Doppler Flow Wire Evaluation of Renal Blood Flow Reserve in Hypertensive Patients with Normal Renal Arteries

Purpose: To study the vasomotor responses of the renal microcirculation in patients with essential hypertension. Methods: We studied the reactivity of the renal microcirculation to papaverine, with intraarterial Doppler and quantitative arteriography, in 34 renal arteries of 19 hypertensive patients without significant renal artery stenosis. Isosorbide dinitrate was given to maximally dilate proximal renal arteries. APV (average peak blood flow velocity) was used as an index of renal blood flow. Results: Kidneys could be divided into two distinct subgroups based on their response to papaverine. An increase in APV of up to 55% occurred in 21 kidneys, an increase > 55% in 13 kidneys. Within each group the values were normally distributed. Both baseline APV and the effect of papaverine on mean velocity differed significantly between groups. Conclusion: There seems to be a subgroup of patients with essential hypertension that has an impaired reactivity to papaverine, consistent with a functional impairment of the renal microcirculation. Further studies are required to determine whether this abnormality contributes to or results from elevated blood pressure.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

High Pressure (HP) in Spark Plasma Sintering (SPS) Processes: Application to the Polycrystalline Diamond

High-Pressure (HP) technology allows new possibilities of processing by Spark Plasma Synthesis (SPS). This process is mainly involved in the sintering process and for bonding, growing and reaction. High-Pressure tools combined with SPS is applied for processing polycrystalline diamond without binder (binderless PCD) in this current work. Our described innovative Ultra High Pressure Spark Plasma Sintering (UHP-SPS) equipment shows the combination of our high-pressure apparatus (Belt-type) with conventional pulse electric current generator (Fuji). Our UHP-SPS equipment allows the processing up to 6 GPa, higher pressure than HP-SPS equipment, based on a conventional SPS equipment in which a non-graphite mold (metals, ceramics, composite and hybrid) with better mechanical properties (capable of 1 GPa) than graphite. The equipment of UHP-SPS and HP-SPS elements (pistons + die) conductivity of the non-graphite mold define a Hot-Pressing process. This study presents the results showing the ability of sintering diamond powder without additives at 4–5 GPa and 1300–1400 °C for duration between 5 and 30 min. Our described UHP-SPS innovative cell design allows the consolidation of diamond particles validated by the formation of grain boundaries on two different grain size powders, i.e., 0.75–1.25 μm and 8–12 μm. The phenomena explanation is proposed by comparison with the High Pressure High Temperature (HP-HT) (Belt, toroidal-Bridgman, multi-anvils (cubic)) process conventionally used for processing binderless polycrystalline diamond (binderless PCD). It is shown that using UHP-SPS, binderless diamond can be sintered at very unexpected P-T conditions, typically ~10 GPa and 500–1000 °C lower in typical HP-HT setups. This makes UHP-SPS a promising tool for the sintering of other high-pressure materials at non-equilibrium conditions and a potential industrial transfer with low environmental fingerprints could be considered.     

Effect of the duration of immunomodulatory therapy on the clinical features of recurrent episodes in Vogt–Koyanagi–Harada disease

Purpose: To evaluate the duration of immunomodulatory therapy (corticosteroids, immunosuppressive drugs) with regard to the rate of relapses and clinical features (exudative retinal detachment or anterior uveitis) in inflammatory episodes of Vogt–Koyanagi–Harada disease. Methods: Data of all 42 patients diagnosed with acute uveitis associated with VKH disease during the period of January 2005 to December 2008 at the Pitié‐Salpêtrière Hospital or at the Lariboisière Hospital in Paris, France were extracted by chart review. Results: There were 31 patients (73.8%) with episodes of recurrence and were included in the study. At the first recurrence, 81% (13 patients) of exudative retinal detachments (ERD) were associated with an initial immunomodulatory treatment conducted ≤6 months (3.76 months ± 2.67). Conversely, an initial treatment duration of >6 months was associated with anterior uveitis signs for 66% of patients (eight patients) with anterior first recurrence (p = 0.0061). On second episode of recurrence, 75% of patients (three patients) who developed exudative retinal detachment had been managed by immunomodulatory therapy for ≤6 months with the total duration of immunomodulatory treatment ≤6 months during previous inflammatory episodes. Conversely, all 16 patients who presented anterior uveitis with additional manifestations (optic disc oedema, macular oedema, vitritis and/or ‘Sunset glow’ fundus) have been treated for more than 6 months or treated during the initial occurrence lasting more than 9 months (p = 0.0035). Conclusions: The duration of systemic corticosteroids (and/or immunosuppressive drug therapy) for ≤6 months at first and second recurrence was associated with features of further exudative retinal detachment instead of anterior uveitis in VKH disease.     

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. METHODS: The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. RESULTS: (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. CONCLUSION: The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.     

Does malignant fibrous histiocytoma exist?

Malignant fibrous histiocytoma (MFH) has come to be regarded as the most common malignant neoplasm of the mesenchymal soft tissues. It designates a spectrum of tumors which share morphologic features that allow their inclusion in a distinct clinicopathologic setting, although being not uniform in their histogenesis and pathogenesis. Clinicopathologic variants include the following: the storiform-pleomorphic form of MFH, the myxoid type of MFH, the giant cell type of MFH and the inflammatory type. The latter group, the angiomatoid variant, has been reclassified within the fibrohistiocytic tumors of low malignant potential. Tissue culture, ultrastructural and immunohistochemical studies have both endorsed or refuted the validity of the concept. As a whole, these morphologic studies which attempted to characterize MFH were not able to delineate specific markers or to describe the phenotype of this sarcoma of supposed fibrohistiocytic lineage. There is growing evidence that MFH is a second component in another sarcoma and represents a morphologic modulation resulting from tumor progression. Recent cytogenetic and molecular genetic investigations are consistent with that hypothesis: a comparative analysis between the most frequent genomic imbalances observed in series of MFH and leiomyosarcomas (LMS) demonstrated that both tumors had similar recurrent imbalances. Immunohistochemical and molecular biologic investigations have shown similar targets of chromosome deletions in both tumors. A new classification of soft tissue sarcoma based on molecular parameters is nevertheless premature. The morphologic characterization of MFH and its sub-types provides the clinician with unique information in the management of these tumors, by identifying a spectrum of tumors with well-recognized clinical profiles.     

Acute bacterial meningitis at the 'Complexe Pédiatrique' of Bangui, Central African Republic

To precis the aetiologies of children meningitis and the susceptibility to antibiotics of bacteria responsible for meningitis in Bangui, we conducted a prospective study between October 2004 and September 2005, at the 'Complexe Pédiatrique de Bangui', Central African Republic (CAR). Children from 1 day to 16 years with suspected meningitis and who underwent a lumbar puncture were enrolled. Gram staining, culture on chocolate blood medium, cell count, biochemistry (protein level, glucose ratio), capsular antigen detection were performed for each cerebrospinal fluid. MICs were determined by the E-test method. Four hundred and seventeen patients were enrolled during the study period; 130 were proven acute bacterial meningitis and 37 probable bacterial meningitis. Among proven bacterial meningitis, Streptococcus pneumoniae was the most common organism responsible for meningitis (62 cases, 48%) followed by Haemophilus influenzae (46 cases, 35%) and by Neisseria meningitidis and Salmonella sp. (8 cases, 6% each). Ninety-four percent and 96% of S. pneumoniae strains tested remain susceptible to benzylpenicilline and chloramphenicol, respectively. A beta-lactamase was detected in 92% of H. influenzae strains tested. However, MICs 50% and 90% for amoxicillin were found to be 1 and 4 mg/l, respectively and 33% of these strains were resistant to chloramphenicol. The global mortality rate was 35% (59/167). This mortality rate was 47% for S. pneumoniae, 33% for H. influenzae, 62% for Salmonella sp. and 13% for N. meningitidis. The probabilistic treatment with ampicillin and chloramphenicol usually administered for children meningitis in Bangui must be reconsidered particularly in cases of H. influenzae meningitis. It is of importance to reduce the presentation delays of children with suspected meningitis in Bangui. The H. influenzae b immunization would allow a dramatic reduction of meningitis cases and deaths in Central African children.