A radioreceptor assay for quantitating plasma factor VIII/von Willebrand's protein

A sensitive and precise radioreceptor assay for determining plasma levels of human factor VIII/von Willebrand's factor (FVIII/vWF) has been developed by taking advantage of the FVIII/vWF receptor sites on human platelets. Paraformaldehyde-fixed platelets, which were processed and then stored, retained FVIII/vWF binding activity and therefore could be used as a convenient source of receptors. The human plasma samples to be tested were initially filtered on 4% agarose columns to concentrate the FVIII/vWF protein in the void volume and to remove the factor(s) that interferes with the assay. The percent recovery of FVIII/vWF in the pooled eluent was measured by the recovery of added trace 125I-FVIII/vWF. The coefficients of intra- and interassay variation were 6% and 10%, respectively. The plasma FVIII/vWF concentrations determined by the assay for pooled normal plasma, hemophilia A plasma, and plasmas from two patients with von Willebrand's disease were 16.3 +/- 0.5, 52.6 +/- 1.5, 6.8 +/- 0.8, and 3.2 +/- 0.2 microgram/ml, respectively. The range of plasma FVIII/vWF concentrations varied between 8.3 microgram/ml and 24.9 microgram/ml for 10 normal adults. The plasma FVIII/vWF concentrations determined by the radioreceptor assay correlated well with levels measured by the ristocetin-induced platelet aggregation method, thus demonstrating the functional relevancy of the radioreceptor assay for plasma FVIII/vWF.     

Follow-Up of Nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography

PurposeThe purpose of this study was to describe capillary changes in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography-angiography (OCT-A) and correlate the results with best corrected visual acuity (BCVA), visual field, OCT retinal nerve fiber layer (RNFL), and combined thickness of ganglion cell and inner plexiform layers (GCIPL) thicknesses.MethodsWe enrolled 22 eyes with acute NAION and 30 normal control (NC) subjects in this study. Whole en face image vessel density (WiVD) was measured in the radial peripapillary capillary plexus (RPC), superficial capillary plexus (SCP), and deep vascular complex (DVC) using OCT-A. The examination was repeated at 1 (M1), 3 (M3), 6 (M6), and 9 (M9) months after presentation for NAION.ResultsThe initial RPC WiVD was significantly reduced in the acute NAION group compared to the NC group (P < 0.0001). Over the course of NAION follow-up, RPC WiVD was significantly reduced at M1 (P < 0.001 compared to M0) and M3 (P < 0.0001 compared to M1). However, there was no significant further decrease at M6 and M9. The initial SCP WiVD was significantly reduced in the NAION group compared to the NC group (P < 0.0001 for both). Over the course of NAION follow-up, a significant decrease was observed for SCP WiVD at M1 (P < 0.001 compared to M0), but no significant change was seen at M3, M6, or M9. DVC was normal in the NAION group. Correlations were found between GCIPL and SCP WiVD in the NAION acute phase (R = 0.604, P = 0.003) and in the M9 atrophic stage (R = 0.551, P = 0.009). At M9, RPC WiVD was correlated with BCVA (R = −0.562, P = 0.007), mean deviation (R = 0.518, P = 0.01), and RNFL (R = 0.655, P = 0.001).ConclusionsOver the course of NAION, OCT-A provided detailed visualization of retinal capillary plexus involvement.     

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome

Background

Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods

We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3–6) after the onset of MMF treatment. The characteristics of responder patients (n?=?74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n?=?22) were compared by univariate analysis and multivariate logistic regression.

Results

Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8–30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p?=?0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p?=?0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p?=?0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR?=?0.80, 95 % CI [0.69, 0.93], p?<?0.01).

Conclusions

MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.

     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

OSAS and upper pharynx surgery: Does basilingual collapsus always rhyme with failure?

ObjectiveDrug-induced-sedation endoscopy (DISE) has proved superior to awake clinical examination for diagnosis of upper-airway obstruction sites and surgical planning. Our question is: does multilevel obstruction on DISE systematically entail failure for surgery limited to the upper pharynx?Material & methodsWe conducted a retrospective single-center study in patients with obstructive sleep apnea syndrome (OSAS) treated by single-level surgery of the upper pharynx (tonsillectomy with or without pharyngoplasty). Preoperative assessment included polysomnography (PSG) and DISE. Surgical efficacy was assessed on postoperative PSG. Treatment response was defined by postoperative apnea-hypopnea index (AHI) < 20 events/h with 50% reduction, and cure by AHI < 10 (patients with preoperative AHI ≤ 10 being excluded). Efficacy was compared between groups without (group A) and with basilingual or laryngeal collapsus on DISE (group B).ResultsWe analyzed 63 patients, with mean preoperative AHI 33.8 ± 17.9 events/h. The two groups (A, n = 36; B, n = 27) were clinically comparable. Postoperative PSG took place at a mean 8.5 ± 11.5 months. The success rate was 66.7% in group A (mean reduction in AHI, 57.3 ± 36.2%) and 59.3% in group B (mean reduction, 53.9 ± 39.2%). Cure rates were respectively 48.5% and 48.1%. There was no statistically significant difference between the two groups (P > 0.1).ConclusionsOropharyngeal surgery can alleviate associated obstructive sites found on DISE in the lower pharynx, and step-by-step treatment shows efficacy equal to that of single-step multilevel surgery.     

C3 nephritic factor associated with C3 glomerulopathy in children

Background

C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF.

Methods

We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes.

Results

Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases.

Conclusions

C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.     

蜂胶对成纤维细胞、单核巨噬细胞系基质金属蛋白酶MMP-9表达的抑制作用

目的探讨蜂胶对糖尿病伤口愈合的作用及其机制。方法采用荧光电泳法,检测不同葡萄糖浓度（5、25mmol／L）和不同蜂胶浓度（10、50、100、200μg／ml）处理的体外培养的人成纤维细胞及单核巨噬细胞系的基质金属蛋白酶MMP-9蛋白的表达。结果高浓度葡萄糖（25mmol／L）状态下,MMP-9表达增加,但与低浓度（5mmol／L）比较,差异无统计学意义。蜂胶可显著降低MMP-9的表达,并呈剂量依赖性（P〈．05）。结论高糖能增加单核巨噬细胞系及成纤维细胞MMP-9的表达,可能会影响糖尿病患者伤口的愈合。蜂胶可抑制这些细胞MMP-9的表达,有益于细胞基质的积聚,从而有益于糖尿病患者伤口的愈合。     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.