tbuckley/cabot-search huggingface dataset:
Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection
Authors: Shanshan He, Billy Lin, Virginia Chu, Zongyi Hu, Xin Hu, Jingbo Xiao, Amy Q. Wang, Cameron J. Schweitzer, Qisheng Li, Michio Imamura, Nobuhiko Hiraga, Noel Southall, Marc Ferrer, Wei Zheng, Kazuaki Chayama, Juan J. Marugan, T. Jake Liang
Journal: Science Translational Medicine (2015)

Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.
Outcome of Patients With HIV Infection and Decreased Consciousness or Recurrent Seizures-Reply
Authors: Jean-Pierre Bédos
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Redosh believes that "neurological failure" is too imprecise and simplistic a term, given the complexity and diversity of neurological disturbances. This is indeed the case in a diagnostic setting, but not in the context of our prognostic study, which involved HIV-infected patients treated in an ICU. Our inclusion criteria were pragmatic and well suited to such patients in whom altered consciousness and convulsions are the two main neurological reasons for hospital admission. On admission to the ICU, altered consciousness was defined, regardless of the cause, as reduced consciousness requiring immediate intubation or likely to require intubation because of inability to handle airway secretions. In addition, recurrent convulsions or status epilepticus can necessitate emergent intubation and these were also included. We did not focus on patients with isolated neurological disorders (aphasia, hemiparesis, hemianopsia, and the like), who were not part of our cohort of patients admitted to the
Bilateral Hydrosalpinx with Torsion of Both Tubes
Authors: R. E. Shaw
Journal: BMJ (1949)

<h3>Objective</h3> Ethnic disparities in the use of total joint arthroplasty (TJA) may be attributed to differences in the clinical appropriateness to undergo TJA. We sought to determine if racial differences in clinical appropriateness for surgery existed among a sample of primary care clinic patients with moderately to severely symptomatic knee or hip osteoarthritis (OA). <h3>Methods</h3> We used the cross-sectional data of 684 patients who are potential candidates for TJA. Using a validated TJA appropriateness algorithm, an appropriateness factor was derived using the following variables: age (50–70 or &gt; 70 yrs), Charlson comorbidity (≤ 1 or &gt; 1), Western Ontario and McMaster Universities OA Index (WOMAC) pain and physical function, and adequacy of previous medical management. We used logistic regression to estimate the association of race with the dichotomous outcome of clinical appropriateness for TJA consideration. <h3>Results</h3> Sample consisted of 425 (62%) whites and 260 (38%) African Americans; 532 (78%) had knee OA and 153 (22%) had hip OA. The mean age was 64 ± 9 years and the mean body mass index was 33.6 ± 8 kg/m2. The mean overall WOMAC score was 56 ± 14 (range 30–96), suggesting moderately severe OA. There were no significant racial group differences (p = 0.3) in the proportions of those deemed clinically appropriate for TJA. After controlling for potential confounders, race was not a predictor of clinical appropriateness for TJA (odds ratio 1.2, 95% confidence interval 0.8–1.8, p = 0.3). <h3>Conclusion</h3> African Americans and whites were equally appropriate to be considered for TJA.
Violence in America: Guns
Authors: Phillip Kohanski
Journal: JAMA (1992)

<h3>To the Editor.</h3> —After reading the June 10, 1992, edition of<i>JAMA</i>, I am concerned with the manner chosen to address an important public concern, violence. Several articles dealt with the role that firearms play in violence and made inferences not necessarily based on fact. Mr Marwick<sup>1</sup>states, "The modern repeating pistol can hold 10, 15, or even more cartridges. In effect, it is a hand-held machine gun." It is inaccurate to consider any pistol that holds more than 10 bullets a machine gun. The inaccurate term was used to stir emotions, not to state facts. Mr Skolnick<sup>2</sup>quotes Representative Currie of the Illinois House of Representatives as saying, "A gun tax is the first step in reimbursing trauma centers that continue to treat gun-shot victims."<sup>2</sup>This makes as little sense as taxing hemophiliacs, drug addicts, prostitutes, homosexuals, and blood banks for the cost of AIDS care.
Test and treat for dyspepsia—but which test?
Authors: Cliodna McNulty, Louise Teare, Robert Owen, David Tompkins, Peter Hawtin, Kenneth McColl
Journal: BMJ (2005)

genic or mutagenic.Furthermore, these processes may reduce the efficacy of blood.For example, losses owing to tests and safety measures now reduce the red cell content of a blood pack by 10%, and some patients will therefore require more units, adding to the risk.We think that these large and recurring expenditures on blood safety should be balanced against the costs of the clinical trials still needed to provide an adequate evidence base for the use of transfusion, alternatives, and avoidance strategies.The decisions should involve a well informed public and be understood, and accepted, by them.
"The sarcoidosis map": a joint survey of clinical and immunogenetic findings in two European countries.
Authors: M Martinetti, C Tinelli, V Kolek, M Cuccia, L Salvaneschi, L Pasturenzi, G Semenzato, A Cipriani, A Bartova, M Luisetti
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We pooled immunogenetic data obtained in independent studies in two European populations (Italian and Czech) of patients affected by sarcoidosis. Correspondence analysis was used to investigate the associations between clinical and immunogenetic data. Two hundred and thirty-three patients were enrolled in the study, of which 126 were from the Czech Republic and 107 from Italy. Using a common protocol, we examined each patient for sex, age of disease onset, roentgenologic stage, extrapulmonary spread, and clinical course. One thousand and ten healthy individuals, HLA typed for class I and II serologic polymorphisms, served as controls. Findings that were essentially in agreement in both populations were: (1) a positive association of sarcoidosis with HLA-A1, B8, and DR3 markers, and a negative association with HLA-B12 and DR4; (2) a prevalence of HLA-DR3 and DR4 among females and of DR5 among males; (3) a relationship of B13 and B35 with early onset and of A30, B8, DR3, and DR4 with late onset of disease; (4) an association of B27 with sarcoidosis restricted to the lungs; (5) a relationship of A1, B8, B27, and DR3 to roentgenologic stage I and of B12 and DR4 to stage III; and (6) an association of HLA-DR3 with a good outcome. Population-restricted findings essentially concerned the alleles HLA-B13 and B22, the former being associated with the disease, male sex, early onset, extrapulmonary localization and relapse only in Czechs, and the latter to disease spread only in Italians. Our results seem to support the concept that immunogenetic background may at least partly account for the clinical heterogeneity of sarcoidosis.
Immune responses in Vietnamese children after a single dose of the auxotrophic, live Shigella flexneri Y vaccine strain SFL124
Authors: An Li, Phung Dac Cam, Dilara Islam, Nguyen Binh Minh, Pham Thi Huan, Zhao Chun Rong, Kerstin Karlsson, Gunilla Lindberg, Alf A. Lindberg
Journal: Journal of Infection (1994)
Clinical Pediatric Urology
Authors: John H. Fisher
Journal: JAMA (1977)

In this, the first textbook of pediatric urology compiled by full-time practicing pediatric urologists, the presentation is particularly directed to the clinical needs of the general urologist and pediatrician. The material has previously been dealt with in the form of a monograph, a volume in an encyclopedia, or a section in a textbook. The field of pediatric urology has grown so rapidly that more physicians limited their practice to this area, while other members of the profession have become increasingly aware of the frequency of genitourinary disease in the pediatric patient. The editors are well-qualified, authoritative leaders in this field, and the multiple-author format permits a balanced, comprehensive treatment without being encyclopedic or theoretical. The 29 chapters deal with general clinical evaluation and management and include specific sections on genitourinary anomalies, infection, and tumors. The special problems of the pediatric patient with renal failure are considered. Particularly useful to the
Validity of Laparoscopy after Abdominal Surgery
Authors: R. Orlando, F. Lirussi, L. Okolicsanyi
Journal: Endoscopy (1987)

The authors carried out a retrospective study to investigate the effect of previous abdominal surgery on the validity of laparoscopy. Laparoscopy was done in 2,000 patients with liver disease, between 1976 and 1985. Of these, 250 (12.5%) had undergone abdominal operations, and all presented with intraperitoneal adhesions. The whole surface of the liver was visible in 45.3%, but only in part in 46.2% of patients with upper abdominal operations (cholecystectomy, gastric surgery). Lower abdominal surgery (appendectomy, gynaecological operations) was associated with complete visibility of the liver in 97.5% of the cases. Laparotomy was followed by the highest incidence of non-visibility of the liver (28.5%). In the other 1,750 patients without abdominal operations, adhesions were detected only in 83 (4.1%) and the liver was entirely observable in 83.1% of these. In conclusion, previous abdominal surgery does not represent an absolute contraindication to laparoscopy, since risks are not as great as one might suppose. Although the view of the liver is sometimes impaired, laparoscopy retains its role in the assessment and therapy of liver disease, and avoids complications related to blind biopsy of the liver.
Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics
Authors: M. FARTASCH, I.D. BASSUKAS, T.L. DIEPGEN
Journal: British Journal of Dermatology (1992)

Journal Article Disturbed extruding mechanism of lamellar bodies in dry non‐eczematous skin of atopics Get access M. FARTASCH, M. FARTASCH Department of Dermatology, University of Erlangen, Germany Priv.‐Doz. Dr med M. Fartasch, Department of Dermatology, University of Erlangen. Hartmannstr. 14, 8520 Erlangen, Germany. Search for other works by this author on: Oxford Academic Google Scholar I.D. BASSUKAS, I.D. BASSUKAS Department of Dermatology, University of Erlangen, Germany Search for other works by this author on: Oxford Academic Google Scholar T.L. DIEPGEN T.L. DIEPGEN Department of Dermatology, University of Erlangen, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 3, 1 September 1992, Pages 221–227, https://doi.org/10.1111/j.1365-2133.1992.tb00118.x Published: 01 September 1992
Value of bromocriptine in unexplained primary infertility: a double-blind controlled trial.
Authors: C S Wright, S J Steele, H S Jacobs
Journal: BMJ (1979)

In a double-blind controlled study, 47 women with unexplained primary infertility were allocated at random to treatment with either bromocriptine 2.5 mg twice daily (24 patients) or placebo (23). Both groups showed a fall in serum prolactin concentrations but the reduction was much greater in the bromocriptine-treated group. Neither group showed a change in serum oestrogen or progesterone concentrations. Bromocriptine significantly reduced the duration of the follicular phase of the menstrual cycle but had no effect on the luteal phase. Five women conceived during treatment with placebo and seven during treatment with bromocriptine, but analysis of the cumulative conception rates showed no significant difference between the groups. The women who conceived were significantly younger and had a significantly shorter history of infertility than the women who did not conceive, but subtracting the number of years of infertility from age eliminated this difference. The results show that bromocriptine in the dose and duration of administration used in the trial is of no value in unexplained primary infertility.
Ectopic beta-adrenergic receptor binding sites. possible molecular basis of aberrant catecholamine responsiveness of an adrenocortical tumor adenylate cyclase.
Authors: L T Williams, T B Gore, R J Lefkowitz
Journal: Journal of Clinical Investigation (1977)

The molecular basis for the aberrant catecholamine responsiveness of the adenylate cyclase of adrenocortical carcinoma 494 was explored. The adenylate cyclase of this corticosteroid-producing, transplanted, adrenal cancer of the rat was stimulated not only by adrenocorticotropic hormone and fluoride, but also by the beta-adrenergic agonist, isoproterenol. The adenylate cyclase of normal adrenal tissue was unresponsive to isoproterenol. Direct binding studies with the specific high affinity B-adrenergic ligand, (-)[3H]dihydroalprenolol, demonstrated the pressure of 0.094 pmol of specific binding sites per milligram of tumor membrane protein. By contrast, normal adrenal membranes contained too few binding sites to accurately measure and study using these techniques. The tumor binding sites had high affinity for (-)[3H] dihydroalprenolol with an equilibrium dissociation constant of 2.1 nM. Adrenergic agonists competed for the binding sites in an order of potency, [(-) isoproterenol greater than (-) epinephrine (-) norepinephrine], paralleling their order of potency as beta-adrenergic agonists. The beta-adrenergic antagonist, (-) propranolol, competed for binding, causing half-mzximal inhibition of specific binding at a concentration of 6 nM. The alpha-adrenergic antagonist, phentolamine, and several catecholamine metabolites and precursors did not effectively compete for the binding sites at high concentrations. Binding was stereospecific, the (+) stereoisomers of beta-adrenergic agonists and antagonists requiring 40- to 300-fold higher concentrations than the corresponding (-) stereoisomers to half maximally inhibit (-) [3H] dihydroalprenolol binding. These results indicate that adrenocortical carcinoma 494 membranes contain beta-adrenergic receptor-binding sites which are not normally present in membranes of adrenal tissue. These ectopic beta-adrenergic receptors presumably confer on the neoplastic tissue the catecholamine sensitivity of its adenylate cyclase.
PSYCHIATRIC OBSERVATIONS ON CONGENITAL AND ACQUIRED DEAFNESS : SYMBOLIC AND PERCEPTUAL PROCESSES IN DREAMS
Authors: JACK H. MENDELSON, LEONARD SIGER, PHILIP SOLOMON
Journal: American Journal of Psychiatry (1960)

Twenty-six deaf college students were interviewed in the language of signs and manual alphabet to obtain information concerning the symbolic and perceptual processes experienced in their dreams. It was found that the dreams of the congenitally deaf were vivid, brilliantly colored, and reported as frequent in occurrence. Usually the language of signs was the means of communication in the dream, but in dreams in which affect was prominent, primitive signs were often utilized. The characteristic differences in the dreams of the deaf were most marked in the congenitally deaf, less marked in those with acquired deafness before age 5, and least marked in those with acquired deafness after age 5. The relevance of these findings to superego formation, non-verbal communication processes, and recent observations in experimental sensory deprivation is discussed.
CT abnormalities of the pituitary in hyperprolactinaemic women with normal or equivocal sellae radiologically.
Authors: R T Jung, M C White, N B Bowley, G Bydder, K Mashiter, G F Joplin
Journal: BMJ (1982)

Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.
Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice
Authors: David Bending, Hugo De La Peña, Marc Veldhoen, Jenny M. Phillips, Catherine Uyttenhove, Brigitta Stockinger, Anne Cooke
Journal: Journal of Clinical Investigation (2009)

Th17 cells are involved in the pathogenesis of many autoimmune diseases, but it is not clear whether they play a pathogenic role in type 1 diabetes. Here we investigated whether mouse Th17 cells with specificity for an islet antigen can induce diabetes upon transfer into NOD/SCID recipient mice. Induction of diabetes in NOD/SCID mice via adoptive transfer of Th1 cells from BDC2.5 transgenic mice was prevented by treatment of the recipient mice with a neutralizing IFN-γ-specific antibody. This result suggested a major role of Th1 cells in the induction of disease in this model of type 1 diabetes. Nevertheless, transfer of highly purified Th17 cells from BDC2.5 transgenic mice caused diabetes in NOD/SCID recipients with similar rates of onset as in transfer of Th1 cells. However, treatment with neutralizing IL-17-specific antibodies did not prevent disease. Instead, the transferred Th17 cells, completely devoid of IFN-γ at the time of transfer, rapidly converted to secrete IFN-γ in the NOD/SCID recipients. Purified Th17 cells also upregulated Tbet and secreted IFN-γ upon exposure to IL-12 in vitro and in vivo in NOD/SCID recipients. These results indicate substantial plasticity of Th17 commitment toward a Th1-like profile.
Oral Manifestations of the Chronic Graft- v-Host Reaction
Authors: Brad Rodu
Journal: JAMA (1983)

The graft-v-host reaction (GVHR), a major complication of bone marrow transplantation, is a complex immunologic phenomenon with a diverse and often confounding presentation. After reviewing major systemic manifestations, this report details the clinical and pathological oral findings of chronic GVHR. The reaction is characterized clinically by a mucosal lichenoid keratosis. Pathological findings resemble mucosal lichen planus, and minor salivary gland show lesions similar to those of Sjögren's syndrome. These oral findings are potentially valuable in the early recognition and follow-up of chronic GVHR. The differential diagnosis includes viral infections and chemotherapeutic drug toxicity, but these can usually be eliminated from consideration by viral cultures and temporal correlation of symptoms, respectively.
Nonfunctioning Cystic Disease of the Parathyroid
Authors: TANEKAZU HARADA, KATSUTARO SHIMAOKA, YASUHIKO OKAMURA, RYO KAWANO, MAKOTO KATAGIRI, NOBUAKI OTSUKA, MASAO FUKUNAGA, RIKUSHI MORITA, OSAMU OZAKI, KUNIHIKO ITO
Journal: Clinical Nuclear Medicine (1987)

Nonfunctioning parathyroid cysts that mimic nodular diseases of the thyroid gland are believed to be rare. On conventional thyroid scintigrams, the majority of nonfunctioning parathyroid cysts show a peculiar V-shape configuration. Since most of these cysts arise from the inferior parathyroid gland and more often from the left side, the lower portion of the affected thyroid lobe is displaced upward and medially, resulting in characteristic findings on thyroid imaging. Three such cases are presented in detail, and the imaging from these and five other cases are also shown. In normocalcemic patients whose thyroid imaging shows a V-shape configuration, sonography, percutaneous needle aspiration, and determinations of parathormone and thyroglobulin in cystic fluid are recommended for establishment of the diagnosis.
Marketing of medicines in India
Authors: Chandra M Gulhati
Journal: BMJ (2004)

Informing, influencing, or inducing? 

India has a large pharmaceutical industry. A major expansion started in the early 1970s when the Indian government took two fateful decisions. Firstly, it decided to permit domestic manufacturers to produce generic versions of patented molecules without permission from overseas innovators—provided a different manufacturing process was employed. Secondly, small scale pharmaceutical units were eligible for huge fiscal incentives and state subsidies. The new policy led to an unprecedented growth of medicine makers. Today an estimated 17 000 pharmaceutical companies produce over 40 000 branded formulations, many times more than the rest of the world.

Since the industry has free access to medicines discovered abroad, there is little incentive to undertake research to make new drugs. Consequently, nearly all companies are engaged in vicious …