tbuckley/cabot-search huggingface dataset:
SPECT Imaging for Brain Improvement Quantification in a Patient With Cerebrotendinous Xanthomatosis
Authors: Albert Selva-O'Callaghan, Ignasi Bardes, Carlos Jacas, Lluis Jubany, Carles Lorenzo-Bosquet, Gemma Cuberas-Borrós, Miquel Vilardell-Tarres
Journal: Clinical Nuclear Medicine (2010)

Cerebrotendinous xanthomatosis is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene (CYP27), which leads to reduced synthesis of bile acids, particularly chenodeoxycholic acid (Cali et al, J Biol Chem. 1991;266:7779-7783; Gallus et al, Neurol Sci. 2006;27:143-149). The disease is characterized by progressive neurologic dysfunction due to accumulation of cholestanol in neurologic tissues (Moghadasian et al, Arch Neurol. 2002;59:527-529; Selva-O'Callaghan et al, Rheumatology. 2007;46:1212-1213). Long-term treatment with chenodeoxycholic acid can arrest or even reverse progression of the disease (Pierre et al, J Inherit Metab Dis. In press).Brain SPECT with 740 MBq of Tc-99m ethyl cysteinate dimmer, using a double-head gamma camera (Siemens E.cam) with high-resolution, low-energy parallel collimators was performed in our patient at onset and 2 years after starting chenodeoxycholic acid treatment. SPECT acquisitions were performed using a 360-degree orbit, 1 image/30 seg/3 degree, and 128 × 128 matrix. Reconstruction was by means of filtered back-projection, Butterworth 5/0.25, without attenuation correction. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam (Segami Corporation). To visually identify abnormal perfusion regions, volume render brain image was computed, where abnormal perfusion regions were found by comparing with age-matched normal database, and Brodmann areas (BA) were quantified. Pre- versus post-treatment changes were computed by means of relative percentage between counts. Post-treatment SPECT showed better perfusion than pretreatment SPECT with an increase between 5% and 10% in frontal cortex (BA 9, BA 24, BA 32, BA 46, BA 47), parietal cortex (BA 5, BA 31), and temporal cortex (BA 20, BA 22, BA 28, BA 36, BA 37, BA 38), and with an increase of more than 10% in frontal cortex (BA 45) and parietal cortex (BA 23). This case illustrates the benefit of bile acid therapy for halting and even reversing neurologic retardation in this condition.
Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily
Authors: Theodore A. Slotkin, Frederic J. Seidler, Fabio Fumagalli
Journal: Environmental Health Perspectives (2007)

The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury.We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1-4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon.Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem.Chlorpyrifos and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgf22. However, they differed in that the effects on fgf2 and fgfr4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1.The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoxicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcomes.
Mesomelic Dwarfism
Authors: Donald Pinals
Journal: JAMA (1965)

IN 1929 Leri and Weill<sup>1</sup>first described an unusual type of dwarfism that involved mostly the middle segments of the extremities with a characteristic appearance of the forearm. Twelve additional case reports have subsequently appeared in the European literature.<sup>2-5</sup>To our knowledge, no previous cases have been published in the American literature with the exception of a European case incorporated by Rubin into his monograph.<sup>6</sup> <h3>Report of a Case</h3> The patient is a 21-year-old white woman born in the United Kingdom and presently employed in the United States. She was first seen in the emergency room of the New Rochelle Hospital on Jan 15, 1965, after sustaining trauma to her right forearm. An unusual deformity of the right forearm was noted, further roentgenograms were obtained, and the diagnosis of mesomelic dwarfism was established. The patient stated that she never had any difficulty in performing the usual household
Non-invasive imaging in pancreatitis
Authors: P. Rogers, T. Adlan, G. Page
Journal: BMJ (2014)

#### Learning points

##### Early pancreatitis

##### Deteriorating pancreatitis

##### Obstructive pancreatitis

##### Severe pancreatitis

An active 73 year old patient with a history of cholecystectomy, hypothyroidism, and hypertension presented to the emergency department with a five hour history of severe epigastric pain. Her admission blood tests showed an amylase of 782 U/L and a white cell count of 21.2×103/µL, with a neutrophil count of 17.5×103/µL. The patient’s initial modified Glasgow score for predicting the severity of pancreatitis on admission was two, scoring on both age and white cell count. A repeat Glasgow score the following day …
A new specific assay for the detection of DNA immune complexes: its relevance in SLE.
Authors: P Klemp, O L Meyers, E H Harley
Journal: Annals of the Rheumatic Diseases (1983)

Double-stranded DNA immune complexes (DNA-ICs) were assayed by millipore filtration and deoxyribonuclease digestion in 40 patients with both active and inactive systemic lupus erythematosus (SLE). The assay is superior to the double-stranded DNA antibody (ds ADA) as an indicator of active disease, and, when combined with the total haemolytic complement (CH50) and ds ADA levels it increases the prediction of the relative risk of active disease. A good correlation between actual levels of DNA-ICs and the degree of activity was also shown. We conclude that measurement of DNA-ICs is of value as an additional monitor in the assessment of activity in SLE.
The Body in Question
Authors: Samuel Vaisrub
Journal: JAMA (1979)

Based on a British Broadcasting Corporation television series, this imaginative, beautifully illustrated historical overview of important developments in medicine looks like a "coffee-table" book and reads like an adventure story. It is, however, a serious work that carries, among others, two important, albeit controversial, messages. Miller contends that medicine's progress owes less to therapeutic advances than to discoveries of how the body functions and that these insightful discoveries derive from metaphors usually extrapolated from mechanical models. Harvey's discovery of the circulation was evoked by the model of fire pumps, Sherrington's discovery of neural autoregulation by that of automated machines. Whether or not one agrees with Miller, one need not forego the pleasure of reading his book, which, although not intended primarily for physicians, cannot fail to interest and delight them.
A Role for Neutral Sphingomyelinase-mediated Ceramide Production in T Cell Receptor–induced Apoptosis and Mitogen-activated Protein Kinase–mediated Signal Transduction
Authors: Laura Tonnetti, Maria-Concetta Verí, Ezio Bonvini, Luciano D'Adamio
Journal: The Journal of Experimental Medicine (1999)

Studying apoptosis induced by T cell receptor (TCR) cross-linking in the T cell hybridoma, 3DO, we found both neutral sphingomyelinase activation and production of ceramide upon receptor engagement. Pharmacological inhibition of ceramide production by the fungal toxin, fumonisin B1, impaired TCR-induced interleukin (IL)-2 production and programmed cell death. Addition of either exogenous ceramide or bacterial sphingomyelinase reconstituted both responses. Moreover, specific inactivation of neutral sphingomyelinase by antisense RNA inhibited IL-2 production and mitogen-activated protein kinase activation after TCR triggering. These results suggest that ceramide production by activation of neutral sphingomyelinase is an essential component of the TCR signaling machinery.
Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients
Authors: Elani Streja, Wei Ling Lau, Leanne Goldstein, John J. Sim, Miklos Z. Molnar, Allen R. Nissenson, Csaba P. Kovesdy, Kamyar Kalantar-Zadeh
Journal: Kidney International Supplements (2013)
Learning medicine. Interviews and offers.
Authors: P Richards
Journal: BMJ (1983)

Opinion differs widely and deeply on the value and fairness of an interview as part of the process for selecting medical students.Two thirds of medical schools interview the strongest applicants and use the interview to decide among them; the remainder interview only a small number of applicants, such as mature students, in an attempt to assess more fully their motivation and circumstances.Applicants who object to interviews, who doubt their ability to speak up for themselves, or who think that in speaking up they may prejudice their chances of admission can confine their applications to schools which normally do not interview (see table ).Interviewing policies of United Kingdom medical schools.Schools interview either normally (shown by a tick) or only occasionally
Abstract 3314: Potential role of mitochondrial respiration in serum-induced tumor stem cell differentiation
Authors: Naima Hammoudi, Feng Wang, Peng Huang
Journal: Cancer Research (2011)

Abstract Glioblastoma remains the deadliest form of brain tumors. The poor prognosis of glioblastoma patients is associated with a high rate of relapse after therapy. It has been suggested that the presence of cancer stem cells, which are relatively resistant to radiation and chemotherapy, may play a significant role in the recurrence of brain tumor. Understanding the biological property of brain tumor stem cells is important to develop effective therapeutic strategies for glioblastoma. In vitro, glioblastoma stem cells cultured in serum-free medium form self-renewing neurospheres, express the neural stem marker CD133, and are highly tumorigenic. On the other hand, in the presence of fetal bovine serum (FBS), the glioblastoma stem cells tend to undergo differentiation. In this study we used glioblastoma stem cells, NSC11 and NSC23, previously isolated from glioblastoma patients and expressed stem cell markers CD133 and SOX 2, to explore their bioenergetics by monitoring the oxygen consumption as an indication of mitochondrial respiration cultured in serum-free medium in comparison with that incubated in medium containing 5% FBS. We found that NSC11 and NSC23 stem cells exhibited low mitochondrial respiration when cultured in stem cell medium without serum. Upon exposure to 5% fetal bovine serum, mitochondrial respiration increased significantly. Moreover we assessed the protein expression of the mitochondrial respiratory complex (MRC) components in the cells cultured in serum-free medium in comparison with that in medium containing 5% FBS for various lengths of time by western blotting analysis. We observed a marked up-regulation of the protein subunits of MRC complexes I and IV in glioblastoma stem cells when they were exposed to FBS. Analysis of the mRNA expression levels for the mitochondrial DNA-encoded MRC components showed an increase in the expression of these genes, indicating an increase in the mitochondria biogenesis upon the FBS exposure. Based on these preliminary findings, we postulate that maintaining low mitochondrial respiration may be important to maintain the stemness of the glioblastoma stem cells, while the activation of the respiration may promote stem cell differentiation and affect their tumorgenecity. Further studies are required to elucidate the detail molecular pathways governing glioblastoma stem cell self-renewal and differentiation and the mechanistic link to mitochondrial function. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3314. doi:10.1158/1538-7445.AM2011-3314
Alternative pathway complement activation: a possible mechanism inducing skin lesions in benign gonococcal sepsis
Authors: REINER SCHERER, OTTO BRAUN-FALCO
Journal: British Journal of Dermatology (1976)

In order to elucidate the pathogenesis of the skin lesions in 'benign gonococcal sepsis' direct immunofluorescence of an early macular lesion and routine histopathology of a mature papulopustular lesion in a patient with septic gonococcal dermatitis have been performed. Histopathology of the mature skin lesion revelaed a pattenr of 'allergic vasculitis'. Direct immunofluorescence showed exclusively deposits of C3 around and within the capillaries and in the basement membrane zone. No specific IgG, IgM, IgA or C4 deposits could be demonstrated. This, together with serological findings and reports from the literature, suggests an important pathogenetic function for complement, activated through the alternative pathway by means of gonococcal endotoxic lipopolysaccharide, in the pathogenesis of the skin lesions in benign gonococcal sepsis.
Pediatric-Child Psychiatry Collaboration in a Health Maintenance Organization
Authors: NORTON GARBER
Journal: American Journal of Psychiatry (1973)

The author describes a collaborative program between the child psychiatry and pediatric services of a prepaid group practice plan that included weekly meetings between the psychiatrist and the pediatric staff, meetings also involving other disciplines, and clinical evaluations of referred patients. The advantages of this kind of approach, especially its educational and preventive aspects, are described, and it is proposed as a possible model for interdisciplinary work that will help realize the goal of comprehensive health care.
The multiple relations between vision and touch: Neonatal behavioral evidence and adult neuroimaging data
Authors: Arlette Streri, Coralie Sann
Journal: Behavioral and Brain Sciences (2007)

Abstract Neonatal behavioral data support the argument that multiple relations exist between vision and touch. Looking at an object triggers the motion of a neonate's arm and hand towards it. A textured surface that is seen can be recognized tactilely, but not a volumetric shaped object in cross-modal transfer tasks. These data are supported by adult neuroimaging data.
Risk factors for primary biliary cirrhosis in a cohort of patients from the United States
Authors: Arti Parikh-Patel, Ellen B. Gold, Howard Worman, Kathryn E. Krivy, Eric M. Gershwin
Journal: Hepatology (2001)

Although the etiology of primary biliary cirrhosis (PBC) remains unknown, environmental factors may act to trigger the disease in genetically susceptible hosts. To assess specific risk factors, we conducted a survey using standardized NHANES questions to 241 PBC patients in the United States, 261 of their siblings, and 141 friends without PBC. The overall response rate was 199 of 241 (83%) among PBC cases, 171 of 261 (67%) among siblings, and 141 of 225 (62. 7%) among friend controls. The female-to-male ratio among cases in this sample was approximately 10:1; the mean age was 53 years, and 97% were Caucasian. Other autoimmune diseases reported most frequently by PBC cases included Sjogren's syndrome (17.4%) and Raynaud's syndrome (12.5%). Approximately 6% of cases reported at least one family member with PBC. Adjusted odds ratios (OR) were elevated for cases compared with friends for other autoimmune diseases (OR = 4.92, 95% confidence interval [CI] = 2.38, 10.18), smoking (OR = 2.04, 95% CI = 1.10, 3.78), tonsillectomy (OR = 1.86, 95% CI = 1.02, 3.39), and vaginal or urinary tract infection (UTI) in females only (OR = 2.12, 95% CI = 1.10, 4.07). Similarly elevated ORs were observed for these risk factors when cases were compared with their siblings. The higher rate of UTI among cases is particularly interesting in light of previous data, and raises the possibility of an infectious etiology for PBC and of molecular mimicry as an etiologic mechanism. The significance of smoking in the multivariate models supports the findings of previous studies and raises the issue of the influence of smoking on a Th1 response.
Human Scanning with ln-111 Oxine Labeled Autologous Lymphocytes
Authors: RICHARD MILGRAM, DAVID A. GOODWIN
Journal: Clinical Nuclear Medicine (1985)

Autologous lymphocytes were labeled with ln-111 oxine in 26 patients with chronic inflammatory disease. Whole body gamma camera scans were performed at 24 and 48 hours post injection. Activity was normally seen in spleen, liver, bone marrow, and cervical and inguinal lymph nodes; any activity outside there areas was considered abnormal. Five out of 11 patients with proven or suspected chronic osteomyelitis had positive scans. Four out of five patients with chronic arthritic diseases had positive scans. Also, three patients had bladder uptake suggesting bladder inflammation on a chronic basis.
Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation
Authors: Mohamed Chahine, Alfred L. George, Ming Zhou, Sen Ji, Weijing Sun, Robert L. Barchi, Richard Horn
Journal: Neuron (1994)

Mutations in the adult human skeletal muscle Na + channel a subunit cause the disease paramyotonia congenita. Two paramyotonia congenita mutations, R1448H and R1448C, substitute histidine and cysteine for arginine in the S4 segment of domain 4. These mutations, expressed in a cell line, have only small effects on the activation of Na+ currents, but mutant channels inactivate more slowly with less voltage dependence than wild-type channels and exhibit an enhanced rate of recovery from inactivation. Increase of extracellular pH made the rate of inactivation of RI 448H similar to that of R1448C, suggesting that this residue has an extracellular location and that its charge is important for normal inactivation. Analysis of single-channel data reveals that mutant channels inactivate normally from closed states, but poorly from the open state. The data suggest a critical role for the S4 helix of domain 4 in coupling between activation and inactivation.
The anguish of teenage mental illness
Authors: J. Pearce
Journal: BMJ (1997)

This Sunday at 7 30 pm Channel 4 screens The Madness of Children , a documentary that goes behind the scenes of an adolescent psychiatric unit in Manchester. Professor John Pearce says there is woefully inadequate provision for this age group. 

The title says it all. The Madness of Children confuses as much as it enlightens. What is madness? A good word to make people sit up and listen, but not very helpful as a description of a group of children who suffer from a range of disabling and potentially life threatening mental disorders. The producer, David Cohen, made Gorbachev's Asylums , and his documentary provides echoes of old mental asylums with shots of long green painted corridors, beds crammed too close …
Reading which FDG-PET images: Attenuation Corrected or Non Attenuation Corrected? A question forever
Authors: Jian Q. Yu, Simin Dadparvar, Hongming Zhuang, Abass Alavi
Journal: Clinical Nuclear Medicine (2005)

Greater New York and New England Chapters, the Society of Nuclear Medicine 18th Annual Northeast Regional Scientific Session Abstracts October 22–October 24, 2004—Stamford, Connecticut: PDF Only
Status of the Academic Worker
Authors: G. W. Harris
Journal: BMJ (1948)

<h3>Background</h3> Patients treated with immunotherapy are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Tumor mutational burden (TMB) has emerged as a promising predictive biomarker but requires tumor tissue which is not always available. Blood-based TMB (bTMB) may provide a minimally invasive assessment of mutational load. However, because of the required sequencing depth, bTMB analysis is costly and prone to false negative results. This study attempted to design a minimally sized bTMB panel, examined a counting-based method for bTMB in patients with stage I to IV non-small cell lung cancer (NSCLC) and evaluated both technical factors such as bTMB and tissue-based TMB (tTMB) cut-off, as well as sample-related factors such as cell-free DNA input mass which influence the correlation between bTMB and tTMB. <h3>Methods</h3> Tissue, plasma, and whole blood samples collected as part of the LEMA trial (NCT02894853) were used in this study. Samples of 185 treatment naïve patients with stage I to IV NSCLC were sequenced at the Roche Sequencing Solutions with a custom panel designed for TMB, using reagents and workflows derived from the AVENIO Tumor Tissue and circulating tumor DNA Analysis Kits. <h3>Results</h3> A TMB panel of 1.1 Mb demonstrated highly accurate TMB high calls with a positive predictive value of 95% when using a tTMB cut-off of 16 mut/Mb, corresponding with 42 mut/Mb for bTMB. The positive per cent agreement (PPA) of bTMB was relatively low at 32%. In stage IV samples with at least 20 ng of cfDNA input, PPA of bTMB improved to 63% and minimizing the panel to a subset of 577 kb was possible while maintaining 63% PPA. <h3>Conclusion</h3> Plasma samples with high bTMB values are highly correspondent with tTMB, whereas bTMB low results may also be the result of low tumor burden at earlier stages of disease as well as poorly shedding tumors. For advanced stages of disease, PPA (sensitivity) of bTMB is satisfactory in comparison to tTMB, even when using a panel of less than 600 kb, warranting consideration of bTMB as a predictive biomarker for patients with NSCLC eligible for immunotherapy in the future.
Progressive Myoclonus Epilepsies: Specific Causes and Diagnosis
Authors: Samuel F. Berkovic, Frederick Andermann, Stirling Carpenter, Leonhard S. Wolfe
Journal: New England Journal of Medicine (1986)

RECENT advances in the diagnosis and classifcxation of epileptic seizures and epileptic syndromes, together with improvemenss in anticonvulsant therapy, have enabled the great majority of patients with primary generalized epilepsy to be correttly diagnosed and successfully treated.1 2 3 4 In contrast, the secondary generalized epilepsies — that is, generalized epilepiies associated with a static or progressive encephalopathy — remain difficult to classify and to treat.4 5 6 7 Secondary generalized epilepsies account for approximately 9 percent of all patients with epilepsy seen by specialists.8 hhe onset of symptoms typically occurs in childhood, several types of generalized seizures are usually present, and evidence of cerebral damage . . .