Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na + )-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH) 2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P,0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH) 2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.
BackgroundElective intraparenchymal intracranial pressure (ICP) monitoring is useful for the diagnosis and treatment of hydrocephalus and cerebrospinal fluid (CSF) disorders. This retrospective study analyzes median ICP and pulse amplitude (PA) recordings in neurosurgically naïve patients undergoing elective ICP monitoring for suspected CSF disorders.MethodsRetrospective review of prospectively collated database of neurosurgically naïve patients undergoing elective ICP monitoring for suspected hydrocephalus and CSF disorders. Following extraction of the median ICP and PA values (separated into all, day and night time recordings), principal component analysis (PCA) was performed to identify the principal factors determining the spread of the data. Exploratory comparisons and correlations of ICP and PA values were explored, including by post hoc diagnostic groupings and age.ResultsA total of 198 patients were identified in six distinct diagnostic groups (n = 21–47 in each).The PCA suggested that there were two main factors accounting for the spread in the data, with 61.4% of the variance determined largely by the PA and 33.0% by the ICP recordings.Exploratory comparisons of PA and ICP between the diagnostic groups showed significant differences between the groups. Specifically, significant differences were observed in PA between a group managed conservatively and the Chiari/syrinx, IIH, and NPH/LOVA groups and in the ICP between the conservatively managed group and high-pressure, IIH, and low-pressure groups. Correlations between ICP and PA revealed some interesting trends in the different diagnostic groups and correlations between ICP, PA, and age revealed a decreasing ICP and increasing PA with age.ConclusionsThis study provides insights into hydrodynamic disturbances in different diagnostic groups of patients with CSF hydrodynamic disorders. It highlights the utility of analyzing both median PA and ICP recordings, stratified into day and night time recordings.
Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left‐ and right‐sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure‐function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub‐types of language representation, both of which will be useful in planning surgery to spare language function.
AS MEDICAL SCIENCE HAS GROWN MORE COMPLEX in the last few decades, we have often found ourselves depending on experimental tools that are beyond our individual abilities to understand. A danger in our use of these tools is that through oversimplification we misinterpret the meaning of the results they give. ST-segment mapping is such a tool. Increasingly, experimental and clinical studies are made that depend on ST-segment changes as a monitor of potentially irreversible ischemic injury to heart muscle. However, there are major conceptual questions as to the independent reliability of ST-segment deviation as a measure of ischemia. It would be dangerous to accept a correlation between ST-segment changes and ischemia under particular experimental conditions in animals as proof that the technique is reliable under clinical circumstances.A large body of electrophysiological knowledge has been gathered over many decades, and it is appropriate to consider if the use of ST-segment measurement for sizing of ischemic regions is consistent with this electrophysiologic theory. We would like to emphasize that this electrophysiologic theory of the origin of the ECG is not a "flight of fancy" by one individual, an improper use of the word theory, but it is the intellectual framework that has developed over decades through the work of hundreds of investigators.This editorial draws from this theory to interpret ST-segment potentials and to identify the sorts of problems that we can expect to encounter with ST mapping. Specifically, we can argue that the ST segments are dependent on the shape and location of the ischemic area within the ventricular wall in relation to location of the electrodes. Under some circumstances ischemia could become more severe or more extensive with no change in ST-segments or with a return toward the isoelectric level. Since the STsegment level is determined by interaction between the normal area and the ischemic area, interventions that alter resting or action potentials in the normal muscle could either accentuate or reduce ST-segment elevation without altering the size or intensity of ischemia. Therefore we conclude that ST-segment mapping should be considered a reliable tool only in a controlled laboratory environment. Its use to guide the physician in patient care is premature and is likely to be misleading.
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