tbuckley/cabot-search huggingface dataset:
Membrane diffusing capacity and pulmonary capillary volume in rheumatoid disease.
Authors: E A Hills, M Geary
Journal: Thorax (1980)

In some patients with rheumatoid disease gas transfer across the lungs is abnormal. We measured the membrane component of gas transfer (Dm) and pulmonary capillary volume (Vc) in 48 patients with rheumatoid arthritis and in 48 normal volunteers matched for age, sex, and smoking habits. Volunteers had normal chest radiographs and normal forced expiratory volume in one second and vital capacity. There were no significant differences between the rheumatoid and control groups for Dm. Mean Vc in rheumatoid male smokers (64.0 ml, SD 16.5) was significantly lower than in control male smokers (76.3 ml, SD 18.0 p less than 0.05). In rheumatoid female smokers mean Vc (43.4 ml, SD 13.3) was significantly lower than in rheumatoid female non-smokers (58.4 ml, SD 15.4 p less than 0.01). There was no significant difference between rheumatoid and control female non-smokers (mean Vc 58.4 ml and 60.7 ml respectively). Significant differences in Vc in terms of per cent predicted normal were found between patients receiving corticosteroids and those not receiving corticosteroids or penicillamine (p less than 0.02) and between patients with nodules and those without (p less than 0.05). Patients with persistently low transfer factor for five years had a significantly lower Vc (p less than 0.02). There was no consistent correlation between Dm and Vc and dynamic compliance or static recoil pressure. It appears that the abnormality of transfer factor in rheumatoid disease previously demonstrated is caused by reduction of Vc. It seems that involvement of pulmonary blood vessels occurs in patients with nodules and is suppressed by treatment with corticosteroids.
Gastrointestinal-Motility Dysfunction in Amyloidosis
Authors: William M. Battle, Marc R. Rubin, Sidney Cohen, William J. Snape
Journal: New England Journal of Medicine (1979)

SYSTEMIC amyloidosis frequently involves the gastrointestinal tract and may result in obstruction, malabsorption, ulceration, hemorrhage or perforation as well as impaired motility.1 2 3 It is unclear whether the impaired gastrointestinal motility is secondary to the effects of amyloid on the smooth muscle or on the autonomic nervous system. We report on a patient with primary amyloidosis, in whom esophageal manometric and colonic myoelectric studies revealed a widespread disorder of gastrointestinal motility. The evidence suggests that neural dysfunction contributes to the abnormal motility associated with amyloidosis.Case ReportA 68-year-old woman was admitted to the Hospital of the University of Pennsylvania with . . .
Case 6-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case A sixty-four-year-old woman entered the hospital because of hematuria and dysuria. Four years previously a simple cyst of the left kidney, 8 cm. in diameter, was demonstrated on an intravenous pyelogram (Fig. 1). The cyst was excised, and the patient remained well until four months before admission, when, after a routine pelvic examination, there was hematuria, with passage of clots and suprapubic pain for three days. Complete urinary obstruction ensued for twelve hours. Three days before entry hematuria again occurred, with dysuria and discomfort in the left flank. Physical examination showed a well nourished woman complaining of . . .
Induction of drug metabolizing enzymes in polybrominated biphenyl-fed lactating rats and their pups.
Authors: R W Moore, G A Dannan, S D Aust
Journal: Environmental Health Perspectives (1978)

Polybrominated biphenyls (PBBs) cause a mixed-type (phenobarbital- plus 3-methylcholanthrene-like) induction of liver microsomal drug metabolizing enzymes in rats. However, 2,2',4,4',5,5'-hexabromobiphenyl and 2,2',3,4,4',5,5'-heptabromobiphenyl, which together comprise less than 80% of PBBs (FireMaster), were shown to be strictly phenobarbital-type inducers. Other components (unidentified) must therefore cause the 3-methylcholanthrene-like effects. The potential for PBBs to exert effects on neonates through milk was examined. Lactating rats were fed 0, 0.1, 1.0, or 10 ppm FireMaster for the 18 days following delivery, at which time mothers and most pups were sacrificed. Pups nursing from mothers fed 10 ppm PBBs showed significant increases in liver weights and microsomal protein, and both mothers and pups had increased cytochrome P-450, aminopyrine demethylation, benzo[a]pyrene hydroxylation, and UDP-glucuronyltransferase. Pups nursing from rats fed 1.0 ppm had increases in microsomal protein, cytochrome P-450, aminopyrine demethylation, and benzo[a]pyrene hydroxylation, while their mothers were unaffected. Several pups from the 0, 0.1, and 1.0 ppm groups were maintained on their mother's diets, raised, and allowed to mate. Their pups showed much the same responses to PBBs as did the original group of pups. The effects on both generations of adult female rats were also comparable. PBBs cause a mixed-type induction in both lactating rats and their nursing pups; PBB components responsible for both aspects of this induction must be transmitted through milk. Nursing rats are approximately tenfold more sensitive to the effects of PBBs in their mother's diets than are the dams. The approximate no-effect level for microsomal induction in nursing rats is 0.1 ppm PBBs in the diet of the adult.
Sports medicine clinics on the NHS: a patient survey
Authors: S H Boyce, M A Quigley
Journal: British Journal of Sports Medicine (2001)

The football club doctor system EDITOR,-I read with interest the paper by Waddington et al 1 highlighting the inadequacies of the football club doctor system in Britain.This paper confirms the situation that many people already knew to exist.Advertisements for club doctors are rarely published in medical journals, doctors normally being appointed on a "who you know" basis.It is also particularly disappointing that, at a time when the specialty of sports and exercise medicine is being established in this country, the majority of doctors working with professional footballers have no qualifications or little experience in the specialty.However, this is not confined to football clubs and probably also applies to rugby clubs and many other sporting associations.One aspect not mentioned in the paper is medical litigation.It is to be hoped that doctors involved with football clubs have arranged medical defence cover, because, if a situation arises in which a player's sporting career is threatened by medical mismanagement and the doctor involved has no professionally recognised sports medicine qualification, he or she could be found guilty of medical negligence.With the amount of money involved in professional football, this could lead to dire consequences for the medical career of the practitioner involved.From a report commissioned by the Football League on the Hillsborough tragedy, the concept of the "crowd doctor" was introduced, meaning that any doctor involved in the medical care of the crowd at a football stadium would be required to possess at least the Diploma in Immediate Medical Care. 2 Before that, the situation was similar to that of the present club doctor system, and few doctors held any recognisable qualifications or training in medical emergencies and resuscitation.A similar recommendation by sports medicine authorities is required to enhance the quality of service provided to football clubs and increase the stature of the specialty.However, it is not a one sided situation.Football clubs must realise the importance of a medical team in looking after their prime assets, the players.Advertising of jobs in medical journals, insisting on experience and qualifications, adequate remuneration, and the provision of job descriptions and contracts should all be implemented.By working together to improve the current situation, a service can be provided in which both professional football players and the medical profession can have confidence.
Cytochrome a,a3 reoxidation. Early indicator of metabolic recovery from hemorrhagic shock in rats.
Authors: K Kariman, F F Jöbsis, H A Saltzman
Journal: Journal of Clinical Investigation (1983)

To assess the metabolic recovery of mitochondria after injury, we have monitored, in vivo and noninvasively, changes in the redox state of cytochrome (cyt) a,a3 in 35 rats after tissue hypoxia induced by rapid exsanguination to a mean arterial pressure of 30-35 mmHg. This level of mean arterial pressure was maintained for a shorter period of time in group I (n = 17) and a longer period of time in group II (n = 18), then the shed blood was returned by infusion. The surviving animals were observed for 2 more h before terminating the experiments. During exsanguination, reinfusion and recovery intervals brain tissue parameters of blood oxygenation, relative blood volume, and cyt a,a3 redox state were monitored continuously by spectrophotometry through the closed skull and intact skin. Group I had a high survival rate while group II had a very low survival rate. In both groups, with the onset of hypotension, there was a prompt rapid shift, followed by a slow continued progressive shift, of cyt a,a3 toward a more reduced state. The extent of recovery of cyt a,a3 following reinfusion was different in each group. In group I there was a rapid reoxidation of cyt a,a3 to a level above the base line (16 +/- 12%, mean +/- SEM). In contrast, the extent of reoxidation of cyt a,a3 in group II was significantly lower and stayed 31 +/- 6% below the base-line level. To further evaluate the mechanisms responsible for these observations, another related experiment was performed. 12 rats were subjected to shock and resuscitation as outlined for groups I and II. After death or killing of the animal, we measured, in vitro, oxygen consumption of cerebral cortical slices. Oxygen consumption of cortical tissue slices in subgroup I was significantly higher than in subgroup II. We conclude that, under these experimental conditions, the oxidative response of cyt a,a3 correlates closely with survival or death in the two groups. If in group I animals the greater oxidation of cyt a,a3, in vivo after resuscitation, reflects greater oxygen utilization, as is suggested by the in vitro observations in subgroup I, then we may be observing a useful adaptive response to tissue injury leading to preserved organ function and enhanced survival. Therefore, noninvasively measured cyt a,a3 redox state, reflecting intracellular metabolic activity, seems to indicate both the overall cerebral cellular response to injury and the likelihood of survival.
Fortnightly Review: Bone marrow transplantation
Authors: R. L Soutar, D. J King
Journal: BMJ (1995)

<h3>Summary points</h3> Bone marrow transplantation is becoming an increasingly used medical intervention Allogeneic bone marrow transplantation remains a risky medicalprocedure, with mortality about 30%, primarily from graft versus hostdisease and infection; autologous trans- plantation has a more acceptable mortality risk of 5–10% If results of ongoing trials in solid tumours are favourable autologous bone marrow trans- plantation may become a very common form of medical treatment Stem cells collected from peripheral blood are increasingly being used in place of conventional autologous transplantation; they lead to more rapid engraftment, reduce duration of hospitalisation, and may help to control costs As patient numbers increase, general practi- tioners will increasingly be confronted with the long term complications of bone marrow trans- plantation, such as infertility, secondary neo- plasms, and endocrine dysfunction Although most survivors of bone marrow transplantation do well after transplant, 25–50% of patients will have sexual, employment, and psychosocial problems
Placental-Blood Banking — A New Frontier in Transfusion Medicine
Authors: Leslie E. Silberstein, Leigh C. Jefferies
Journal: New England Journal of Medicine (1996)

Bone marrow has for years been the principal source of transplantable hematopoietic stem cells and progenitor cells. For bone marrow transplantation to succeed, it is crucial to find a donor whose HLA types match those of the recipient. If there is no suitable donor among the patient's siblings and relatives, most bone marrow–transplantation centers try to find one by searching a list of more than 2 million volunteers registered with the National Marrow Donor Program. Unfortunately, such inquiries identify matched donors for fewer than 40 percent of patients, and the probability of finding donors for patients from ethnic and racial . . .
Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells
Authors: Limor Zwi, Oren Caspi, Gil Arbel, Irit Huber, Amira Gepstein, In-Hyun Park, Lior Gepstein
Journal: Circulation (2009)

The ability to derive human induced pluripotent stem (hiPS) cell lines by reprogramming of adult fibroblasts with a set of transcription factors offers unique opportunities for basic and translational cardiovascular research. In the present study, we aimed to characterize the cardiomyocyte differentiation potential of hiPS cells and to study the molecular, structural, and functional properties of the generated hiPS-derived cardiomyocytes.Cardiomyocyte differentiation of the hiPS cells was induced with the embryoid body differentiation system. Gene expression studies demonstrated that the cardiomyocyte differentiation process of the hiPS cells was characterized by an initial increase in mesoderm and cardiomesoderm markers, followed by expression of cardiac-specific transcription factors and finally by cardiac-specific structural genes. Cells in the contracting embryoid bodies were stained positively for cardiac troponin-I, sarcomeric alpha-actinin, and connexin-43. Reverse-transcription polymerase chain reaction studies demonstrated the expression of cardiac-specific sarcomeric proteins and ion channels. Multielectrode array recordings established the development of a functional syncytium with stable pacemaker activity and action potential propagation. Positive and negative chronotropic responses were induced by application of isoproterenol and carbamylcholine, respectively. Administration of quinidine, E4031 (I(Kr) blocker), and chromanol 293B (I(Ks) blocker) significantly affected repolarization, as manifested by prolongation of the local field potential duration.hiPS cells can differentiate into myocytes with cardiac-specific molecular, structural, and functional properties. These results, coupled with the potential of this technology to generate patient-specific hiPS lines, hold great promise for the development of in vitro models of cardiac genetic disorders, for drug discovery and testing, and for the emerging field of cardiovascular regenerative medicine.
Clinical phenotypes and prognosis of patients with Common Variable Immunodeficiency (CVID) living in Rio de Janeiro, Brazil
Authors: A.J. Seba, N.P.M. Rubini, A.V. Capelo, E.M. da Silva, M.C. de Magalhaes, F.S. Sion, C. Morais-de-Sa
Journal: Journal of Allergy and Clinical Immunology (2012)
The Arterial Spider and Similar Lesions of the Skin and Mucous Membrane
Authors: WILLIAM B. BEAN
Journal: Circulation (1953)

The topic for the conference today will be the arterial spider of the skin' and other lesions of skin and mucous membrane which sometimes cause confusion in the minds of physicians.As back- ground for the discussion I will start with a short autobiographic note.This chronicle may help answer a question many students have asked me: "How did you get started in clinical research?"I do not recall having noticed or having had called to my attention the vascular spider of liver disease when I was an undergraduate student of medicine at the UUniversity of Virginia.When I was an intern on Dr. Longcope's service at the Johns Hopkins Hospital, both Dr. Longcope and Dr. Ham-
Increasing Antimicrobial Resistance and the Management of Uncomplicated Community-Acquired Urinary Tract Infections
Authors: Kalpana Gupta, Thomas M. Hooton, Walter E. Stamm
Journal: Annals of Internal Medicine (2001)

Community-acquired urinary tract infections (UTIs) are among the most common bacterial infections in women. Therapy for these infections is usually begun before results of microbiological tests are known. Furthermore, in women with acute uncomplicated cystitis, empirical therapy without a pretherapy urine culture is often used. The rationale for this approach is based on the highly predictable spectrum of etiologic agents causing UTI and their antimicrobial resistance patterns. However, antimicrobial resistance among uropathogens causing community-acquired UTIs, both cystitis and pyelonephritis, is increasing. Most important has been the increasing resistance to trimethoprim–sulfamethoxazole (TMP–SMX), the current drug of choice for treatment of acute uncomplicated cystitis in women. What implications do these trends have for treatment of community-acquired UTIs? Preliminary data suggest that clinical cure rates may be lower among women with uncomplicated cystitis treated with TMP–SMX when the infecting pathogen is resistant to TMP–SMX. Women with pyelonephritis also have less bacterial eradication and lower clinical cure rates when treated with TMP–SMX for an infection that is resistant to the drug. Therefore, in the outpatient setting, identifying risk factors for TMP–SMX resistance and knowing the prevalence of TMP–SMX resistance in the local community are important steps in choosing an appropriate therapeutic agent. When choosing a treatment regimen, physicians should consider such factors as in vitro susceptibility, adverse effects, cost-effectiveness, and selection of resistant strains. Using a management strategy that takes these variables into account is essential for maintaining the safety and efficacy of treatment for acute UTI.
P-Glycoprotein and Breast Cancer Resistance Protein: Two Dominant Transporters Working Together in Limiting the Brain Penetration of Topotecan
Authors: Nienke A. de Vries, Jin Zhao, Emily Kroon, Tessa Buckle, Jos H. Beijnen, Olaf van Tellingen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The brain is a pharmacologic sanctuary site, due to the presence of the blood-brain barrier (BBB). Whereas the effect of P-glycoprotein (P-gp) at the BBB is well established, the role of breast cancer resistance protein (BCRP) that is also expressed at the BBB is not. Experimental Design: We have studied the effect of BCRP by administering topotecan to wild-type (WT), single Mdr1a/b(−/−) and Bcrp1(−/−), and compound Mdr1a/b(−/−)Bcrp1(−/−) knockout mice. Drug levels in plasma and tissues were determined by high-performance liquid chromatography. Results: The area under the plasma and tissue concentration-time curve (AUC) of topotecan in brains of Mdr1a/b(−/−) and Bcrp1(−/−) mice was only 1.5-fold higher compared with WT mice, but in Mdr1a/b(−/−)Bcrp1(−/−) mice, where both transporters are absent, the AUC increased by 12-fold. The AUC in plasma was ∼0.75-, 2.4-, and 3.7-fold higher in Mdr1a/b(−/−), Bcrp1(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice, respectively, resulting in 2.0-fold (P &amp;lt; 0.01), 0.65-fold (P, not significant), and 3.2-fold (P &amp;lt; 0.01), respectively, higher brain-to-plasma AUC ratios. Results using Mrp4(−/−) mice showed that this transporter had no effect on the brain penetration of topotecan. The P-gp/BCRP inhibitor elacridar fully inhibited P-gp–mediated transport of topotecan, whereas inhibition of Bcrp1-mediated transport by elacridar was minimal. Conclusions: Our results using Mdr1a/b(−/−)Bcrp1(−/−) mice clearly show the effect of Bcrp1 at the BBB and also show how two drug transporters act in concert to limit the brain penetration of topotecan. We expect that this finding will also apply to other drugs that are substrates of both P-gp and BCRP. Consequently, to improve the brain penetration of such compounds for targeting intracranial malignancies in patients, it will be essential to use potent inhibitors of both drug transporters.
Ideas of Eighteenth-Century British Medical Writers about Anxiety
Authors: Mark D. Altschule
Journal: New England Journal of Medicine (1953)

THE present era has been termed "the Age of Anxiety," because many believe that anxiety is now more widespread than ever before. As pointed out below, the characterization is valid only if it is taken to mean that there is an intense preoccupation with anxiety in the twentieth century. There is no evidence that severe anxiety is more commonly experienced today than in earlier times; indeed, it is probable that the Age of Anxiety began with Adam, or perhaps earlier.A growing interest in anxiety as a symptom in emotional disorders was evident among Continental European writers of the late . . .
Intracellular Tracking of Single-plasmid DNA Particles After Delivery by Electroporation
Authors: Christelle Rosazza, Annette Buntz, Thorsten Rieß, Dominik Wöll, Andreas Zumbusch, Marie-Pierre Rols
Journal: Molecular Therapy (2013)

Electroporation is a physical method of transferring molecules into cells and tissues. It takes advantage of the transient permeabilization of the cell membrane induced by electric field pulses, which gives hydrophilic molecules access to the cytoplasm. This method offers high transfer efficiency for small molecules that freely diffuse through electrically permeabilized membranes. Larger molecules, such as plasmid DNA, face several barriers (plasma membrane, cytoplasmic crowding, and nuclear envelope), which reduce transfection efficiency and engender a complex mechanism of transfer. Our work provides insight into the way electrotransferred DNA crosses the cytoplasm to reach the nucleus. For this purpose, single-particle tracking experiments of fluorescently labeled DNA were performed. Investigations were focused on the involvement of the cytoskeleton using drugs disrupting or stabilizing actin and tubulin filaments as the two relevant cellular networks for particle transport. The analysis of 315 movies (~4,000 trajectories) reveals that DNA is actively transported through the cytoskeleton. The large number of events allows a statistical quantification of the DNA motion kinetics inside the cell. Disruption of both filament types reduces occurrence and velocities of active transport and displacements of DNA particles. Interestingly, stabilization of both networks does not enhance DNA transport. Electroporation is a physical method of transferring molecules into cells and tissues. It takes advantage of the transient permeabilization of the cell membrane induced by electric field pulses, which gives hydrophilic molecules access to the cytoplasm. This method offers high transfer efficiency for small molecules that freely diffuse through electrically permeabilized membranes. Larger molecules, such as plasmid DNA, face several barriers (plasma membrane, cytoplasmic crowding, and nuclear envelope), which reduce transfection efficiency and engender a complex mechanism of transfer. Our work provides insight into the way electrotransferred DNA crosses the cytoplasm to reach the nucleus. For this purpose, single-particle tracking experiments of fluorescently labeled DNA were performed. Investigations were focused on the involvement of the cytoskeleton using drugs disrupting or stabilizing actin and tubulin filaments as the two relevant cellular networks for particle transport. The analysis of 315 movies (~4,000 trajectories) reveals that DNA is actively transported through the cytoskeleton. The large number of events allows a statistical quantification of the DNA motion kinetics inside the cell. Disruption of both filament types reduces occurrence and velocities of active transport and displacements of DNA particles. Interestingly, stabilization of both networks does not enhance DNA transport.