tbuckley/cabot-search huggingface dataset:
Presence of HPV in later life may represent reactivation, not reinfection
Authors: B. Roehr
Journal: BMJ (2012)

Recurrent human papillomavirus (HPV) infection in women seen around the time of menopause may represent the reactivation of an old infection acquired decades earlier, rather than a new exposure, says a new study.1

Epidemiological studies worldwide have found two peaks of HPV infection in women. The first occurs a few years after sexual debut, followed by clearance of the infection in a significant proportion of women. The incidence during this peak correlates with the number of sexual partners.

The second peak occurs …
Resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire.
Authors: D Wright, J Bannister, M Ryder, A F Mackintosh
Journal: BMJ (1990)

To investigate the results of resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire.Study of all such attempts at resuscitation over 32 months, based on the standard report form for each call made by the ambulance staff and the electrocardiogram that showed the initial rhythm in each patient.Area covered by West Yorkshire ambulance service.1196 Patients with cardiac arrests attended by 29 ambulance staff with extended training.Result of resuscitation.The initial rhythm was asystole or electromechanical dissociation in 740 patients and ventricular fibrillation in 456 patients; overall 65 patients survived to be discharged from hospital. Sixty four of the 456 patients in whom ventricular fibrillation was the initial rhythm recorded, and 46 in whom ventricular fibrillation persisted after the ambulance staff arrived, survived. Only one of the 740 patients who initially had asystole or electromechanical dissociation survived. Factors associated with a greater chance of ventricular fibrillation occurring were: age less than 71, the arrest being witnessed by a bystander, resuscitation by a bystander, the arrest occurring in a public place, and a response time by the ambulance staff of less than six minutes. For patients found in ventricular fibrillation a shorter response time was associated with improved survival but resuscitation by a bystander was not. Additional skills learnt during extended training were used for 51 of the 65 patients who survived.Ambulance staff with extended training can save the lives of patients with cardiac arrest due to fibrillation, though asystole and electromechanical dissociation have a poor prognosis and should perhaps receive little attention during extended training.
SOME LESS FREQUENTLY CONSIDERED PORTALS OF INFECTION IN ARTHRITIS AND IRITIS
Authors: ERNEST E. IRONS
Journal: JAMA (1923)

The general principle that recurrent metastatic infections may result from chronic local infections seems well established, and the search for chronic hidden infections has become routine in the examination of patients, particularly those afflicted with arthritis and iritis. In many cases the removal of such chronic local infections is followed by freedom from recurrences of the metastatic lesions in eyes or joints, and the relief of the patient from his disability. In other cases, in many of which the clinical appearances of the lesions in the joints are indistinguishable from those of the favorable group, the removal of chronic local infections, if found, fails to free the patient from recurrent lesions, and the disease progresses. While much has been accomplished in the treatment of arthritis and similar metastatic infections, the study of the symptomatology and mechanism of chronic infections is by no means complete, and offers an interesting field for
Abstract 2453: Optimizing a modular synthetic approach for producing SH7139, a new drug candidate for treating B-cell lymphomas.
Authors: Monique Balhorn, Saphon Hok, Rod Balhorn
Journal: Cancer Research (2013)

Abstract The scale-up of synthetic methods for producing small molecule therapeutics can often prove to be problematic and expensive. Synthetic mechanisms can be inefficient and purification methods used to select specific isomers or remove reactants or other contaminants can often be difficult to scale. The modular approach we developed for creating small molecule targeting agents called SHALs (Selective High Affinity Ligands) as therapeutics and diagnostics for B-cell lymphoma circumvents many of these problems by using off the shelf components as “recognition elements” that collectively contribute to the molecules high affinity and selectivity and miniPEG and common amino acids to build up the scaffold using solid phase chemistry. Here we present the results of our efforts to scale up the synthesis of the first of these promising new drug candidates, SH7139, to provide the compounds needed for pre-IND animal testing and a pet dog lymphoma clinical trial. Working with AmbioPharm Inc,, a CRO with extensive expertise in the GMP synthesis of peptide pharmaceuticals, we recently completed small pilot production scale syntheses of SH7139 and several closely related analogs. The simple solid phase peptide-based chemistry used to synthesize the compounds coupled with preparative HPLC adapted well to scale-up and resulted in the production of highly purified compounds identical in structure (as determined by mass spectrometry and nuclear magnetic resonance spectroscopy) to the bench scale syntheses we performed in house. However, one unexpected and notable difference between the scaled-up synthetic products and their bench-scale synthesis counterparts was their solubility. SH7139 and two of its analogs, which are essentially insoluble in water and PBS when synthesized in house, were observed to be highly soluble (&amp;gt;100mg/ml) when synthesized using the scale-up protocol. While the reason for this is still under investigation, microscopic analyses of the dried product suggest the solubility difference may relate to the lyophilization step used to produce the dried product. The majority of the insoluble SH7139 we produce in bench-scale syntheses is amorphous in form, while the soluble SH7139 produced by AmbioPharm appears to be in a semi-crystalline or glass-like state. This research was supported, in part, by NIH/NCI SBIR grant 1R43CA159843-01 to Rod Balhorn. Citation Format: Monique Balhorn, Saphon Hok, Rod Balhorn. Optimizing a modular synthetic approach for producing SH7139, a new drug candidate for treating B-cell lymphomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2453. doi:10.1158/1538-7445.AM2013-2453
Coupling of Mutated Met Variants to DNA Repair via Abl and Rad51
Authors: Suganthini S. Ganapathipillai, Michaela Medová, Daniel M. Aebersold, Paul W. Manley, Sylvie Berthou, Bruno Streit, Wieslawa Blank-Liss, Richard H. Greiner, Barbara Rothen-Rutishauser, Yitzhak Zimmer
Journal: Cancer Research (2008)

Abstract Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Met, but not the wild-type form of the receptor, directly couple to the Abl tyrosine kinase and the Rad51 recombinase, two key signaling elements of homologous recombination–based DNA repair. Treatment of cells that express the mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant-dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a radiosensitizer together with the p53 inhibitor pifithrin-α by increasing cellular double-strand DNA break levels following exposure to ionizing radiation. Finally, we propose that in order to overcome a mutation-dependent resistance to SU11274, this aberrant molecular axis may alternatively be targeted with the Abl inhibitor, nilotinib. [Cancer Res 2008;68(14):5769–77]
Endomyocardial Fibrosis in Britain
Authors: M. Black, J. M. Fowler
Journal: BMJ (1965)

Fibrosis of the endocardium and myocardium, in the absence of disease of the coronary arteries, still receives scant attention in the standard medical textbooks.It has been recognized for many years as a comparatively uncommon complication of collagen diseases, infiltrative diseases (amyloid, haemo- chromatosis, von Gierke's disease), beriberi, Friedreich's ataxia and the muscular dystrophies, and alcoholism.The whole subject was well reviewed by Brigden (1957) in the St. Cyres Lecture of 1957.Its existence, in the absence of such associated diseases, was first recognized as a cause of heart failure in East Africans when Bedford and Konstam (1946) described the condition.Following this publication further series were contributed from South and Central Africa (Becker et al., 1953;O'Brien, 1954; Davies and Ball, 1955), and were thought to delineate a disease process peculiar to the African continent.Pathologically these cases were characterized by a fibrosis of the endocardium and myocardium with a reasonably constant distribution, and occasionally associated with a cellular infiltrate or a fibrinoid change in the smaller coronary arteries.However, these last two features were by no means a con- stant finding.That this condition has a world-wide distribution is only now becoming apparent.
Prognosis of new and worsening angina pectoris.
Authors: B Duncan, M Fulton, S L Morrison, W Lutz, K W Donald, F Kerr, B J Kirby, D G Julian, M F Oliver
Journal: BMJ (1976)

The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated.
The Population Explosion and the Future Number of Mental-Hospital Inpatients
Authors: Thomas F. Pugh
Journal: New England Journal of Medicine (1964)

THE age of people in Massachusetts, as in the United States as a whole, is presently undergoing radical change.Since both the type and number of patients coming to psychiatric attention differ at different ages it is essential to have knowledge about past and present changes in the size of the population according to age and to project future changes in its size specifically by age. Only in this way can sensible plans be made to provide the amount and type of psychiatric services desired.A major concern of the Massachusetts Department of Mental Health is the existing colossal growth . . .
Urinary Retention Following Cannabis Ingestion
Authors: Timothy A. Burton
Journal: JAMA (1979)

WITH growing public acceptance of cannabis, use of this drug has spread to the older segment of the population. Although age brings certain rewards, it also brings a generalized decline in the functional reserve of most organ systems. It therefore seems reasonable to expect that this population will show more adverse reactions to cannabis. <h3>Report of a Case</h3> A 55-year-old man was referred for psychiatric evaluation because of depression and persistent low-back pain without physical or roentgenographic findings. He had been a moderately severe alcoholic for approximately 33 years. He stopped drinking altogether after he began smoking cannabis daily at age 50 years. Psychotherapy began in the spring of 1975, and his depression gradually lifted. The major psychiatric problem then appeared to be his passive-aggressive personality. Between November 1976 and August 1977, he ate leftover cannabis butts in the evening on four occasions. Each time, he awoke in the morning
Casual Discovery of Tc-99m MDP Uptake for Melanoma Metastasis in Soft Tissue
Authors: G. RUBINI, F. LAURIERO, D. RUBINI, A. DʼADDABBO
Journal: Clinical Nuclear Medicine (1994)

The authors report the casual discovery in 1991 of a metastasis during Tc-99m MDP imaging of a 57-year-old woman who underwent surgery in 1983 for cutaneous melanoma on the right calf. The scan did not show bone alterations but did reveal an area of hyperactive uptake in the soft tissue of the medial surface of the thigh, where slightly altered pigmentation was also apparent. A subsequent immunoscan with Tc-99m-F(ab')2 225.28S confirmed increased uptake at this site. The lesion was removed and was histologically diagnosed as a skin metastasis from melanoma. Inguinal adenopathy appeared 6 months later. The uptake of Tc-99m MDP by both primary and metastases tumors has been described, although this may be the first report concerning melanoma. The uptake mechanism is not known.
Standardised program for medical audit is needed
Authors: E A S Nelson
Journal: BMJ (1994)

EDITOR, - A simple definition of medical audit, applicable to both developed and developing countries, is “the critical analysis of medical data to improve patients' care.” The type of analysis would depend on the detail and quality of the data available - that is, medical audit should be viewed as a maturing process, from the analysis of basic health statistics through to detailed analysis of the management of specific diseases and the use of resources.

My experience of setting up a system for collecting data in a developing …
Hepatitis B Transmission in a Family
Authors: William E. Mitch, Jack R. Wands, Willis C. Maddrey
Journal: JAMA (1974)

An epidemic of hepatitis B antigen (HB Ag)-positive viral hepatitis occurred in a large family and their acquaintances during a four-month period. Three adult members of the family had clinically apparent hepatitis and asymptomatic HB Ag-positive serum developed in the baby and grandmother. Two other family members were found to have antibody to hepatitis B. No one in the family but the index patient used illicit drugs parenterally but all had close contact with the index patient, the baby, and each other. This outbreak suggests means by which HB Ag may be transmitted by nonparenteral or inapparent parenteral routes in a family setting.
It is time to rethink juvenile idiopathic arthritis classification and nomenclature
Authors: Alberto Martini
Journal: Annals of the Rheumatic Diseases (2012)

<h3></h3> Juvenile idiopathic arthritis (JIA) is not a disease, but an exclusion diagnosis that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks, and are of unknown origin. This heterogeneous group of chronic arthritides has been classified on clinical and laboratory grounds to try to identify homogeneous, mutually exclusives categories suitable for etiopathogenic studies . Recent advances have shown that while some JIA categories identify quite definite disease entities, others still include heterogeneous conditions. Some aspects of JIA classification and nomenclature need therefore to be reconsidered.
Analgesic Supplements to Nitrous Oxide Anaesthesia
Authors: E. S. Siker
Journal: BMJ (1956)

MANIFESTATIONS OF MALIGNANT HYPERTENSION MEDICBALJOURNAL logical group; 27% of the patients suffered from epileptic seizures, but in almost half uraemia was present; 27 % had an abnormal mental state, usually associated with focal or generalized vascular lesions.Three-quarters had an acute vascular episode (focal ischaemia in 48%, intracerebral haemorrhage in 38%, and subarachnoid haemorrhage in 5.5%); and some had more than one type of lesion.Criticism is levelled at the frequent misuse of the term "hypertensive encephalopathy," which should be reserved for the syndrome as described by Volhard; it seems to be very rare, and was found in only one of our cases.An attempt should always be made to determine the cause of each cerebral event, and the term " focal brain ischaemia" used in appropriate cases.There were eight isolated cranial nerve palsies (facial nerve in seven, abducens in one).The C.S.F.pressure and contents were normal in 6 out of 42 cases.High pressure was found in 29, blood- staining in 11, and elevated protein content in 9 non- bloody fluids; some had more than one abnormality.Treatment appears to have prolonged life where severe renal damage was not present at the start of treat- ment.The survival in this group when untreated averaged less than a year.Ganglioplegic drugs seemed to be more effective than sympathectomy.We thank Professor J. McMichael
Right coronary artery occlusion: its role in the mechanism of precordial st segment depression
Authors: Hiroshi Sato, Kazuhisa Kodama, Tohru Masuyama, Shinsuke Nanto, Masatsugu Hori, Akira Kitabatake, Michitoshi Inoue, Takenobu Kamada
Journal: Journal of the American College of Cardiology (1989)
Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy
Authors: Man-Fung Yuen, Erwin Sablon, Chee-Kin Hui, He-Jun Yuan, Hilde Decraemer, Ching-Lung Lai
Journal: Hepatology (2001)

Factors associated with hepatitis B virus (HBV) DNA breakthrough and the significance of YMDD variants without the presence of wild-type YMDD during prolonged lamivudine treatment are unknown. We studied the amino acid sequence of codon 552 (YMDD motif) and codon 528 by means of a line probe assay in 159 chronic HBV patients (median follow-up 29.6 months). Pretreatment HBV DNA levels and alanine transaminase (ALT) levels correlated inversely with the time to HBV DNA breakthrough with YMDD variants ( r = −0.46, P = .001; r = −0.45, P = .001 respectively). Patients harboring YMDD variants 3 months before HBV DNA breakthroughs had higher HBV DNA breakthrough levels compared with those without YMDD variants 3 months before HBV DNA breakthroughs (18.9 × 10 6 vs. 5.4 × 10 6 copies/mL, P = .007). Patients with HBV DNA breakthroughs had higher percentages of YMDD variants without the presence of wild-type YMDD compared with patients without HBV DNA breakthrough (25.6% vs. 9%, P = .007 for single M552I variant; 20.9% vs. 8.1%, P = .026 for single M552V variant; 30.2% vs. 9.9%, P = .004 for M552I/M552V variants). Patients with HBV DNA levels of more than 10 3 copies/mL after 6 months of lamivudine therapy had a 63.2% chance of subsequently developing YMDD variants. HBeAg seroconversion occurred in 2 patients after the emergence of YMDD variants. Only one patient developed YMDD variant after HBeAg seroconversion. There was no increase in the rate of development of YMDD variants or L528M mutation in patients receiving lamivudine 25 mg daily or famciclovir 500 mg 3 times a day before being given lamivudine 100 mg daily.
Secrets of the dustbin
Authors: A. Jarvis
Journal: BMJ (2009)

It is well established that behavioral sensitization to psychomotor stimulants is associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed previously that the responsiveness of ventral tegmental area (VTA) DA neurons to glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats tested after 3 days of withdrawal, which suggests that adaptations in excitatory amino acid transmission also contribute to sensitization. The purpose of the present study was to determine the subtype of excitatory amino acid receptor responsible for this effect and to examine its persistence during withdrawal. Extracellular single cell recording and microiontophoresis were used to investigate possible alterations in the ability of glutamate agonists [(<i>S</i>)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), N-methyl-d-aspartate (NMDA), and (1<i>S</i>,3<i>R</i>)-1-aminocyclopentane-1,3-dicarboxylic acid (1<i>S</i>,3<i>R</i>-<i>t</i>-ACPD)] to stimulate the firing of VTA DA neurons after 3 days of withdrawal from repeated administration of saline, cocaine or amphetamine. Current-response curves showed that responses to iontophoretic AMPA, but not NMDA or 1<i>S</i>,3<i>R</i>-<i>t</i>-ACPD were significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons entered into a state of apparent depolarization block at significantly lower iontophoretic currents. When rats were tested for responsiveness to iontophoretic glutamate after 14 days of withdrawal, there was no significant difference between cocaine- or amphetamine- and saline-pretreated rats with respect to glutamate current-response curves. These results suggest that increased responsiveness of AMPA receptors on VTA DA neurons may contribute to sensitization at early withdrawal times, but that this alteration, like others described within the VTA, is transient.
Use and Effectiveness of Antimalarial Drugs
Authors: B. M. Nicol
Journal: BMJ (1953)

AFRICANS BRITNSH 177in human sera.It is, however, probable that as blood transfusion and serological testing become commoner in -Africans such' human antibodies will be found, and it is not improbable that there will be occasional clinical manifestations of incompatible blood transfusion and even of haemolytic disease of the newborn arising from the cor- responding antigen-antibody reactions.Summary An investigation has been carried out into the distribution in West Africa and the genetics of the Hunter antigen of Landsteiner, Strutton, and Chase (1934) and of the newly discovered Henshaw antigen.The genes for both of these antigens appear to be closely linked to those of the MNSs blood-group system.Thanks are due to the Rockefeller Foundation for a grant given to one of us (J.N. M. C.) in defrayment of part of the expenses.We wish to thank
Physiological importance of nitric oxide.
Authors: J Collier, P Vallance
Journal: BMJ (1991)

<h3>Introduction</h3> Sex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not been assessed in pathologically confirmed participants. <h3>Methods</h3> Core DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer’s Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden. <h3>Results</h3> In the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria. <h3>Discussion</h3> Sex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.
Screening for hepatocellular carcinoma in patients with Child's A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein
Authors: Mario Cottone, Miriam Turri, Maria Caltagirone, Pietro Parisi, Ambrogio Orlando, Germana Fiorentino, Roberto Virdone, Giorgio Fusco, Rossella Grasso, Rosa Giovanna Simonetti, Luigi Pagliaro
Journal: Journal of Hepatology (1994)