Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration

Magnetic resonance spectroscopy allows neurochemistry to be probed noninvasively in vivo. Recent advances in our understanding of the biochemical significance of the various neurochemicals that are observable allow a variety of pathologic states of relevance to encephalopathies and neurodegenerative disorders to be observed. Measurements of brain glutamate and glutamine allow observation of neuronal/glial substrate cycling and ammonia detoxification. Myo-inositol allows changes in cerebral osmolarity and gliosis to be observed. N-acetylaspartate is a marker of neuronal health and number. Lactate allows nonoxidative glycolysis to be observed. These molecules are now being used to ask etiologic questions that are of relevance to encephalopathies and neurodegeneration, as well to probe longitudinally both natural history and therapeutic interventions in these conditions. Combined with recent advances in anatomic magnetic resonance imaging as well as perfusion magnetic resonance imaging, magnetic resonance spectroscopy has the potential to aid greatly in our understanding of neuronal dysfunction in a wide variety of neurologic pathologies, even in single patients.     

Susceptibility to local infection in biological internal fixation

Resistance to local infection after fracture fixation with plate osteosynthesis may be influenced by the implantation technique. It is known that the extent of the surgical approach to the bone can compromise the local defence capacity. We have investigated susceptibility to infection after a local bacterial challenge in rabbit tibiae using either the open surgical approach for ‘biological’ internal fixation of standard 2.0 dynamic compression plates or the method of minimally invasive plate osteosynthesis (MIPO), a percutaneous, tunnelling insertion technique preserving the integrity of the overlying soft tissue. After the wounds had been closed, various concentrations of Staphylococcus aureus were injected in the direct vicinity of the implants. The infection rate for the open surgical technique was 38.5% and that for the MIPO technique, 25%. This difference is not statistically significant (P > 0.05) suggesting that resistance to local infection associated with the MIPO method is at least equivalent to the open approach for plate osteosynthesis. Received: 22 January 1998     

Differential diagnostic considerations in microcephalic dwarfism

PURPOSE: While the rare Seckel-Syndrome is defined by clear criteria, clinical and radiologic findings for microcephalic osteodysplastic primordial dwarfism (MOPD) make an exact diagnosis and classification difficult. By comparing our patients to previously described cases of MOPD we evaluate the hypothesis that this disorder has a greater heterogeneity than has been believed up until now. Furthermore the differential diagnosis of the MOPD-complex is discussed. RESULTS: Two cases that show typical growth retardation, microcephalus and facial anomalies as well as osteodysplastic deformities including hip dysplasia are presented. The parents of both children are consanguineous and of Arabic race. In one of the children growth hormone levels were noticeably decreased. In discrepancy to the Seckel-syndrome both children showed no signs of mental retardation, therefore the classification into the heterogeneous group of microcephalic osteodysplastic primordial dwarfism (MOPD) is the most likely diagnosis. CONCLUSION: It is suggested that microcephalic osteodysplastic primordial dwarfism (MOPD) has a greater clinical and radiological expression than has been assumed up until now. Whether our results are merely a variant or suggest a new subtype of the MOPD can only be resolved by further cases. The exact pathogenesis of the disease currently remains unknown but the most probable cause is an autosomal recessive inheritance.     

Dietary fructose intolerance: diet modification can impact self-rated health and symptom control.

Carbohydrate intolerance to lactose is widely accepted as a cause of gastrointestinal symptoms, but controversy persists on how important dietary fructose intolerance (DFI) is in causing gastrointestinal pain and suffering and if an elimination diet can control the presenting complaints. The objective of this study was to identify a group of well-defined DFI patients and explore whether dietary education followed by dietary compliance could control symptoms and improve quality of life. During a 5-year period, patients referred to a pancreato-biliary clinic were evaluated for dietary carbohydrate intolerances if they presented with gastrointestinal pain and/or gas and/or bloating and/or diarrhea. Patients were tested with a standardized mixture of glucose, fructose, and lactose diluted in sterile water. End-expiratory breath samples were collected for hydrogen and methane measurement. Symptoms were scored using a 9-point symptom questionnaire. The patients underwent in-depth education by a dietician, and were provided with access to a cookbook, a newsletter, and a support group. A dietary questionnaire was used to evaluate compliance with the fructose-restricted diet. DFI can cause significant gastrointestinal symptoms that may not respond to medications or surgical interventions. Symptoms can improve and self-rated health does improve in DFI patients willing to adhere to a low fructose diet.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343