tbuckley/cabot-search huggingface dataset:
250. Protection Against Huntington's Diease Progression: AAV-Mediated Delivery of Biotherapeutics
Authors: Adrian P. Kells, Rebecca A. Henry, Stephanie M. Hughes, Richard L.M. Faull, Bronwen Connor
Journal: Molecular Therapy (2006)

Advances in the development of adeno-associated viral (AAV) vectors for in vivo gene therapy have shown AAV vectors can safely direct the continuous, targeted production of biotherapeutics. This is promising for the treatment of neurological disorders like Huntington's disease where there is a delayed but progressive degeneration of the caudate-putamen. We have therefore investigated whether AAV-mediated in vivo gene therapy can effectively be used to deliver biotherapeutics and support vulnerable striatal neurons in a rodent model of Huntington's disease. Our focus is on brain- derived neurotrophic factor (BDNF) as a potential biotherapeutic, a protein important for general maintenance and functional plasticity of the striatum. We constructed a recombinant AAV vector with cDNA encoding human BDNF under the control of the chicken beta actin/CMV enhancer (CBA) constitutive promoter. The AAV expression cassettes are flanked by inverted terminal repeats from AAV serotype-2 and packaged using caspid proteins from both AAV serotype-1 and -2. Following AAV packaging we performed a protein assay with E15 primary striatal cells to check functional BDNF activity. Cells were transduced with AAV-BDNF and cultured in vitro for 3 weeks to allow neuronal differentiation. We observed a significant increase in calbindin positive neurons following AAV-BDNF transduction (P < 0.04) compared to the AAV-Luciferase vector indicating an increase in BDNF expression inducing neuronal differentiation towards a GABAergic phenotype. In vivo gene therapy was performed in adult male Wistar rats by stereotaxically injecting either AAV-BDNF (n = 12), AAV-Luciferase (n = 6) or vehicle solution (n = 6) into the striatum. We observed extensive AAV transduction and transgene protein expression within the striatum as well as the substantia nigra and globus pallidus due to anterograde transport of the vector via axonal projections. Three weeks following gene delivery the rats received a unilateral striatal injection of the neurotoxin quinolinic acid (50nmol) to model Huntington's disease cell loss. Forelimb use and sensorimotor neglect was analysed post lesioning to quantify motor function impairments between groups. The extent of neuroprotection was quantified by stereological analysis of DARPP-32 positive striatal projection neurons. We observed that BDNF over-expression within the striatum and projection nuclei provides protection against the excitotoxic cell death correlating with an alleviation of sensorimotor impairments. This study highlights the potential role of BDNF as an important biotherapeutic molecule for treating Huntington's disease and the use of in vivo gene therapy to limit neurodegeneration. Supported by Auckland Medical Research Foundation. A.P. Kells is a NZ FoRST Scholarship recipient.
Transient Stomatocytosis with Hemolysis: A Previously Unrecognized Complication of Alcoholism
Authors: CHARLES C. DOUGLASS
Journal: Annals of Internal Medicine (1970)

Four alcoholic patients developed hemolysis of varying severity. Both hemolysis and stomatocytosis appeared to be directly related to alcohol abuse, and both gradually disappeared while the patients were under hospital supervision. At least one of these patients seemed to have an intracorpuscular red cell defect. A survey indicated that peripheral smears from a minority of acute alcoholics contain an excess number of stomatocytes. This is the first description of transient stomatocytosis associated with acute alcoholism.
Role of emotional capacity in consent should be clarified
Authors: S. Moorhead
Journal: BMJ (2002)

EDITOR—Case law does not clearly distinguish between intellectual and emotional capacity. Sensky discussed the dilemma of withdrawing treatment but missed an opportunity to highlight the importance of emotional capacity in decision making.1

What constitutes a mental disorder that impairs capacity, making someone unable to understand emotionally (as opposed to intellectually) the personal relevance of information and weigh it up? The judge's perspective cited by Sensky is this: refusal by a mentally competent person to give consent is an absolute right even if the reason …
Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein analogues in the presence of calcium, phosphate and hydroxyl ions
Authors: Young Kyung Kim, Li-sha Gu, Thomas E. Bryan, Jong R. Kim, Liang Chen, Yan Liu, James C. Yoon, Lorenzo Breschi, David H. Pashley, Franklin R. Tay
Journal: Biomaterials (2010)
Sepsis-induced organ failure is mediated by different pathways in the kidney and liver: Acute renal failure is dependent on MyD88 but not renal cell apoptosis
Authors: J.W. Dear, H. Yasuda, X. Hu, S. Hieny, P.S.T. Yuen, S.M. Hewitt, A. Sher, R.A. Star
Journal: Kidney International (2006)
ATROPINE USED IN EYES DAILY FOR THIRTY-FOUR YEARS WITHOUT PRODUCING GLAUCOMA
Authors: Claude L. La Rue
Journal: JAMA (1928)

The case reported here is of interest because the pupils have been constantly dilated with atropine for the past thirty-four years without any increase in tension and without other harm to the eyes. A man, aged 52, came to the sanatorium because of kidney stones. During routine examination he was referred to the eye department because of widely dilated pupils and apparently cataractous lenses. The history of the eye condition was as follows: The patient had had congenital cataracts which during the first eighteen years of his life had caused very poor vision. At that age there had been an unsuccessful cataract extraction in the right eye without iridectomy. There was evidently postoperative infection and no improvement in vision. The surgeon prescribed atropine sulphate, 2 grains (0.13 Gm.) to the ounce (30 cc.), one drop daily in each eye, and advised cataract extraction in the left eye.
Artifactual Hypoglycemia: An Old Term for a New Classification
Authors: Valentina D. Tarasova, Mohsen Zena, Marc Rendell
Journal: Diabetes Care (2014)

The American Diabetes Association and The Endocrine Society workgroup on the 2013 classification of hypoglycemia (1) in patients with diabetes changed the previously used term “relative hypoglycemia” to “pseudo-hypoglycemia” while defining symptoms of hypoglycemia without confirmatory low glucose values and failing to include falsely low readings of glucose on capillary blood samples (1,2). In the past, pseudo-hypoglycemia was defined as a discrepancy between low capillary glucose and normal plasma glucose. We illustrate the current incongruity by reporting a case of a patient with Raynaud phenomenon with falsely low capillary blood glucose measured by finger stick.

A 75-year-old female with esophageal cancer post esophagectomy was found to have repeated asymptomatic low finger-stick blood glucose values varying from 11 to 53 mg/dL that were treated …
Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome
Authors: A. Gough, S. Chapman, K. Wagstaff, P. Emery, E. Elias
Journal: BMJ (1996)

demonstrating its superiority.At a time when health authorities around the country are "having regard to" the views of winners and losers as they rationalise acute services and close hospitals, it is a judgment which bodes ill for those who choose to go to law over the adequacy of public consultation.It is, if nothing else, a judgment well fitted to radical change.
Don't forget tuberculosis
Authors: F. Godlee
Journal: BMJ (2011)

Not so long ago tuberculosis was seen as an “old” disease, one that had been conquered in large parts of the world and might even be eliminated. No longer. HIV/AIDS, poverty, travel, and migration have seen tuberculosis re-emerge as a global pandemic. It now affects a third of the world’s population, and although there is optimism about reaching the millennium development goal target—that global incidence should be falling by 2015, no country or region has elimination realistically in its sights.

While most cases globally are in South East Asia, Africa, and the Western Pacific region, WHO says a pandemic is …
Pulmonary-Function Testing
Authors: Robert O. Crapo
Journal: New England Journal of Medicine (1994)

Pulmonary-function tests provide objective, quantifiable measures of lung function. They are used to evaluate and monitor diseases that affect heart and lung function, to monitor the effects of environmental, occupational, and drug exposures, to assess risks of surgery, and to assist in evaluations performed before employment or for insurance purposes. The indications for pulmonary-function tests are summarized in Table 1. Spirometric examination, the most widely used such test, is the focus of this paper. Spirometry is the measurement of the movement of air into and out of the lungs during various breathing maneuvers. Such examinations should be readily available and routinely . . .
Review: Intensive glucose lowering does not reduce mortality in type 2 diabetes
Authors: Vijaykumar Lingegowda
Journal: Annals of Internal Medicine (2011)

Source Citation Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. 21791495
THE EXCHANGES OF WATER, ELECTROLYTES AND HEAT DURING PHENYLETHYLHYDANTOIN SICKNESS 1
Authors: Fred V. Rockwell
Journal: Journal of Clinical Investigation (1935)

Phenylethylhydantoin (nirvanol) has been used since 1919 in the treatment of chorea minor.Its continued ingestion gives rise to a reaction, prob- ably of an allergic nature, which has been described by Ray and Cunningham (1) as follows: " The sedative effects of nirvanol usually appear on the second or third day of its administration.Fever develops on the seventh day, reaches a max- imum on the ninth day, and subsides on the elev- enth day.On the ninth day, a few reddish-brown maculo-papules appear on the thighs, wrists, or abdomen, the face often appears swollen and flushed, and a pale pink exanthem may appear on the soft palate or buccal mucosa.By the next day or two, the exanthem has become general.It is usually distinctly morbilliform, but some- what more like urticaria than the rash of measles.Leukopenia was observed in eight of nine cases.A marked eosinophilia was observed in all specimens of blood that were studied during the eruption."Nirvanol sickness bears a remarkable resem- blance to serum sickness.Rackemann, Longcope and Peters (2) studied the exchange of water and chlorides in pneumonia patients who had received horse serum, and they observed a marked transient retention of water and chlorides.Other in- vestigators (3) have at various times observed a similar retention of these substances in febrile diseases, notably lobar pneumonia.The present problem was undertaken in the hope that a con- trolled study of nirvanol sickness might indicate how general are the changes in metabolism during fever and allergic states.
1334 DYSREGULATION OF HOST INNATE IMMUNITY IN HCV GENOTYPE 1 INFECTED IL28B CT/TT HAPLOTYPE PATIENTS WITH DEPRESSED VIRAL KINETICS AND THERAPEUTIC RESPONSE
Authors: S. Naggie, A. Osinusi, A. Katsounas, R. Lempicki, E. Herrmann, B. Shivakumar, A. Thompson, P. Clark, K. Patel, A. Muir, J. Mchutchison, D. Goldstein, J. Schlaak, H. Masur, M. Polis, S. Kottilil
Journal: Journal of Hepatology (2011)
Hemolytic anemia in protoporphyria: Possible precipitating role of liver failure and photic stress
Authors: Nigel S. Key, Jeffrey M. Rank, Deborah Freese, Joseph R. Bloomer, Dale E. Hammerschmidt
Journal: American Journal of Hematology (1992)

Abstract Hemolytic anemia is not a common clinical feature in protoporphyria. In this report, we describe two patients in whom we have encountered severe hemolytic anemia. Both individuals had advanced hepatic disease as a complication of their porphyria and were undergoing orthoptic liver transplantation. The onset of hemolysis appeared to be related to the development of liver disease, and in both cases, the operative procedure acutely exacerbated the red cell destructive process. We suggest that liver involvement in protoporphyria may unmask hemolytic anemia, and that red cells in these individuals are hypersensitive to photooxidative stress, such as might occur during a prolonged operative procedure.
THE TREATMENT OF AMEBIC DYSENTERY WITH IPECAC BY RECTUM
Authors: GEORGE B. LAWSON
Journal: JAMA (1918)

Brem and Zeiler, 1 in 1911, successfully used ipecac by rectum and through the appendix after appendicostomy in several cases of amebic dysentery that had not yielded to other methods of treatment. This method does not seem to have come into any general use. We have been using a similar method for about five years, although, up until recently, we were ignorant of Brem and Zeiler's work. Our number of cases has been somewhat limited, and it is only in the past year that we have been able to test this method to our satisfaction. Our method of procedure is to put 60 or even 120 grains of powdered ipecac into about 24 ounces of water; this is kept hot for an hour, but not allowed to boil. After washing out the bowel with warm water, this whole preparation, without filtering, is given slowly by rectum to be retained as
Doctors, Patients, and the Need for Health Care Reform
Authors: Max Baucus
Journal: New England Journal of Medicine (2009)

One Montanan wrote to me recently about her father's death. Six months away from qualifying for Medicare coverage, he did not have health insurance or the cash to pay for recommended heart surgery. He died on Christmas Day.Since I began my current fight for health care reform 2 years ago, I have heard from hundreds of Montanans from across the state. So many of them tell heartbreaking personal accounts of tragedy and suffering that have resulted from our broken health care system. In nearly a century of effort, this country has never been as close as we are today . . .
Altered electrical and metabolic response of reperfused myocardium to ischaemia after recovery from preceding ischaemia: evidence for ischaemia sensitised myocardium
Authors: A. Nakagomi, T. Saito, Y. Kimura, Y. Tamura, M. Miura
Journal: Cardiovascular Research (1993)

Objective: The aim was to examine electrical and metabolic responses of myocardium to ischaemia after recovery from preceding ischaemia. Methods: In 23 open chest dogs (5 min occlusion group), the left anterior descending coronary artery was occluded three times in the following order: 2 rnin occlusion (Trial 1) followed by 15 rnin reperfusion; then 5 rnin occlusion followed by 90 rnin reperfusion and 2 rnin occlusion (Trial 2). In 15 control dogs, the 2 min occlusion was performed twice at a 110 min reperfusion interval; the former occlusion was also referred to as Trial 1 and the latter as Trial 2. The dogs were monitored by epicardial surface ECG, while regional myocardial function was estimated by sonomicrometry. Continuous measurements of myocardial tissue Pco2, pH, and extracellular K+ concentration were made concurrently. Results: Both trial occlusions produced a biphasic change in R wave amplitude characterised by a transient initial decrease succeeded by an increase with ST elevation. This biphasic change in R wave amplitude was indistinguishable between Trial 1 and Trial 2 in the control group. By contrast, in the 5 rnin group, the R wave amplitude initially decreased to a greater degree in Trial 2 than in Trial 1. More rapid contractile failure was also noticed in Trial 2, suggesting the possible involvement of mechanically induced electrical changes in the genesis of decreased R wave amplitude. After 45-60 s of occlusion, however, the R wave amplitude increased to a level much beyond the initial amplitude in Trial 1 [124.9(SEM 8.4% at 120 s], whereas this level of increase was not observed in Trial 2 [106.5(7.7)%, p<0.05 v Trial 1]. There was also reduced elevation of the ST segment in Trial 2: 3.6(0.8) mV v 6.5(0.8) mV Trial 1 at 120 s (p<0.05). This reduction in ST elevation was concomitant with decreased changes in Pco2, pH, and extracellular K+ concentration in Trial 2. These reduced changes in the ST segment and the metabolic variables were absent in the control group. Conclusions: These altered electrical responses of the myocardium may be the result of more rapid early contractile failure and attenuated metabolic changes during ischaemia occurring after recovery from preceding ischaemia. Cardiovascular Research 1993;27: 571-577
An acquired source of seizures
Authors: L. Azzopardi, J. Quirk
Journal: BMJ (2012)

A 35 year old man came to our hospital by ambulance after a first generalised tonic-clonic seizure witnessed by his wife, with further seizures in the ambulance. Earlier that day he had noticed transient left limb weakness with tremor. He had no symptoms of infection, headache, sore throat, or photophobia. He was independent, otherwise well, had no medical history of note, and was taking no regular drugs, although he had used steroids and protein supplements for body building purposes. He had moved to the United Kingdom from Nepal 12 years earlier but had not recently travelled. There were no other features in the history to suggest risk of immunosuppression.

On assessment, vital signs were within the normal range, with a temperature of 36.2°C. Cardiorespiratory and abdominal investigations were unremarkable. Neurological examination showed an unsteady gait but no neurological deficit. Full blood count, renal function, electrolytes, bone profile, liver function, C reactive protein, and retroviral testing were all normal. Figures 1⇓ and 2⇓ show neuroimaging scans. Lumbar puncture performed after brain scan showed an opening pressure of 20 cm of water, with normal cerebrospinal fluid biochemistry and negative microbiology analysis.



Fig 1 Post-gadolinium axial fluid attenuated inversion recovery (FLAIR) magnetic resonance image





Fig 2 Post-gadolinium coronal T1 weighted magnetic resonance image





### 1 What do the neuroimaging scans show?

#### Short answer

A solitary cystic lesion is seen at the junction of the right frontal and parietal lobes, with an eccentric nodule within.

#### Long answer

Magnetic resonance imaging shows a well defined lesion at the junction of the right frontal and parietal lobes, with a smooth thin rim of enhancement and a small amount of surrounding oedema (fig 3⇓). The lesion follows the …
Tobacco: deadly in any form or disguise
Authors: Peter Boyle, MA Yasantha Ariyaratne, Ruth Barrington, Harry Bartelink, Georg Bartsch, Anton Berns, Dominique de Valeriola, Ketayun A Dinshaw, Alexander MM Eggermont, Nigel Gray, Tadao Kakizoe, Balman Singh Karki, Miklos Kaslar, David J Kerr, David Khayat, Thiravud Khuhaprema, In-Hoo Kim, Jose Martin-Moreno, Gordon McVie, Jae-Gahb Park, Thierry Philip, Ulrik Ringborg, Alan Rodger, John R Seffrin, Vlacimir Semiglazov, Khee Chee Soo, Yun-tian Sun, Robert Thomas, Thomas Tursz, Umberto Veronesi, Otmar Wiestler, Keun-Young Yoo, Witold Zatonski, Ping Zhao
Journal: The Lancet (2006)
Alterations in c-fos expression, cell proliferation and apoptosis in pressure distended human saphenous vein
Authors: J Galea
Journal: Cardiovascular Research (1999)

Saphenous vein graft failures, resulting from thrombosis and the abnormal proliferation, migration and apoptosis of vascular smooth muscle cells (VSMC) are major limitations of coronary artery bypass surgery. We investigated whether surgical trauma of human saphenous vein induces the early response gene c-fos and causes alterations in rates of proliferation and apoptosis.Surgically prepared human vein consisted of distended (at 350 mmHg for 2 min) or non-distended segments of vein maintained in serum free RPMI at 37 degrees C and 5% CO2 for various time intervals. c-fos expression was detected by Northern analysis. Cell proliferation and apoptosis were determined by [3H]thymidine incorporation combined with proliferation cell nuclear antigen (PCNA) immunostaining and TUNEL, respectively. Labelling indices for proliferation and apoptosis were correlated with vessel was thicknesses.Control, freshly isolated vein expressed no c-fos. Surgically prepared vein synthesized c-fos 1 h following harvesting. There was a significant increase in c-fos in distended compared to non-distended vein. c-Fos protein increased in surgically prepared vein 24 h after harvesting. There was a significant increase in vascular cell proliferation in the non-distended compared to the distended vein: mean (S.E.M.) 1279 (218) vs. 863 (155) dpm/microgram DNA, P < 0.05, n = 6. In addition, the apoptotic index was significantly lower in the media of non-distended vs. distended vein 0.82 (0.2) vs. 5.5 (1.5), P < 0.05, n = 5.These findings demonstrate that surgical preparation of human saphenous vein increases expression of c-fos mRNA and apoptosis and reduces proliferation when compared with non-distended vein. These changes may influence the failure of saphenous vein grafts.
Hematologic Effects of Intrauterine Rubella
Authors: Aaron R. Rausen
Journal: JAMA (1967)

Six of 21 newborn infants with congenital rubella studied in 1964 and 1965 had hematologic abnormalities. These six infants had transient thrombocytopenic purpura with sparse numbers of megakaryocytes in the bone marrow. In addition, they had indications of partially compensated hemolytic disease. These included abnormalities of red blood cell morphology, transient anemia at the end of the first month of life, and normoblastemia, reticulocytosis, and erythroid hyperplasia of the bone marrow in the immediate neonatal period. Other stigmata of intrauterine rubella in these six infants included congenital heart disease, cataracts, intrauterine growth retardation, hepatosplenomegaly, histologic evidence of hepatitis, metaphysitis of the long bones, hypospadias, and cryptorchidism.
339. FIV Lentiviral Vector Gene Transfer for Hemophilia A
Authors: C.P. Chikkanna-Gowda, Litao Xie, Yubin Kang, Melissa A. Hickey, Patrick L. Sinn, Jessica D. Goreham-Voss, Steven W. Pipe, Paul B. McCrayJr
Journal: Molecular Therapy (2006)

Hemophilia A is an X-linked genetic disorder resulting in deficiencies in coagulation Factor VIII and a risk of sustained bleeding after trauma or injury. Hemophilia A is an attractive candidate for treatment by gene transfer because only partial correction is required for clinically relevant effects. We previously reported that gene transfer to the liver of E16 FVIII deficient mice using a lentiviral vector derived from feline immunodeficiency virus (FIV) resulted in sustained partial correction of the bleeding disorder. We are now investigating the impact of several vector and transgene modifications on gene transfer to hepatocytes using baculovirus GP64 pseudotyped FIV. The goals of the project are to improve transgene expression through several vector modifications and to test the optimized vector's effects on protein expression. Modifications include rendering the lentiviral vector "self-inactivating" by deleting the U3 region of the 3' LTR, inserting the FIV central polypurine tract (cPPT) element upstream of the internal promoter, and incorporating the woodchuck hepatitis virus posttranscriptional regulatory element (wPRE) downstream of a luciferase reporter gene or the FVIII cDNA. Furthermore, two sites were mutated, a major splice donor and the start codon of the partial Gag sequence, preventing production of undesired product. In addition, the post- transcriptional control element from the 5' LTR of spleen necrosis virus (SNVU5) was incorporated into the delivery vector. The liver- specific mouse albumin enhancer and human alpha-1-antitrypsin promoter (Alb/HAAT) are being used to direct firefly luciferase, B- domain deleted human FVIII (BDD-FVIII), and a FVIII cDNA engineered to include several asparagine-linked oligosaccharides within a short B-domain spacer (F226aa/N6) in wild type and E16 FVIII deficient mice on a congenic C57/BL6 background. Findings from these ongoing experiments will be reported.