Partial rescue of the full-field electroretinogram in patients with RPE65-related retinal dystrophy following gene augmentation therapy with voretigene neparvovec-rzyl.

PURPOSE: To present a series of patients with RPE65-related retinal dystrophy showing a partial rescue of the full-field electroretinogram (ERG) following gene replacement therapy with voretigene neparovec-rzyl (Luxturna®). METHODS: This retrospective chart review examined 17 patients treated with voretigene neparovec-rzyl (VN) at the Casey Eye Institute (2018-2022). The last pre-operative ERG and all available post-operative ERGs were analyzed to identify subjects with functional rescue. Measurements of amplitudes and implicit times were compared to data from age-matched controls and the attenuation relative to the lower limit of normal (LLN) was calculated. For comparison with other functional exams, the last pre-operative and all post-treatment best-corrected visual acuity (BCVA) data, visual field (VF) tests and full-field threshold stimulus tests (FST) were also described. RESULTS: Of patients who underwent ERGs, most had unrecordable ERGs that did not change after treatment. However, we identified three patients, treated bilaterally, who demonstrated partial rescue of the full-field ERG in both eyes which was sustained during the course of the study. CONCLUSIONS: This is the largest series of patients treated with VN showing a partial rescue of the ERG. This is also the first report of bilateral ERG rescue, as well as the first description of ERG recovery occurring in non-pediatric subjects. Full-field ERG could be used in combination with other psychophysical tests and imaging modalities to detect and deepen our understanding of the response to this gene therapy approach.

Deciphering strontium sulfate precipitation via Ostwald's rule of stages: From prenucleation clusters to solution-mediated phase tranformation.

Multiple-step nucleation pathways have been observed during mineral formation in both inorganic and biomineral systems. These pathways can involve precursor aqueous species, amorphous intermediates, or metastable phases. Despite the widespread occurrence of these processes, elucidating the precise nucleation steps and the transformation mechanisms between each step remains a challenging task. Using a suite of potentiometric, microscopic, and spectroscopic tools, we studied the nucleation pathway of SrSO4 as a function of the physico-chemical solution parameters. Our observations reveal that below a threshold supersaturation, nucleation is driven by bound species, akin to the prenucleation cluster model, which directly leads to the formation of the stable phase celestine, SrSO4. At higher supersaturations, this situation is altered, with nucleation dominated by the consumption of free ions. Importantly, this change in nucleation mechanism is coupled to the formation of a hemihydrate metastable phase, SrSO4 · 1/2H2O, which eventually transforms into celestine, adhering to Ostwald's rule of stages. This transformation is a solution-mediated process, also occurring in the presence of a fluid film and is controlled by the physico-chemical parameters of the surrounding environment. It proceeds through the dissolution of the metastable phase and the de novo crystallization of the final phase. Overall, our results reveal that ion association taking place during the prenucleation stage dictates whether the nucleation pathway goes through an intermediate phase or not. This also underlines that although Ostwald's rule of stages is a common process, it is not a prerequisite for mineral formation-even in systems where it can occur.

Multistep nucleation compatible with a single energy barrier: catching the non-classical culprit.

In this work we link experimental results of SrSO4 precipitation with a nucleation model based on mesoscopic nucleation theory (MeNT) to stride towards a cohesive view of the nucleation process that integrates both classical and non-classical views. When SrCl2 and Na2SO4 are co-titrated at slow dosing rates, time-resolved turbidity, conductivity and ion-specific data reveal that the initial stage of the nucleation process is driven by neutral species, i.e. ion-pairs or larger, akin to the prenucleation cluster model. However, when co-titrations are conducted at higher rates, the onset of nucleation is dominated by the consumption of free ions, akin to the explanation provided by classical nucleation theory (CNT). The occurrence of both mechanisms for the same system is explained by a toy model that includes both the thermodynamics (consisting of a single energy barrier) and kinetics of cluster formation formally obtained from MeNT. This gives rise to an effective energy barrier exhibiting a local intermediate minimum, which does not originate from a minimum in the thermodynamic free energy. Rather, it is associated with an increased probability of observing a specific class (in terms of size/density) of precursor clusters due to their slower kinetics. At high supersaturations this minimum in the kinetics of cluster formation becomes less pronounced and the effective barrier is also significantly lowered. Consequently, the probability of observing an intermediate state is blurred and we recover a nucleation pathway more closely following the one envisaged by the classical model. Thus, our model is capable of capturing both single and multistep nucleation mechanisms observed experimentally considering only a single energy barrier.

An evaluation of the species and subspecies of the genus Salmonella with whole genome sequence data: Proposal of type strains and epithets for novel S. enterica subspecies VII, VIII, IX, X and XI.

Species and subspecies within the Salmonella genus have been defined for public health purposes by biochemical properties; however, reference laboratories have increasingly adopted sequence-based, and especially whole genome sequence (WGS), methods for surveillance and routine identification. This leads to potential disparities in subspecies definitions, routine typing, and the ability to detect novel subspecies. A large-scale analysis of WGS data from the routine sequencing of clinical isolates was employed to define and characterise Salmonella subspecies population structure, demonstrating that the Salmonella species and subspecies were genetically distinct, including those previously identified through phylogenetic approaches, namely: S. enterica subspecies londinensis (VII), subspecies brasiliensis (VIII), subspecies hibernicus (IX) and subspecies essexiensis (X). The analysis also identified an additional novel subspecies, reptilium (XI). Further, these analyses indicated that S. enterica subspecies arizonae (IIIa) isolates were divergent from the other S. enterica subspecies, which clustered together and, on the basis of ANI analysis, subspecies IIIa was sufficiently distinct to be classified as a separate species, S. arizonae. Multiple phylogenetic and statistical approaches generated congruent results, suggesting that the proposed species and subspecies structure was sufficiently biologically robust for routine application. Biochemical analyses demonstrated that not all subspecies were distinguishable by these means and that biochemical approaches did not capture the genomic diversity of the genus. We recommend the adoption of standardised genomic definitions of species and subspecies and a genome sequence-based approach to routine typing for the identification and definition of novel subspecies.

Validation of a new in vitro Sun Protection Factor method to include a wide range of sunscreen product emulsion types.

In 2017, Cosmetics Europe performed a double-blinded ring test of 24 emulsion-type sunscreen products, across 3 in vivo test laboratories and 3 in vitro test laboratories, using a new candidate in vitro SPF test method. Based on the results of this work, an article was published showing how data derived from a new lead candidate method conform to new International Standards (ISO) acceptance criteria for alternative SPF test methods (Any alternative method should consider the matrix effect and if required, specify the matrix applicability of the method; Criterion 1a: Systematic differences between methods should be negligible: 95% of all individual results of an alternative method are within the range of ±2× reproducibility standard deviation of the in vivo method, that is overall bias must be below 0.5× reproducibility standard deviation of the in vivo method; Criterion 1b: Measurement uncertainty of an alternative method should be below the measurement uncertainty of the in vivo method. Candidate method predicted values must fall within the full 'funnel' (SPF 6-50+) limits proposed by Cosmetics Europe (derived from the same minimum test design, that is using the ISO24444 Method to measure at least 24 products across at least 3 laboratories using at least 5 test subjects/laboratory, in a blinded fashion).). Of the 24 sunscreen products tested, the majority of emulsions were of the oil-in-water (O/W) type, whereas only one was water-in-oil (W/O) and there were no products with a mineral-only sun filter system. In order to confirm the scope of this method, therefore, a new study was conducted that included 73 W/O (12 mineral + organic, 44 mineral only and 17 organic only) and 3 O/W mineral-only, emulsion-type sunscreen products (a total of 76 new sunscreen products). When combined with the previous 24 products (tested in 3 different laboratories), this yielded a new data set comprising a total of 100 emulsion-type sunscreen products, with SPF values ranging from 6 to 50+ (with a total of 148 data points). These products were tested using the double-plate in vitro SPF test method and compared with the ISO TC217/WG7 acceptance criteria for alternative SPF test methods. Over 95% of paired in vitro: in vivo SPF values lay within the upper and lower limits of the ISO acceptance criteria funnel, with no bias. This new in vitro SPF test method, therefore, meets the minimum requirements for an alternative SPF test method to ISO24444:2010, for emulsion-type sunscreen products (which make up the majority of marketed sunscreen products).

En 2017, Cosmetics Europe a réalisé un ring test en double aveugle de 24 produits de protection solaire de type émulsion, dans 3 laboratoires de test in vivo et 3 laboratoires de test in vitro, en utilisant une nouvelle méthode de test SPF in vitro. Sur la base des résultats de ces travaux, un article a été publié montrant comment les données dérivées de cette nouvelle méthode sont conformes aux nouveaux critères d'acceptation des normes internationales (ISO) pour les méthodes de test SPF alternatives. Sur les 24 produits de protection solaire testés, la majorité des émulsions étaient du type huile dans l'eau (H / E), tandis qu'un seul était de l'eau dans l'huile (E / H) et il n'y avait aucun produit contenant uniquement des minéraux. Afin de confirmer cette méthode, une nouvelle étude a donc été menée comprenant 73 produits E/ H (12 produits contenant des filtres minéraux + organiques, 44 produits contenant des filtres minéraux uniquement et 17 produits contenant des filtres organiques uniquement) et 3 produits H / E contenant des filtres minéraux uniquement, tous de type émulsion (donc un un total de 76 nouveaux produits de protection solaire). Combiné aux 24 produits précédents (testés dans 3 laboratoires différents), cela a donné un nouvel ensemble de données comprenant un total de 100 produits de protection solaire de type émulsion, avec des valeurs SPF allant de 6 à 50+ (avec un total de 148 points de données) . Ces produits ont été testés à l'aide de la méthode de test SPF in vitro double approche et comparés aux critères d'acceptation de l'ISO TC217 / WG7 pour les méthodes alternatives du SPF in vivo. Plus de 95% des valeurs de SPF appariées in vitro: in vivo se situent dans les limites supérieure et inférieure de l'entonnoir des critères d'acceptation ISO, sans biais. Cette nouvelle méthode de test SPF in vitro, par conséquent, répond aux exigences minimales d'une méthode de test SPF alternative à ISO24444: 2010, pour les produits de protection solaire de type émulsion (qui constituent la majorité des produits de protection solaire commercialisés).

SeqSero2: Rapid and Improved Salmonella Serotype Determination Using Whole-Genome Sequencing Data.

SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/SeqSero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification.IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing.

Probing the Single-Particle Character of Rotational States in

A beam containing a substantial component of both the J^{π}=5^{+}, T_{1/2}=162 ns isomeric state of ^{18}F and its 1^{+}, 109.77-min ground state is utilized to study members of the ground-state rotational band in ^{19}F through the neutron transfer reaction (d,p) in inverse kinematics. The resulting spectroscopic strengths confirm the single-particle nature of the 13/2^{+} band-terminating state. The agreement between shell-model calculations using an interaction constructed within the sd shell, and our experimental results reinforces the idea of a single-particle-collective duality in the descriptions of the structure of atomic nuclei.

Validation of an in vitro sun protection factor (SPF) method in blinded ring-testing.

OBJECTIVE: The objective of this work was to investigate the utility of a new in vitro SPF test method in blinded ring-testing, against new ISO acceptance criteria. METHODS: Twenty four blinded, commercial, emulsion-type, primary sunscreen products, covering the full range of labelled SPF in Europe (SPF6 - 50+), were tested by three test institutes using the current ISO24444:2010 In Vivo SPF Test Method and simultaneously by three separate test laboratories using a new candidate in vitro SPF test method, developed under the leadership of Cosmetics Europe (CE). The resulting relationship between in vitro SPF and in vivo SPF values was then compared with acceptance criteria developed recently by the International Standards (ISO) TC217/WG7 Sun Protection Test Methods Working Group. RESULTS: Analysis of the mean inter-laboratory in vitro and mean inter-institute in vivo SPF values revealed a strong correlation between in vitro and in vivo values, with a Pearson correlation coefficient of r2  = 0.88 (P < 0.0001), a slope of 1.01 and a non-significant intercept (-1.48; P = 0.62). When these data were compared to the new ISO WG7 acceptance criteria, method bias was found to be extremely low and over 95% of the coupled data lay within the model 'funnel' (defined by upper and lower confidence intervals). CONCLUSION: In conclusion, the results of blinded ring testing and comparison to new ISO WG7 acceptance criteria indicate that a new in vitro SPF test method meets (and exceeds) these minimum criteria and is an interesting candidate for possible deployment as an industry test methodology.

[Traumatic hip dislocation in a 6-year-old male child: Seldom but demanding]. / Die Traumatische Hüftgelenkluxation eines 6­jährigen Jungen: Selten, aber anspruchsvoll.

Traumatic hip dislocations in children are not frequent but constitute true emergencies. They require urgent reduction because of the risk of consecutive avascular necrosis of the femoral head. We report a 6-year-old boy with traumatic posterior hip dislocation on a vacation abroad. After closed reduction the day of the accident, a hip spica cast was applied and the patient was transferred home. Once home, X­ray and CT diagnostics were completed by MRI. In future, long-term clinical and radiological investigations for avascular necrosis and growth disorders, as well as thoroughly informing the parents, should be mandatory.

Statin intake is associated with MMP-1 level in gingival crevicular fluid of patients with periodontitis.

BACKGROUND: This study was conducted to assess whether statin intake is associated with clinical parameters of periodontitis and matrix metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) of non-diabetic and diabetic patients. METHODS: We first determined the effect of simvastatin on MMP expression in mononuclear cells. We then recruited 117 non-diabetic and diabetic patients, who all had periodontitis and took or did not take statin, and measured periodontal probing depth (PPD) and clinical attachment level (CAL), and collected gingival crevicular fluid (GCF) to quantify MMPs. RESULTS: The in vitro studies showed that simvastatin potently inhibited the expression of MMP-1, MMP-8, and MMP-9 upregulated by lipopolysaccharide (LPS) and high glucose in mononuclear cells. The patient study showed that, after adjusting for age and smoking status, PPD in diabetic patients on statin was significantly less than that in diabetic patients not on statin. MMP-1 level in GCF of non-diabetic and diabetic patients on statin was lower than that of non-diabetic and diabetic patients not on statin, respectively. No difference was found for MMP-8 and -9 levels in GCF. CONCLUSION: Statin intake is associated with reduced PPD in diabetic patients and MMP-1 level in GCF in either non-diabetic or diabetic patients.

Use of Whole Genome Sequencing by the Federal Interagency Collaboration for Genomics for Food and Feed Safety in the United States.

ABSTRACT: This multiagency report developed by the Interagency Collaboration for Genomics for Food and Feed Safety provides an overview of the use of and transition to whole genome sequencing (WGS) technology for detection and characterization of pathogens transmitted commonly by food and for identification of their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among the following federal agencies: National Institutes of Health; Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA); and the U.S. Department of Agriculture, Food Safety and Inspection Service, Agricultural Research Service, and Animal and Plant Health Inspection Service. We describe single nucleotide polymorphism, core-genome, and whole genome multilocus sequence typing data analysis methods as used in the PulseNet (CDC) and GenomeTrakr (FDA) networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Interagency Collaboration partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles) and source attribution efforts and increase transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information. We also highlight the impact of current trends in the use of culture-independent diagnostic tests for human diagnostic testing on analytical approaches related to food safety and what is next for the use of WGS in the area of food safety.

[Repeated prevalence investigations of nursing home-associated infections as a tool to assess the hygienic quality of care]. / Wiederholte Prävalenzuntersuchungen Pflegeheim-assoziierter Infektionen als Instrument zur Erfassung der hygienischen Ergebnisqualität.

The rate of healthcare-associated infections can be regarded as an important outcome parameter of the hygienic quality of care in nursing homes. Our study aimed to evaluate the applicability of repeated prevalence investigations as a tool for surveillance of healthcare-associated infections in nursing homes. From December 2006 to September 2007 a total of five prevalence investigations were conducted in four nursing homes each (n=2,369 residents). Initially, defined structural and procedural parameters of the hygienic quality of the four nursing homes were evaluated based on a detailed inspection and a checklist including 40 parameters. The results showed a uniformly high level of the hygienic quality with only minor variation (mean 84%, range 75%-93% of parameters fulfilled). In total, the prevalence of healthcare-associated infections was 6.8%, with a marked increase with higher categories of dependency (3.5%, 4.0%, 8.5%, and 12.3%, respectively, in the categories 0, I, II, and III of the German grading of skilled nursing care). Respiratory tract (4.1%), skin/soft tissue (1.5%), and urinary tract infections were the most prevalent healthcare-associated infections. Respiratory tract infections showed a marked seasonal pattern. During the second prevalence investigation (February 2007), an outbreak of upper respiratory tract infections occurred in one of the nursing homes (attack rate, 17%). The crude prevalence rates showed considerable differences between the four nursing homes; however, after adjusting for the different categories of dependency, the standardized infection rates (SIR) were largely comparable (excluding the outbreak). After inclusion of the outbreak, the SIR of the specific nursing home was significantly higher compared to all other nursing homes. In conclusion, our study shows that repeated prevalence investigations can be an easy to use tool for surveillance of healthcare-associated infections as a surrogate parameter of the hygienic quality in nursing homes. This implies a knowledge of the seasonality of specific infections and a risk adjustment according to the categories of dependency. The primary intention of surveillance should be the identification of hygienic problems. However, the resources should preferentially be focused on hygienic structures and processes.

Extent of Microstructural Tissue Damage Correlates with Hemodynamic Failure in High-Grade Carotid Occlusive Disease: An MRI Study Using Quantitative T2 and DSC Perfusion.

BACKGROUND AND PURPOSE: Chronic hemodynamic impairment in high-grade carotid occlusive disease is thought to cause microstructural abnormalities that might be subclinical or lead to subtle symptoms including cognitive impairment. Quantitative MR imaging allows assessing pathologic structural changes beyond macroscopically visible tissue damage. In this study, high-resolution quantitative T2 mapping combined with DSC-based PWI was used to investigate quantitative T2 changes as a potential marker of microstructural damage in relation to hemodynamic impairment in patients with unilateral high-grade carotid occlusive disease. MATERIALS AND METHODS: Eighteen patients with unilateral high-grade ICA or MCA stenosis/occlusion were included in the study. T2 values and deconvolved perfusion parameters, including relative CBF, relative CBV, and the relative CBF/relative CBV ratio as a potential indicator of local cerebral perfusion pressure, were determined within areas with delayed TTP and compared with values from contralateral unaffected areas after segmentation of normal-appearing hypoperfused WM and cortical regions. Hemispheric asymmetry indices were calculated for all parameters. RESULTS: Quantitative T2 was significantly prolonged (P < .01) in hypoperfused tissue and correlated significantly (P < .01) with TTP delay and relative CBF/relative CBV reduction in WM. Significant correlations (P < .001) between TTP delay and the relative CBF/relative CBV ratio were found both in WM and in cortical areas. CONCLUSIONS: Quantitative T2 can be used as a marker of microstructural tissue damage even in normal-appearing GM and WM within a vascular territory affected by high-grade carotid occlusive disease. Furthermore, the extent of damage correlates with the degree of hemodynamic failure measured by DSC perfusion parameters.

Efficacy of Mechanical Thrombectomy Using Stent Retriever and Balloon-Guiding Catheter.

PURPOSE: Intra-arterial therapy of acute ischemic stroke has developed rapidly in recent years. Due to proven efficacy in randomized trials, stent retrievers were replacing first-generation thrombectomy devices and have been defined as method of choice. However, aspiration catheters or a combination of several techniques have shown promising rates of successful recanalizations. To create a basis for comparison of the new approaches according to real-world data, we determined the first pass recanalization rate of an evidence-based standard technique with the use of a stent retriever in combination with a balloon-guiding catheter. The assessment was based on the number of required passages and reperfusion rate, but not on clinical results. METHODS: Patients from our institution with anterior circulation occlusions and mechanical thrombectomy by using stent retrievers in combination with balloon-guiding catheters were analyzed retrospectively. Reperfusion was graded with the "thrombolysis in cerebral infarction" (TICI) classification on post-interventional angiograms. Additionally, the number of passes and the duration of the recanalization procedure were recorded. RESULTS: Between 2014 and July 2017, 201 patients met the inclusion criteria. Successful recanalization, defined as a TICI scale 2b/3, was 91% (TICI 2b was achieved in 44% and TICI 3 in 47%) after the procedure. After the first passage, successful recanalization was achieved in 65% of the patients. Mean number of passes was 1.4 (1-5 passes) for all patients. Median duration of the procedure was 49 min (0:11-2:35 h). CONCLUSIONS: Even a standard thrombectomy technique with the use of a stent retriever together with a balloon-guiding catheter provides reasonable recanalization rates with only one passage. The results can be taken as benchmark for alternative and more complex techniques.

Three-dimensional imaging of carbonyl sulfide and ethyl iodide photodissociation using the pixel imaging mass spectrometry camera.

The Pixel Imaging Mass Spectrometry (PImMS) camera is used in proof-of-principle three-dimensional imaging experiments on the photodissociation of carbonyl sulfide and ethyl iodide at wavelengths around 230 nm and 245 nm, respectively. Coupling the PImMS camera with DC-sliced velocity-map imaging allows the complete three-dimensional Newton sphere of photofragment ions to be recorded on each laser pump-probe cycle with a timing precision of 12.5 ns, yielding velocity resolutions along the time-of-flight axis of around 6%-9% in the applications presented.

Short-term protein loading in assessment of patients with renal disease.

The effect of short-term protein loading on the glomerular filtration rate in normal persons and patients with renal disease was evaluated. Previous studies have demonstrated that in healthy subjects, protein loading results in an increased glomerular filtration rate. By determining the glomerular filtration rate preceding (baseline glomerular filtration rate) and following (test glomerular filtration rate) oral protein loading, it was possible to define (1) the filtration capacity (test glomerular filtration rate) and (2) the renal reserve (test glomerular filtration rate - baseline glomerular filtration rate) of the kidney. In normal persons, filtration capacity averaged 157 +/- 13 ml per minute and renal reserve 34 ml per minute. The test glomerular filtration rate was reproducible and independent of protein intake, whereas baseline glomerular filtration rate was significantly influenced by diet. Patients with renal disease were found to have a reduced renal reserve and/or a diminished filtration capacity. The reduction in filtration capacity appears to correlate with the damage sustained by the organ. It is suggested that an abnormal response to protein loading in renal disease may herald the fall in the baseline glomerular filtration rate and the rise in plasma creatinine level.

Renal hemodynamic changes in humans. Response to protein loading in normal and diseased kidneys.

This study was undertaken to define the renal hemodynamic changes that mediate the acute response to an oral protein load. Three groups of subjects were studied: (1) disease-free subjects; (2) patients with chronic renal disease of various causes, except for diabetes mellitus, documented by history and/or renal biopsy; and (3) patients with diabetes mellitus, that is, a history of hyperglycemia requiring antihyperglycemic therapy. All subjects were studied before (baseline) and after (test) ingestion of a protein load. Glomerular filtration rate and effective renal plasma flow were evaluated by inulin and para-amino-hippurate, respectively. In the disease-free subjects, the mean baseline glomerular filtration rate and renal plasma flow were 122 +/- 10 ml/minute/1.73 m2 and 644 +/- 64 ml/minute/1.73 m2, whereas test glomerular filtration rate and renal plasma flow were 151 +/- 15 ml/minute/1.73 m2 and 791 +/- 111 ml/minute/1.73 m2, respectively. In patients with chronic renal disease, the test glomerular filtration rate and renal plasma flow were related to the severity of the disease. The more severe the disease, the lower the absolute test values and the smaller the increment from baseline to test values. Patients with diabetes mellitus had a paradoxic response to ingestion of a protein load. Glomerular filtration rate fell while renal plasma flow remained unchanged. This response was observed in all diabetic patients regardless of the type of diabetes or whether clinical evidence of diabetic nephropathy was absent, minimal, or severe.

Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate.

This study was designed to investigate the effect of protein intake on glomerular filtration rate, and to demonstrate and evaluate the functional reserve of the kidney. Normal subjects ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. A progressive increment in protein intake in normal volunteers resulted in a significant increase in creatinine clearance. Diurnal variations in creatinine clearance were found. These daily variations correlated well with the periods of food intake. The capacity of the kidney to increase its level of function with protein intake suggests a renal function reserve. In short-term studies, the effect of a protein load on glomerular filtration rate was evaluated. Normal subjects showed an increase in glomerular filtration rate two and a half hours after protein load to a maximal glomerular filtration rate of 171.0 +/- 7.7 ml per minute. In patients with a reduced number of nephrons, renal functional reserve may be diminished or absent.

Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma.

PURPOSE: To determine whether chronic topical glaucoma therapy can control intraocular pressure (IOP) and protect nerve fibers in a rat model of pressure-induced optic nerve damage. METHODS: Sixteen adult Brown Norway rats were-administered unilateral episcleral vein injections of hypertonic saline to produce scarring of the aqueous humor outflow pathways. Twice daily applications of either artificial tears (n = 6), 0.5% betaxolol (n = 5), or 0.5% apraclonidine (n = 5) were delivered to both eyes, and awake pressures were monitored with a TonoPen XL tonometer for 17 days before the rats were killed. RESULTS: For animals administered artificial tears, the mean IOP of the experimental eyes was 39 +/- 2 mm Hg compared with 29 +/- 1 mm Hg for the control eyes. This difference was statistically significant (P < 0.001). Mean IOPs in the experimental eyes of animals administered betaxolol and apraclonidine were 29 +/- 7 and 29 +/- 4 mm Hg, respectively, whereas the mean IOP in the control eyes was 28 +/- 1 mm Hg for both groups. There was no statistically significant difference among these values. The mean IOP for the experimental eyes in the betaxolol and apraclonidine groups was lower than that in animals administered artificial tears (P = 0.003). Quantitative histologic analysis of optic nerve damage in experimental eyes showed that four of the six animals administered artificial tears had damage involving 100% of the neural area. This degree of damage appeared in only 3 of 10 animals administered glaucoma therapy. Optic nerve protection was closely correlated with IOP history because damage was limited to less than 10% of the cross-sectional area in all animals in which the maximal IOP was less than or equal to 39 mm Hg, more than 2 SD below the mean value for eyes administered artificial tears. CONCLUSIONS: Topical glaucoma therapy in this model can prevent IOP elevation and protect optic nerve fibers.