in NNBI (p < 0.05) and from 1.08 +/- 0.04 to 1.12 +/- 0.04 mmol/l in EBI patients (p < 0.05). The set points and changes in set point were correlated with basal Ca2+ (r = 0.56; p = 0.003) and changes in basal Ca2+ (r = 0.64; p = 0.04) observed before and during therapy. The starting position of each patient on his secretory curve before and after 1,25(OH)2D therapy was inversely related to his starting Ca2+ concentration (n = 26; r = -0.66; p = 0.0003). Taking this into account improved the relationship between Ca2+ concentration and the set point of iPTH stimulation by Ca2+ in a stepwise regression (R2 = 0.62; p = 0.0003). However, no correlation was found between set points and stimulated iPTH values. We concluded that 1,25(OH)2D therapy induced an increase in the set point of PTH stimulation in hypocalcemic hemodialyzed patients related to a similar increase in basal Ca2+ concentration. This is in part related to the starting position of each patient on his secretory curve which will affect his set point in relation to the hysteresis phenomenon in iPTH secretion. But the set point of PTH stimulation is also related to the basal ionized calcium concentration by mechanisms yet to be elucidated.

Adult↗