Identification of a novel mutation, 1087delT, in exon 7 of the CFTR gene in a patient with cystic fibrosis.
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Adolescent↗
Biomedical subjects
M Guillot
Publications and source records attributed to M Guillot.
Gelatinase isoforms in urine from bladder cancer patients.
Matrix metalloproteinases are involved in tumor invasion and metastasis in many types of human carcinomas, in leukocyte infiltration and inflammatory reactions. Three metalloproteinases with gelatinolytic activity were isolated from the urine of patients with untreated high grade bladder cancer or with functioning renal grafts (control). Urinary proteins were fractionated after concentration by continuous-elution SDS-polyacrylamide gel electrophoresis. Collected fractions were analyzed by gelatin zymography and Western blotting. The one-step purification process isolated the gelatinase species from crude urine samples: (1) a 72 kDa progelatinase A (MMP-2) and its actived 68 kDa form; (2) a 92 kDa progelatinase B (MMP-9); (3) a higher molecular weight (HMW) complex (115 kDa) which was identified as progelatinase B associated with lipocalin, NGAL. A similar marker profile was observed in bladder cancer tissues. The current study demonstrated the efficiency of continuous elution electrophoresis. It offered two main advantages: (1) the separation of latent from active gelatinase isoforms with no interference from the TIMPs and (2) the identification and isolation in a single step of large amounts of urine gelatinase species with both high recovery and significant specific activities. Continuous-elution electrophoresis can be used for correlation with clinical events of bladder cancer diagnosis and prognosis.
Blotting, Western↗
[Macrolides and Pseudomonas aeruginosa infection].
Several unique effects of subinhibitory concentrations of C14 and C15 macrolides on Pseudomonas aeruginosa infection are described in vitro: P. aeruginosa virulence factors inhibition, bacterial biofilm disruption, P. glycoprotein expression upregulation, anti-inflammatory and immunoregulatory effects. Clinical trials in vivo are warranted to assess the potential usefulness of macrolides for treatment of chronic infections caused by P. aeruginosa.
Anti-Bacterial Agents↗
Cytotoxic effects of topotecan combined with various active G2/M-phase anticancer drugs in human tumor-derived cell lines.
Topotecan (TPT) is a DNA-Topoisomerase I poison that exhibits antitumor activity. TPT, like other DNA-damaging agents, arrests or delays cell cycle progression during S- and G2-phase in a wide variety of tumor-derived cell lines. Particularly, the G2-arrest gives time for the cell to repair its DNA lesions prior to starting a new cell cycle. Based on these observations, we assessed the interaction between TPT and G2/M-active agents in p53-mutated cell lines of diverse origin in order to achieve cell toxicity. Two short-term sequential schedules were administered (TPT --> G2/M-active drug at the interval of greatest TPT-induced G2/M-phase cell arrest, and G2/M-active drug --> TPT), in three human tumor-derived cell lines with proven sensitivity to the following drugs: Bleomycin in HEp-2 (squamous larynx carcinoma); Docetaxel in SKBr-3 (breast adenocarcinoma); Etoposide in NCI-H23 (non-small-cell lung cancer). Our results show that: 1) Sequential TPT --> G2/M-active drugs are synergistic when administration overlapped the maximum percentage of TPT-induced G2/M-phase cell arrest interval in all three mutated p53 cell lines; 2) the reverse sequential schedule (G2/M-active drug --> TPT) was antagonistic, and being only additive for Etoposide --> TPT association. In conclusion, our findings further support the potential cytotoxic role of TPT in combination with other active drugs when the correct schedule of administration is applied. In addition, they provide a rationale for new applications in clinical trials using short-term sequential TPT --> G2/M-active drugs.
Antibiotics, Antineoplastic↗
Widely meshed autograft associated with cultured autologous epithelium for the treatment of major burns in children: report of 12 cases.
This is a retrospective study of the combination of widely meshed autograft and autologous cultured keratinocytes. We used this method faced with the lack of allogenic skin, as an alternate to the Cuono method. Twelve children suffering extensive burn injury (deep burns of 60%+/-16 of the total body surface) underwent this grafting procedure. The surgical treatment consisted of an early surgical excision, with an immediate coverage by autografts as much as possible. When cultured epithelium was available, a large mesh autograft was applied and covered with cultured epidermis sheets during the same operative procedure. The rate of take was of 84% (+/- 12). No secondary graft loss was observed. This means of coverage appeared reliable and resistant. On average, this method allowed the epidermization of 30% (+/-9) of the total body surface of the children. The average hospital stay of the children was 64+/-20 days. All the children recovered to lead a normal life. The school delay after rehabilitation is one year. This technique is an alternative to Cuono's method when allografts are missing. The combination of autograft and autologous cultured epidermis sheets appeared more effective than one of these techniques applied alone, as if the suggested coupling induced a synergy.
Adolescent↗
The burden of disease among the global poor.
BACKGROUND: Global and regional estimates show that non-communicable diseases in old age are rising in importance relative to other causes of ill health as populations age, and as progress continues against communicable diseases among infants and children. However, these estimates, which cover population groups at all income levels, do not accurately reflect conditions that prevail among the poor. We estimated the burden of disease among the 20% of the global population living in countries with the lowest per capita incomes, compared with the 20% of the world's people living in the richest countries. METHODS: Estimates for the global poorest and richest 20% were prepared for 1990 for deaths and disability-adjusted life years (DALYs), by a procedure used in a prominent recent study of the global disease burden. Projected mortality rates in the year 2020 were established for the world's poorest and richest 20% under various assumptions about the future rate of decline in communicable and non-communicable diseases. FINDINGS: In 1990, communicable diseases caused 59% of death and disability among the world's poorest 20%. Among the world's richest 20%, on the other hand, non-communicable diseases caused 85% of death and disability. A raised baseline rate of communicable disease decline between 1990 and 2020 would increase life-expectancy among the world's poorest 20% around ten times as much as it would the richest 20% (4.1 vs 0.4 years). However, the poorest 20% would gain only around a quarter to a third as much as the richest 20% from a similar increase in non-communicable diseases (1.4 vs 5.3 years). As a result, a faster decline in communicable diseases would decease the poor-rich gap in 2020, but under an accelerated rate of overall decline in non-communicable diseases, the poor-rich gap would widen. INTERPRETATION: Our estimates are crude, but despite their limitations, they give a more accurate picture of changes in attributable mortality among the world's poor than do the global averages in current use.
Global Health↗
Role of hip abduction in the kinetics of the thoracic and lumbar spine.
The motion of the thoracic and lumbar spine segments was analysed by mean of the skin landmarks method in 14 volunteers (7 males, 7 females). The results demonstrated that there was no significant difference between men and women and there was either facilitation or limitation of the motion of the characteristic landmarks of spinal segments during trunk motion in perpendicular planes. The mobility of spinal segments was associated with pelvic girdle motion in order to obtain the planned amplitude, and varied with hip joint abduction. The analysis of the precise mechanisms of relaxing or stretching of the pelvivertebral musculo-ligamentous structures constitutes a large field of investigation that necessitates the study of other lower limb postures and the use of robotic techniques.
Adult↗
[Cardiac involvement during classic hemolytic uremic syndrome].
BACKGROUND: Cardiac involvement rarely occurs in classic hemolytic uremic syndrome (HUS); it is often fatal. CASE REPORTS: The first patient, a 21-month-old boy, developed classic HUS with acute renal failure. Peritoneal dialysis was performed for 20 days. On the 10th day of dialysis, myocardial infarction occurred, probably related to coronary thrombus. The patient was given heparin and antibiotics because of an unexplained fever. The outcome was favorable despite antero-apical cardiac necrosis, and moderated chronic renal failure. The second patient, a 24-month-old girl, also showed a classic HUS, which required peritoneal dialysis for 10 days. Dilated cardiomyopathy with cardiac failure appeared on the 4th day of dialysis, not related to the volume overload and metabolic consequences of the acute renal failure, such as systemic hypertension or ineffective dialysis. On the 5th day of dialysis neurological involvement appeared. Neurological, cardiac and renal outcome was favorable. The third patient, a 25-month-old girl, developed a classical HUS, requiring peritoneal dialysis for 25 days. No cardiac insult appeared during the acute phase of the disease. After dialysis, the child had chronic renal failure (creatinine clearance: 15 mL/min/1.73 m2). Dilated cardiomyopathy appeared 3 months later, without definite etiology. The outcome was favorable with digoxin treatment. CONCLUSION: A cardiac involvement should also be searched for in the acute phase of HUS and several months later.
Acute Kidney Injury↗
Effects of true density, compacted mass, compression speed, and punch deformation on the mean yield pressure.
Compressibility properties of pharmaceutical materials are widely characterized by measuring the volume reduction of a powder column under pressure. Experimental data are commonly analyzed using the Heckel model from which powder deformation mechanisms are determined using mean yield pressure (Py). Several studies from the literature have shown the effects of operating conditions on the determination of Py and have pointed out the limitations of this model. The Heckel model requires true density and compacted mass values to determine Py from force-displacement data. It is likely that experimental errors will be introduced when measuring the true density and compacted mass. This study investigates the effects of true density and compacted mass on Py. Materials having different particle deformation mechanisms are studied. Punch displacement and applied pressure are measured for each material at two compression speeds. For each material, three different true density and compacted mass values are utilized to evaluate their effect on Py. The calculated variation of Py reaches 20%. This study demonstrates that the errors in measuring true density and compacted mass have a greater effect on Py than the errors incurred from not correcting the displacement measurements due to punch elasticity.
Pressure↗
Bilateral decrease in interictal hippocampal blood flow in unilateral mesiotemporal epilepsy.
OBJECT: The goal of this study was to determine whether regional cerebral blood flow (rCBF) changes that were found contralaterally to a verified unilateral epileptic focus were associated with the spatiotemporal organization of epileptic abnormalities. METHODS: The CBF in both hippocampi was assessed using stable Xe-enhanced computerized tomography in a series of 19 patients with unilateral mesiotemporal epilepsy. Results were compared according to the distribution of interictal spiking and the spatiotemporal organization of the ictal discharges as determined by stereoelectroencephalography. Two groups were defined: in Group 1 (nine patients), the discharge remained unilateral; in Group 2 (10 patients), the discharge spread to contralateral mesiotemporal structures. For Group 1, the rates of ipsi- and contralateral hippocampal blood flow (HBF) were 32.88+/-15.53 and 45.88+/-17.19 ml/100 g/minute, respectively, whereas in Group 2 they were 36.7+/-11.54 and 36.4+/-11.27 ml/100 g/minute (mean+/-standard deviation). A two-way analysis of variance combining type of seizure (Group 1 compared with Group 2) and HBF (ipsi- compared with contralateral absolute values) demonstrated a main effect for HBF (F[1,17] = 5.051; p = 0.0382), a significant interaction between the two factors (F[1,17] = 6.188; p = 0.0235), and no main effect for type of seizure (F[1,17] = 0.258; p = 0.6178). CONCLUSIONS: In unilateral mesiotemporal epilepsy, asymmetrical interictal hippocampal perfusion was correlated with restricted unilateral ictal discharges, whereas bilateral hippocampal hypoperfusion was correlated with ictal discharges spreading to the contralateral mesiotemporal structures. The lack of correlation between the degree of hypoperfusion and the percentage of neuron cell loss indicated that the decrease in rCBF has both functional and lesional origins.
Adolescent↗
Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis.
Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.
Cations↗
Genetic susceptibility associated with rare HRAS1 variable number of tandem repeats alleles in Spanish non-small cell lung cancer patients.
The highly polymorphic HRAS1 variable number of tandem repeats (VNTR), which maps 1 kb downstream from the human H-ras1 gene, has been described as an inherited predisposing factor in many human cancers. Here, we investigated the association between the presence of rare HRAS1 minisatellite alleles and lung cancer in the population studied. Four hundred sixty-six HRAS1 VNTR alleles from 233 lung cancer patients and 892 alleles from 446 unaffected controls were typed using PCR-long agarose gel electrophoresis assay of peripheral blood lymphocyte DNA. Rare alleles were differentiated from common alleles (a1, a2, a3, and a4) by shifts in electrophoretic mobility. Odds ratio was calculated to evaluate increased risk of lung cancer associated to the presence of rare HRAS1 alleles. A higher percentage of rare HRAS1 VNTR alleles in lung cancer patients than in unaffected controls (32.7 versus 21.9%) was confirmed. The presence of rare alleles was associated with an increased risk of lung cancer (odds ratio = 1.68; P < or = 0.0001), indicating a genetic predisposition to lung cancer. No differences based on other clinicopathological variables were observed. Furthermore, a meta-analysis showed a higher distribution of rare alleles in our study of Caucasian Spaniards than was found in other studies of American and Northern European Caucasian populations. We conclude that the presence of rare HRAS1 VNTR alleles may be an inherited predisposing factor in lung cancer. This presence can be easily determined from peripheral blood samples by PCR-based methods. Furthermore, interracial variations in allele frequencies and variations between Caucasian subpopulations suggest that genetic variations may be involved in susceptibility to lung oncogenesis, especially in certain ethnic populations.
Alleles↗
[Abduction of pelvic members and pelvic girdle kinematics].
The analysis of the displacement of the pelvic girdle, during movements of the trunk in the anatomical orthogonal plans, was carried out by the technique of the cutaneous markers on two series of 7 male subjects and 7 female. The photographs made it possible to objectify angular displacements of reliable singular points and to observe that the abduction of hips determines, according to movements carried out, either a facilitation, or a limitation of displacements observed similar in the two series. The precise mechanism of these variations will have to be analyzed by later studies.
Adult↗
[Secondary kidney amyloidosis and mucoviscidosis].
BACKGROUND: Due to the improvement in cystic fibrosis management, life expectancy has risen; on the other hand, longer survival has led to new complications, including secondary renal amyloidosis, which has been so far very uncommonly reported. CASE REPORTS: Secondary nephropathic amyloidosis was seen in two 25-year and 22-year-old adults with cystic fibrosis. Both had developed recurrent pulmonary infections due to Pseudomonas aeruginosa over several years. One patient died after 2 years of progressive kidney failure. CONCLUSION: Severe renal insufficiency due to secondary amyloidosis may complicate the course of cystic fibrosis and become the main prognosis factor in adults.
Adolescent↗
[Initial imaging in pediatric urinary tract infection].
First step imaging investigations in urinary tract infections in children rely upon conventional sonography, and, when available. Power Doppler sonography. Enhanced computerised tomography (CT) and dimercaptosuccinic acid (DMSA) scintigraphy are complementary investigations in difficult cases. Contrast cystourethrogram has always to be performed. Intravenous pyelography is no longer used as a first step imaging technique.
Child↗
Gelatinase concentration in tears of corneal-grafted patients.
PURPOSE: Gelatinolytic enzymes, which degrade type IV basement membrane collagen, have been shown to be expressed by corneal cells, either constitutively (gelatinase A or MMP-2) or after induction (gelatinase B or MMP-9). Our aim was to determine whether an enhanced MMP-9 and eventually MMP-2 concentration in tears could be evidenced in the case of corneal-graft failure. METHODS: The amount of MMP-2 and MMP-9 gelatinolytic enzymes was measured by quantitative zymography in tears of twenty-one controls (84 samplings) and in tears of twenty-three corneal-grafted patients in a one-year post-graft follow-up study. RESULTS: The mean MMP-2 values in controls were of 8.4 (+/-7.3) pg/10 micrograms protein and the mean MMP-9 values in controls were of 73 (+/-76) pg/10 micrograms protein. No active gelatinase form was detected in any of controls, but in all cases of corneal graft failure, the active forms of both enzymes were present, and enzyme concentrations were higher than control values. All patients had significantly higher MMP-9 values than controls at each sampling time (p < 0.0001). The "corneal-graft failure" patient group had statistically significant higher MMP-9 concentrations in tears than the "successful-graft" patient group at one month (p = 0.0312), four months (p = 0.0158) and one year (p < 0.01) after the graft. The presence of active MMP-9 was highly significant of graft failure four months and one year after the graft (p < 0.0001). In contrast, MMP-2 increase was delayed, with significantly higher MMP-2 values than controls in all patients at four months (p = 0.0231) and one year (p = 0.0001) after the graft, but MMP-2 values could not discriminate between patient groups. CONCLUSIONS: In our study, all cases of graft failure showed abnormally high levels of the active forms of metalloproteinase enzymes, and these values far exceeded the maximum control concentration. MMP-9 measurements in tears made between one and four months after corneal transplantation, and while local corticotherapy is steadily established, should help in predicting corneal graft rejection.
Adult↗
Determination of the position of the pelvic girdle using surface markers.
The overall movement of the trunk is made up of two components, namely the movements of the pelvic girdle and the vertebrae. In the frontal plane, the amplitude of the pelvic movements appears to be relatively limited compared to the vertebral column whereas the pelvis makes the major contribution to the total rotational movement in the axial plane.
Adult↗
The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux.
BACKGROUND: Sequential methods are particularly interesting when recruitment is difficult because they may allow a study to be stopped early while maintaining type I and II error rates. METHODS: This placebo-controlled, randomized double-blind study was aimed at assessing the efficacy of metoclopramide (0.2 mg/kg three times daily during 14 days) on gastroesophageal reflux in infancy. The main end point was the relative variation of the percentage of time at pH < 4 between inclusion (day 0) and evaluation (day 14) assessed on two 24-hour esophageal pH recordings. Statistical analysis was performed with use of a sequential method, the triangular test. RESULTS: The study was stopped after the seventh analysis (39 infants evaluated: 20 placebo and 19 metoclopramide) without showing the expected benefit. Improvement on the main end point was 30% +/- 48% (mean +/- SD). Corresponding unbiased median estimates were 22% for placebo and 39% for metoclopramide (p = 0.28, sequential analysis). On day 14, the percentage of time at pH < 4 was 8.1% +/- 11.7% for placebo and 6.7% +/- 9.2% for metoclopramide (p = 0.68, t test), and the number of reflux episodes > 5 minutes was 3.0 +/- 3.5 for placebo and 1.9 +/- 3.0 for metoclopramide (p = 0.33, t test). CONCLUSION: If a tendency for a superior improvement with metoclopramide than with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the corresponding single-stage design, the triangular test allowed to stop the study with a 15% reduction in sample size.
Antiemetics↗