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Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.

The antiinflammatory small molecule ibudilast was tested in a phase 2 trial in patients with progressive multiple sclerosis. The rate of brain atrophy over 96 weeks was lower with ibudilast than with placebo. Side effects with ibudilast included GI symptoms and depression.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small blood vessels caused by mutations in the Notch3 gene. Tournier-Lasserve and Bouser describe and autosomal dominant syndrome characterized mainly by recurrent strokes and neuroimaging evidence of leukoencephalopathy, studying 45 members of a single family clinically and with magnetic resonance imaging (MRI; )[1] they were then the first to report the pathologic findings in one of the affected subjects, noting myelin loss and pallor sparing the U-fibers.

Presentation of Case A 75-year-old man was admitted to the hospital because of an impaired mental status, myoclonic jerks, and a tonic—clonic seizure. The patient was right-handed. There was a history of adult-onset diabetes mellitus that was managed with tolbutamide, peripheral neuropathy, and hypertension that was treated with diltiazem. He had discontinued smoking 30 years earlier and did not imbibe alcohol. Five years before admission the patient complained of smelling gas in his home, but representatives of the local gas company found no evidence of a leak. A computed tomographic (CT) cranial scan, performed at this hospital, showed a contrast-enhancing . . .

A complete blood count, routine blood chemical evaluations, the results of a serologic test for syphilis, tests of liver and thyroid function, and a test for antinuclear antibodies, a vitamin B12 level, an electrocardiogram, an x-ray film of the chest, and a toxicity screen were reported to be normal. Another CT scan of the cranium showed no change in the right tentorial meningioma in comparison with the study performed five years earlier; there was marked progression in the low-absorptive, non--contrast-enhancing abnormalities, which involved the right frontal, temporal, parietal, and occipital regions, with less marked findings on the left side; a mass effect created a subfalcial shift toward the left side; the posterior limb of the internal capsule, the external capsule, and the corpus callosum on the right side were involved, as were the left corpus callosum, forceps major, and forceps minor; an area of contrast enhancement, 0.5 cm, was observed in the right temporal subcortical region and was of slightly high-absorptive appearance on the plain scan; cavitary changes were present in the head and adjacent body of the caudate nucleus, abnormalities that were not detected on review of the CT scan performed five years earlier; the cortical sulci were effaced bilaterally.

DCM was classified as probably carcinogenic to humans (Group 2A) on the basis of limited evidence that it causes biliary-tract cancer and non-Hodgkin lymphoma in humans and sufficient evidence of carcinogenicity in experimental animals (malignant lung and hepatocellular tumours in male and female mice).2,3,6-9 In making its overall assessment, the working group also took into account the strong evidence that DCM metabolism via glutathione-S-transferase T1 (GSTT1) leads to the formation of reactive metabolites, that GSTT1 activity is strongly associated with genotoxicity of DCM in vitro and in vivo, and that GSTT1-mediated metabolism of DCM does occur in humans. DNA reactivity was evident in various genotoxicity assays, including in animals and in human cells in vitro. Because 1,3-PS does not require metabolic activation and reacts directly with DNA and other macromolecules, the working group concluded that this mechanism probably operates both in animals and humans.

This cross-sectional study assessed the relationship between the degree of optic nerve pallor (optic atrophy) and visual function. Using a set of \"gold standard\" stereoscopic slides, the severity of optic atrophy for 270 eyes, each having sustained a bout of optic neuropathy, was graded. Good visual acuity was found in 55/86 (64.0%) mild, 54/119 (45.4%) moderate, and 21/65 (32.3%) marked optic atrophy eyes. Good visual field was found in 6/28 (21.4%) mild, 4/43 (9.3%) moderate, and 2/28 (7.1%) marked optic atrophy eyes. Good color vision was found in 31/46 (67.4%) mild, 12/62 (19.4%) moderate, and 7/31 (22.6%) marked optic atrophy eyes. A significant rank correlation was observed between optic atrophy and visual acuity (P < 0.001; rs = 0.356), visual field (P < 0.001; rs = -0.398), and color vision (P < 0.001; rs = -0.492). As the graded severity of optic atrophy increases, the proportion of eyes with good visual function decreases. Visual field, rather than visual acuity or color vision, appears to be a better indicator of the severity of visual loss, when optic atrophy is present.

To the Editor: Whitcomb (Aug. 17 issue) 1 proposes correcting the oversupply of specialists by limiting residencies for graduates of foreign medical schools. The health system in the United States exists not to ensure employment for physicians but to provide medical care. It follows that residency programs should accept the best applicants for available positions in order to supply the public with the best physicians possible. To select the best applicants, all qualified graduates should be permitted to apply. If the result is the displacement of graduates of U.S. medical schools from residency positions, the correct response would be to train . . .

Sickle Cell Disease (SCD) is a serious recessive genetic disorder caused by a single nucleotide polymorphism (SNP) in the -globin gene (HBB). Sickle hemoglobin polymerizes within red blood cells (RBCs), causing them to adopt an elongated \"sickle\" shape. Sickle RBCs damage vasculature, leading to severe symptoms, ultimately diminishing patient quality of life and reducing lifespan. Here, we use co-delivery of a pre-formed Cas9 ribonucleoprotein complex (RNP) and a single-stranded DNA (ssDNA) oligonucleotide donor to drive sequence replacement at the SCD SNP in human CD34+ hematopoietic stem/progenitor cells (HSPCs). Corrected HSPCs from SCD patients produce less sickle hemoglobin protein and correspondingly increased wild-type hemoglobin when differentiated into erythroblasts. When injected into immunocompromised mice, treated HSPCs maintain editing long-term at therapeutically relevant levels. These results demonstrate that the Cas9 RNP/ssDNA donor approach can mediate efficient HSPC gene editing and could form the basis for treatment of SCD by autologous hematopoietic cell transplantation.