[Crossed eyes on arterial blood pressure in sitting position]. / L'image du mois. Regards croisés sur la pression artérielle en position assise.

Prolonged standing or even sitting position can induce a fall in arterial blood pressure because of gravity that provokes a blood volume sequestration in lower limbs. Such a phenomenon may be associated with orthostatic dizziness or sometimes syncope. We present the image of a continuous monitoring using a Finometer® of systolic blood pressure and heart rate. Crossing legs while in sitting position allows immediate increase of arterial blood pressure. This pathophysiological mechanism explains why numerous people cross legs in sitting position, for instance during a prolonged meeting, in an auditorium or in a movie theater. This common phenomenon has potential diagnostic, therapeutic and prognostic implications.

La position debout, ou même assise, prolongée peut entraîner une baisse de la pression artérielle compte tenu d'une certaine séquestration du volume sanguin dans les membres inférieurs due à la gravité, ce qui peut provoquer un malaise lipothymique, voire une syncope. Nous présentons l'image d'un enregistrement continu, avec un Finometer®, de la pression artérielle systolique et de la fréquence cardiaque, démontrant que le simple fait de croiser les jambes en position assise permet de faire remonter, quasi instantanément, la pression artérielle. Ce mécanisme physiopathologique explique pourquoi de nombreuses personnes croisent les jambes en position assise, que ce soit, par exemple, lors d'une réunion prolongée, dans un auditoire ou dans une salle de cinéma. Ce phénomène, a priori banal, a potentiellement des implications diagnostiques, thérapeutiques et pronostiques. Mots-clés : Pression artérielle - Hypotension - Position corporelle - Mesure continue - Finometer®.

Optimization of embryonic thermal programming confirms increased liver fattening in mule ducks and changes in lipid metabolism.

Introduction: The embryonic thermal programming (TM) in birds has been shown to impact several physiological parameters such as resistance to thermal stress, muscle growth or immunity. In mule ducks, it has recently been shown that TM can induce metabolic programming resulting in increased liver weight and fat storage after overfeeding. However, a decrease in hatchability and foie gras quality was also observed, suggesting that this technique needs to be optimized. Here, we tested a new thermal manipulation condition determined with the objective of avoiding negative impacts while maintaining or improving liver properties. Methods: The eggs of the control group were incubated at 37.6°C during the whole incubation period while those of the experimental group (TM group) were incubated at 39.3°C 16 h/24 h from the 11th day of incubation to the 21st. After hatching, all the animals were fed and raised under the same conditions until the age of 12 weeks. At this stage, one part of the animals was overfed and then slaughtered 2 h (to measure rapid changes in metabolism) or 10 h after the last meal (to obtain the best technological yields), while the other part was ration-fed and slaughtered 2 h after the last meal, at the same age. Results: An 8% increase in foie gras production was measured in the TM group compared to the control group without altering the quality of the final product (nor hatchability), confirming the successful optimization of the metabolic programming. Interestingly, these results allowed us not to reject the previously suggested hypothesis of a potential delay in metabolic processes involved in liver fattening in programmed animals, in particular by measuring a trend reversal regarding the amount of total hepatic lipids in both groups at 2 h and then 10 h after the last meal. Discussion: This study therefore validates the optimization of metabolic programming by embryonic thermal manipulation for duck liver fattening. The understanding of the mechanisms of embryonic thermal programming in birds remains today very incomplete and the search for epigenetic marks (main hypothesis of the concept of programming) at the origin of the observed phenotypes could be the next step of this work.

Substantiation of an artificial saliva formulated for use in a masticatory apparatus.

The aim of this work was to substantiate artificial saliva prepared for use in a masticator apparatus. Mastication's goal is to produce a viscous and plastic food bolus where these properties authorize a safe swallow. Apart from its biochemical contribution, saliva is mainly used in this kind of apparatus to provide a viscous component to the bolus. Artificial saliva was prepared with water and minerals, and completed with mucin and amylase. Different physico-chemical conditions were applied and the resultant viscosity was compared to that of human saliva. Mechanically- or chemically-stimulated salivas of ten healthy subjects were collected. Viscosity was measured with a capillary viscometer in response to changes in measurement's temperature, air exposure or pH. The effects of circadian saliva collection and the stimulation type on viscosity of human saliva were also studied. Viscosity of artificial and human salivas was comparable. An increase in the measurement's temperature or a 30 min-exposure of saliva to air led to a significant decrease in viscosity of both types of saliva. Amylase in artificial saliva did not change viscosity. The viscosity of human saliva displayed important subject variability as well as a dependence on the stimulation type of saliva production. This work allowed a useful evaluation of the formulated artificial saliva. It exhibited similar viscosity as the natural saliva in response to different methodological conditions. Therefore the proposed artificial saliva satisfies the major requirement of viscosity for a use in the masticator apparatus designed to prepare a food bolus.

Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. II. T lymphocyte-mediated cytolysis.

Tumor cell variants that were rejected by syngeneic mice (tum-) were obtained from mastocytoma P815 by mutagenesis (as described in the accompanying report (13). A considerable T lymphocyte-mediated lysis was observed upon incubation of these tum- variants with peritoneal exudate cells collected a few days after an intraperitoneal challenge of immune animals. Spleen cells from these animals were cytolytic after stimulation in vitro with the immunizing variant. New antigens, absent from the original P815 tum+ cells, were detected on 15 of the 21 tum- variants that were tested. All these antigens appeared to be different. No new antigen was detected on any of 10 mutagenized P815 clones that had retained their ability to form tumors. We compared the evidence obtained in vivo and in vitro for the presence of specific antigens on five tum- variants. Three variants were shown both in vivo and in vitro to carry an individual antigen. One showed no specificity either in vivo or in vitro. However, for one variant, no specificity was observed in vivo, although cytolysis tests demonstrated the existence of a singular antigenic specificity.

Changes in pulse pressure, heart rate and the pulse pressure x heart rate product during squatting in Type 1 diabetes according to age.

AIMS: We assessed changes in pulse pressure and heart rate during a squatting test, as indirect markers of arterial stiffness and cardiovascular autonomic neuropathy, respectively, according to age and sex in patients with Type 1 diabetes mellitus. METHODS: We evaluated 160 diabetic patients, divided into four groups of 20 men and 20 women according to age (G1, 20-30 years old; G2, 31-40 years old; G3, 41-50 years old; and G4, 51-60 years old), and 160 non-diabetic matched control subjects. Each subject underwent a 3 min posture test (standing-squatting-standing) with continuous measurement of arterial blood pressure and heart rate by a Finapres device. Overall values throughout the test, baseline levels in initial standing position and squatting-induced changes in pulse pressure, heart rate and the pulse pressure x heart rate product were compared between diabetic patients and healthy control subjects. RESULTS: In the standing position, a greater increase in pulse pressure and lower reduction in heart rate with age led to a significantly higher pulse pressure x heart rate product in diabetic patients compared with control subjects. In the squatting position, a more marked pulse pressure increase in the absence of appropriate reduction in heart rate resulted in a greater rise in the pulse pressure x heart rate product in diabetic patients than in healthy subjects. No major differences were noted between the sexes, with the exception of a stronger relationship between pulse pressure and age in the female population with diabetes. Squatting-derived indices of cardiovascular autonomic neuropathy were also noted with increasing age in diabetic patients. CONCLUSIONS: The marked increase in the pulse pressure x heart rate product ('pulsatile stress') according to age, combined with cardiovascular autonomic neuropathy, may contribute to the higher cardiovascular risk of patients with Type 1 diabetes.

Pancreatic hypoplasia presenting with neonatal diabetes mellitus in association with congenital heart defect and developmental delay.

Congenital pancreatic hypoplasia is a rare cause of neonatal diabetes. We report on a series of three patients with pancreatic agenesis and congenital heart defects. All had abdominal scan evidence of pancreatic agenesis. In addition, Patient 1 had a ventricular septal defect, patent ductus arteriosus and pulmonary artery stenosis; Patient 2 had a truncus arteriosus and Patient 3 had tetralogy of Fallot. Two of the three patients have developmental delay. All three patients were isolated cases within the family. Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found. Genetic investigation to exclude paternal UPD 6, methylation aberrations and duplications of 6q24 was also negative in all three. 22q11 deletion was excluded in all three patients. Array CGH in Patient (1) showed a approximately 250 kb, paternally inherited duplication of chromosome 12q [arr cgh 12q24.33 (B35:CHR12:131808577-132057649++) pat], not found in the other two patients. Permanent neonatal diabetes mellitus due to pancreatic hypoplasia with congenital heart defects has been reported before and may represent a distinct condition. We discuss this rare association and review previously reported literature.

Supporting the recommended paediatric dosing regimen for rufinamide in Lennox-Gastaut syndrome using clinical trial simulation.

Rufinamide was approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) as adjunctive therapy in patients aged 4 years and older. Rufinamide pharmacokinetics (PK) has been established on pooled data from several clinical studies in epilepsy, including one in LGS patients. Demographic covariates and drug-drug interactions with several antiepileptic drugs have been explored using population PK modelling. Two types of drug-drug interactions models were developed and compared. The PK analysis demonstrated that the coadministration of valproate decreases rufinamide clearance, requiring potential dose adjustment. To explore rufinamide exposure under different dosing regimens in LGS patients, clinical trial simulations were performed. The objective of the simulations was to select the doses giving an exposure shown to be safe and efficacious in larger populations. The concentrations simulated in a subgroup of patients with body weight less than 30 kg presented a larger inter-individual variability than in other patients. Additional simulations demonstrated that this increased variability was due partly to greater valproate concentrations in some of the children treated with rufinamide. Simulations of the rufinamide exposure under different maximum daily dose in presence and in absence of valproate co-administration were used to establish the dosing recommendation. The simulations support the proposal of a lower maximum daily rufinamide dose for patients under 30 kg receiving both drugs: the dose of 600 mg/day was proposed as a maximum daily dose in children also receiving valproate concomitantly, whereas in absence of valproate, the maximum daily dose is 1000 mg/day.

Pulse pressure and cardiovascular autonomic neuropathy according to duration of type 1 diabetes.

BACKGROUND: To evaluate changes in pulse pressure (PP) and markers of cardiovascular autonomic neuropathy (CAN) according to duration of type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional controlled study evaluated 159 diabetic patients during a 3-min posture test (standing-squatting-standing) with continuous measurement of systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure by a Finapres device. Arterial stiffness was indirectly assessed by PP and the slope of PP as a function of MBP calculated during the whole 3-min test. CAN was assessed by the expiration/inspiration pulse interval ratio (E/I R-R ratio) during deep breathing and by three indices measured during the squatting test. Patients were divided into four groups according to diabetes duration (<10 years, 11-20 years, 21-30 years and > 30 years from group 1 to group 4, respectively) and compared with age-matched non-diabetic subjects. RESULTS: PP progressively increased (p < 0.0001) and PP/MBP decreased (p < 0.0005) according to T1DM duration, whereas these parameters remained almost unchanged in age-matched control subjects. E/I ratio (p < 0.0001) and baroreflex gain (p < 0.0005) progressively decreased with T1DM duration. The parasympathetic index (squatting test vagal ratio-SqTv) significantly increased (p < 0.0001), whereas the sympathetic index (squatting test sympathetic ratio-SqTs) only tended to decrease (p = 0.12) according to diabetes duration. No such changes in CAN indices were observed in the non-diabetic population. CONCLUSIONS: PP increased according to T1DM duration in an age range where PP remained almost stable in controls, in agreement with accelerated arterial stiffening due to chronic hyperglycaemia. The baroreflex gain decreased and other indices of CAN also deteriorated with diabetes duration, more so indices reflecting parasympathetic rather than sympathetic dysfunction.

The fate of amoco cadiz oil.

The Amoco Cadiz oil spill (223,000 metric tons) of March 1978 is the largest and best studied tanker spill in history. Of the total oil lost, 30,000 tons (13.5 percent) rapidly became incorporated into the water column, 18,000 tons (8 percent) were deposited in subtidal sediments, 62,000 tons (28 percent) washed into the intertidal zone, and 67,000 tons (30 percent) evaporated. While still at sea, approximately 10,000 tons of oil were degraded microbiologically. After 3 years, the most obvious effects of the spill have passed, although hydrocarbon concentrations remain elevated in those estuaries and marshes that were initially most heavily oiled.

Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South Africa.

There is a need for sensitive bio-monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long-term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology-based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2.

[Sweat testing: review of technical requirements]. / Recommandations pour l'exécution et l'interprétation du test de la sueur.

The sweat test, a quantitative measurement of chloride in sweat, remains a key laboratory test to support the diagnosis of cystic fibrosis. However, because of its delicate execution, sweat test result should be interpreted with biological, clinical and genetic arguments. The following guidelines which we propose, were established in order to harmonize the practices of the sweat test. They are elaborated in a consensual way by biologists from cystic fibrosis reference centers and/or from the working group "Sweat Testing" of the National College of Biochemistry Hospital praticiens, according to the current state of knowledge on the subject, the experiment of the biologists and the recommendations established in the United States and in the United Kingdom.

Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma.

Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death-ligand 1 (PD-L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. This analysis based upon 906 patients from two phase I and one phase II MUC studies, is the first report of the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of atezolizumab. Atezolizumab exhibited linear PK over a dose range of 1-20 mg/kg, including the labeled 1,200 mg dose. The clearance, volume of distribution, and terminal half-life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days, respectively, were as expected for an IgG1. Exposure-response analyses did not identify statistically significant relationships with either objective response rate or adverse events of grades 3-5 or of special interest. None of the statistically significant covariates from PopPK (body weight, gender, antitherapeutic antibody, albumin, and tumor burden) would require dose adjustment.

[Arterial pulse pressure in relation to the duration of type 1 diabetes: a cross-sectional controlled study]. / Effets de la durée du diabète de type 1 sur la pression artérielle pulse: étude transversale contrôlée.

Diabetes mellitus and arterial pulse pressure (PP) are two independent cardiovascular risk factors. This cross-sectional study investigated the influence of diabetes duration on PP in type 1 diabetic patients without any cardiovascular disease. PP was measured continuously during 3 minutes (active orthostatic test: 1 min standing--1 min squatting--1 min standing) using a fingertip plethysmograph (Finapres) in 159 type 1 diabetic patients aged 20-60 yrs. They were divided into 4 groups according to diabetes duration: (1) G1 : <10 yrs (n=39); G2: 11-20 yrs (n=45); G3: 21-30 yrs (n=57); and G4: >30 yrs (n=18). In order to separate the effects of age from the effects of diabetes duration, diabetic patients were compared to age- and sex-matched non diabetic controls. PP (expressed in mmHg; mean +/- SD) was higher in men than in women in both diabetic (58 +/- 15 vs. 50 +/- 14; p = 0.001) and non diabetic subjects (55 +/- 14 vs. 47 +/- 12; p = 0.001). Overall PP was higher in diabetic than in non diabetic individuals (54 +/- 15 vs. 50 +/- 13; p = 0.025). PP progressively increased according to diabetes duration: 47 +/- 16 vs. 51 +/- 13 vs. 59 +/- 14 vs. 62 +/- 12, from G1 to G4 respectively; p < 0.0001. Such an increase was not observed in age-matched non diabetic subjects: 50 +/- 11 vs. 52 +/- 12 vs. 49 +/- 14 vs. 52 +/- 18, from G1 to G4, respectively; NS. PP was higher in squatting than in standing position in non diabetic subjects (52 +/- 16 vs. 47 +/- 13; p < 0.0001) and even more in diabetic patients (59 +/- 17 vs. 50 +/- 14; p < 0.0001). Overall, PP difference between diabetic and non diabetic individuals was not significant in standing position (50 +/- 14 vs. 47 +/- 13; NS) although it became highly significant in squatting position (59 +/- 17 vs. 52 +/- 16; p = 0.0005). The squatting-standing difference in PP markedly increased with diabetes duration: 69 +/- 14 during squatting vs. 50 +/- 18 during standing in G4 compared to respectively 50 +/- 17 vs. 44 +/- 15 in G1 diabetic patients. Finally, PP was similar (NS) in diabetic patients with HbA1c < 8% (54 +/- 14) or > or =8% (55 +/- 16), with (57 +/- 17) or without (54 +/- 14) microalbuminuria, treated (56 +/- 14) or not (54 +/- 15) by inhibitors of the renin-angiotensin system. In conclusion, PP progressively increased with the duration of type 1 diabetes, independently of age. Such increase was more marked in squatting than in standing position. The role of such PP rise in the increased cardiovascular risk of patients with type 1 diabetes, although suspected in the recent EURODIAB Prospective Complications Study, deserves further investigation.

[The role of aortic morphology in the occurrence of hypertension in patients undergoing surgery for coarctation of the aorta before the age of 1 year]. / Rôle de la morphologie aortique dans la survenue d'une hypertension artérielle chez des malades opérés d'une coarctation de l'aorte avant l'âge de 1 an.

OBJECTIVE: Hypertension on effort can be observed following surgical treatment of coarctation of the aorta even if the operation has been performed early and has been judged to be satisfactory. The pathophysiology of this hypertension has not been completely elucidated. The aim of our study was to look for a residual morphological anomaly of the aortic arch which might be responsible. METHODS: This was a retrospective study of patients aged over 10 years who had undergone surgery for coarctation of the aorta before the age of 1 year, consecutively between 1979 and 1993, and free from re-coarctation clinically or with Doppler. All of them had a blood pressure effort test on a cycling machine, echocardiography and an MRI of the thoracic aorta. RESULTS: 61 patients were included. Their median age was 15 years, 59% were male, 15% were hypertensive at rest and 56% on effort. With univariate analysis, only the average blood pressure (p=0.03) and the resting pulse pressure (p=0.001) were associated with hypertension on effort. With multivariate analysis the only factors that correlated independently with maximum arterial pressure on effort were the height of the patient (p=0.02) and the pulse pressure (p<0.0001). The surgical technique and the age at intervention were not associated with hypertension on effort (p=0.96 and 0.69 respectively). The diameter of the horizontal aorta and the aorta at the site of repair, measured on MRI, added to the diameter of the descending aorta at the diaphragm were not lower in patients with hypertension on effort (p=0.77 and 0.38). There were proportionally more Roman type aortic arches than Gothic types in patients with hypertension on effort, but this difference was not significant (p=0.18). CONCLUSION: In our study, the patients with hypertension on effort following correction of coarctation of the aorta did not display any residual obstruction at the level of the aortic cross on MRI. However, they had a resting pulse pressure that was significantly higher than the non hypertensive patients, reflecting an increase in the aortic wall rigidity.

[Quality of life of patients with total cavopulmonary anastomosis]. / Qualité de vie des patients avec une dérivation cavo-pulmonaire totale.

INTRODUCTION: Total cavo-pulmonary connection (TCPC) represents the current surgery standard for congenital univentricular heart disease (CUHD) patients. We studied the health related quality of life (HRQOL) expressed by TCPC operated patients. PATIENTS AND METHODS: This transversal study is based on 24 children and 10 adult TCPC patients aged from 5 to 41 years old. The HRQOL evaluation relies on generic self report instruments such as the PedsQL 4.0 for the children and their parents, and the Duke Health profile for the adult patients. Additional questions were specifically designed for this study as well. RESULTS AND DISCUSSION: The estimated HRQOL is 68.15 for the children and 68.71 for their parents. In these young cases, the global HRQOL or some specific score are altered when any comorbidity or scholar difficulties are present, or when TCPC was performed more than 10 years ago. The estimated HRQOL is 74.67 in adulthood. In these patients, the young age, the lifestyle, the onset of more than 2 early complications ans the necessity of anti-arrhythmia therapy decrease various HRQOL scores. The physical handicap is considered as the major limitation for children and adult patients. Thanks to adaptative and cognitive compensatory mechanisms, such as resilience, both groups express a satisfying HRQOL assessment. CONCLUSION: Our study indicates that TCPC provides a good HRQOL in CUHD patients despite the complex management and follow-up of these diseases, the risk of complication onset and the physical handicap usually observed.

Susceptibility to acidification of groundwater-dependent wetlands affected by water level declines, and potential risk to an early-breeding amphibian species.

Eggs of the Western spadefoot toad (Pelobates cultripes) reached a 100% mortality in all 29 clutches deposited at a pH below 5.0 in a temporary pond of the Doñana National Park (SW Spain) throughout the wet season of 2006-2007. A similar trend was detected in a neighbouring pond. The proximity of these two ponds to a groundwater pumping area (<1.5km), prompted us to elucidate the possible links between the reduction in pond hydroperiod over past decades (1989-2008) and the decrease of groundwater pH-buffering capacity. The average hydroperiod had decreased by 4months since 1998-99 in the pond where the extensive egg mortality had occurred. The total alkalinity, and the Mg(2+)concentration had also significantly declined in the shallow water-table since 1998-99, from an average of 8.56 to 0.32meql(-1), and of 3.57 to 1.15meql(-1), respectively. This decline of the shallow groundwater buffering capacity could turn this pond more susceptible to the inorganic acidity associated with pyrite oxidation as the sediment S content was often above 0.03%. The initial ratio of S/Ca+Mg in the summer dry sediment was a good predictor of pore-water pH on re-wetting after desiccation (r(2)=0.802, p<0.01). Therefore, this ratio can give some anticipation to mitigate the impact of acidity on toad hatching before these temporary ponds are reflooded on the next wet season. Our results suggest that the long-term damage to pond water levels can trigger a potential risk of soil acidification in the presence of iron-sulphide minerals.

[Evaluation after 20 years of a case of Takayasu's disease that presented with aortic regurgitation]. / Evolution après 20 ans d'une maladie de Takayasu Révélée par une insuffisance aortique.

Takayasu's disease is a segmental multifocal affection of medium and large arteries. The diagnosis is based on the association of stenotic and aneurismal lesions of the aorta and its branches secondary to an inflammatory infiltration of the media and adventitia. Cases of aortic regurgitation associated with aneurismal dilatation of the ascending aorta as the presenting features of Takayasu's disease, as in this case, are rare. Histological examination of the aortic wall may help establish the diagnosis by showing signs of aortitis. The other usual arterial lesions are sometimes missing at the initial phase of the disease. A late histological diagnosis may be difficult as the inflammatory lesions tend to be progressively replaced by fibrotic lesions or a banal atheroma.

[Diabetic cardiac autonomic neuropathy]. / La neuropathie autonome cardiaque diabétique.

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes mellitus, which is associated with a higher risk of morbidity and mortality. It can be detected by analyzing spontaneous (Holter) or provoked (Ewing's test battery) changes in heart rate and arterial blood pressure. Baroreflex gain is a specific index of great interest. Our laboratory has acquired a large experience in the assessment of CAN in diabetic patients. We use the Finapres, a device that allows continuous noninvasive monitoring of blood pressure and heart rate, and a special and discriminative active orthostatic manoeuvre, the "squatting" test (standing-squatting-standing).

Partial deletion of the AGXT gene (EX1_EX7del): A new genotype in hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal (2q37.3) recessive metabolic disease caused by a deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate amino transferase. Molecular heterogeneity is important in PH1 as most of the patients (if the parents are unrelated) are compound heterozygotes for rare mutations. We describe the first large deletion in the AGXT gene, removing exons 1 to 7 (EX1_EX7del) that was responsible for one case of severe PH1. This 10 kb deletion was identified by Southern blotting of genomic DNA digested by Xba I and hybridized with different exonic probes. Both parents (from Turkey) are first cousin and carry the deletion. It is of note that the presently reported patient did not exhibit any AGT catalytic activity and even so, he progressed towards end-stage renal disease only at 19 years old.