tbuckley/cabot-search huggingface dataset:
Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration
Authors: Ulrich Gärtner, Richard J. Stockert, Anatol G. Morell, Allan W. Wolkoff
Journal: Hepatology (1981)

The normal rat hepatocyte divides approximately once per year but, following two thirds hepatectomy, rapid cellular replication occurs throughout the remaining liver remnant. Using a multiple indicator dilution technique, single-pass transport of 3 H-bilirubin and 125 I-asialoorosomucoid was studied in isolated perfused liver from 6hr to 6d after two thirds hepatectomy or sham surgery. Influx (k 1 ), efflux (k 2 ), and sequestration (k 3 ) rates were quantitated by computer analysis. k 1 for 3 H-bilirubin fell by over 50% within 6hr after two thirds hepatectomy and returned to normal 4d later. k 2 progressively decreased with a nadir at 2d, and returned to normal by 4d. k 3 was transiently depressed, and became normal within 2d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k 2 and k 3 parameters for best fit. Similar to results for 3 H-bilirubin, the k 1 of 125 I-asialoorosomucoid was 20% of normal at 1d after two thirds hepatectomy, and returned to normal by 6d. Unlike results for 3 H-bilirubin, there was a prolonged 50% reduction of k 2 and k 3 with return to normal by 6d. The transport changes during regeneration are independent of reduced liver mass or changes in hepatic spaces of distribution. The fact that influx of both compounds reaches a nadir at the time of greatest cellular proliferation with subsequent return to normal suggests a „maturation” of liver cell function for restoration of these specific hepatocyte functions. Modulation of the hepatocyte receptor for desialylated glycoproteins may also be required for cellular recognition as a prerequisite for proliferative responses.
Laboratory and pharmacological studies in man with hetacillin and ampicillin.
Authors: R. Sutherland, O. P. Robinson
Journal: BMJ (1967)

Lyell's Toxic Epidermal Necrolysis-Jefferson MEDICJOURNAL sidered likely in one case and possible in another.Nevertheless, it seems strange that such a specific disease pattern should suddenly be produced by the many different drugs recorded.As more reports appear, moreover, the incidence of cases due to drugs seems to diminish.In the present series of casesthe largest yet reported-it seems clear that the disease was not a septicaemia.On the contrary, my findings suggest that it is caused by phage-type-71 Staph.aureus, which produces a local skin condition, together with a secondary toxaemia, comparable to that produced by the streptococcus in scarlet fever.Possibly the staphylococcus produces an altered, potentiated, or new toxin, which in a non-immune person gives rise to toxic epi- dermal necrolysis.Though a search for rashes in other members of the household has not been made routinely, four cases were associated with impetigo, and, recently, routine nasal swabbing revealed phage type 71 in one parent in three different cases.Furthermore, the simultaneous involvement of two brothers and a sister, and the high incidence in children, would suggest an infection in those without resistance.Again, the geographical incidence supports infection, and a small region like Northern Ireland, with a population of under 1,000,000, has a relatively large number of cases, since 41 t have now been published and the number is undoubtedly higher. SummaryThirty-one cases of Lyell's toxic epidermal necrolysis are described.It is suggested that the condition starts as a local skin infection, followed by an extensive erythema and superficial exfoliation resembling scalding.This critical period of illness is succeeded by the sudden onset of recovery, reminiscent of the crisis course formerly seen in cases of pneumonia.Death occurred in a 3-day-old infant, but all other patients recovered completely without recurrence.The primary skin lesion was found to be caused by phagetype-71 Staphylococcus aureus, and it is postulated that the "'scalded skin syndrome" is due to a unique toxic effect of this organism.Thus, while a drug or other cause may be considered, a search for this organism is indicated in all cases.Treatment consists of skilled nursing together with the administration of antibiotics, systemic and topical; cortico- steroid drugs are not indicated.I am grateful to Dr. C. Field (consultant paediatrician) for inviting me to see several cases under his care, and for referring some cases to my unit.I am also indebted to Dr. F. F. Kane (consultant physician, Northern Ireland Fever Hospital) for allowing me to have details of Cases 4, 5, and 6.My thanks are also due to Mrs. Landau (senior scientific officer of the hospital laboratory) for her enthusiastic co-operation regarding
Public health director blows whistle on trust in letter to Lansley
Authors: M. Limb
Journal: BMJ (2012)

A leading public health doctor has sent a “whistleblowing letter” to the health secretary for England, Andrew Lansley, to condemn failures of financial management and corporate governance at an NHS trust that had racked up a £23m (€30m; $36m) deficit.

In his letter Peter Brambleby branded the response from the strategic health authority NHS London to an independent inquiry into accounting irregularities at NHS Croydon Primary Care Trust a “whitewash” and explained why he had quit his post and why he believed that more problems would surface.

Brambleby claimed that millions of pounds of public money remained “unaccounted for” and warned that underlying problems at the trust had not been fully acknowledged.

In the letter he said, “Not a single individual has accepted personal responsibility or shown they have learned.”

Brambleby said that he intends to take the “unprecedented” step of retracting certain chapters of two annual reports relating to programme budgets, saying …
Rational Asthma Therapy for the Outpatient
Authors: Renée K. Bergner
Journal: JAMA (1976)

ASTHMA has heterogeneous etiologies and mechanisms. New drugs, refined usage of old drugs, and anticipated release of still newer drugs render drug therapy in asthma more effective but more complex. Physicians caring for asthmatics should have a rational and practical understanding of the pharmacologic basis for its treatment. The management of asthma is primarily three-pronged: (1) identification of inciting allergens, irritants, or other underlying causes and their avoidance, if possible, (2) attention to ongoing hydration, and (3) medical management or drug therapy. Of the three, the first offers a potential "cure" and, therefore, should not be disregarded in favor of symptomatic therapy alone. The second is frequently neglected, though of importance in preventing status asthmaticus. The third offers a wide array of pharmacologic agents that allow adequate control for the majority of asthmatics—if drugs are prescribed<i>and taken</i>properly. The controversial role of allergy injection therapy in the management of
Transmission of Tuberculosis-Reply
Authors: Celina A. Pereira
Journal: JAMA (1976)

It is indeed true that the main mode of infection is by airborne tubercle bacilli and that pulmonary infection is, therefore, the most frequent. However, drainage from any focus of active tuberculosis can be a source of infection, and inhalation need not be the only way for the tubercle bacillus to gain entry in the human body. Ingested bacilli can create a primary focus in the intestinal tract, the tonsils, or the mucous membrane of the mouth. Tubercle bacilli that come in contact with broken skin can cause a primary complex of the skin; in pathologists performing postmortem examinations and butchers handling infected animal carcasses, the primary lesion was known to develop by direct inoculation. Urine of patients with renal tuberculosis is potentially infectious. Crowded home conditions and the presence of several very young children and an infant less than a year of age in the family are
Poor inpatient care for older people
Authors: S. G. Parker, S. Conroy
Journal: BMJ (2011)

Good care for frail older people should be part of mainstream clinical practice 

In 1963, in a message to Congress, John F Kennedy said that a society’s quality and durability can best be measured by the respect and care given to its elderly citizens.1 By this measure, the recent report from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) on the perioperative care of older people gives our society cause for concern.2 The report has been widely received as demonstrating inadequate care for older people undergoing surgery, and its findings described as shocking, disturbing, and unacceptable⇓.3



BSIP, LECA/SPL

The report describes an observational study of more than 800 patients over the age of 80 years who died within 30 days of a variety of surgical procedures. There was nothing extraordinary about these patients—they were typical in many ways of the population accessing acute care in the modern NHS. They were older; nearly all had comorbidity (94%); disabilities were common, as was delirium or dementia, or both; and many (66%) were identifiably frail. A key finding was that only …
Angiocrine Factors Deployed by Tumor Vascular Niche Induce B Cell Lymphoma Invasiveness and Chemoresistance
Authors: Zhongwei Cao, Bi-Sen Ding, Peipei Guo, Sharrell B. Lee, Jason M. Butler, Stephanie C. Casey, Michael Simons, Wayne Tam, Dean W. Felsher, Koji Shido, Arash Rafii, Joseph M. Scandura, Shahin Rafii
Journal: Cancer Cell (2014)
Filaggrin mutations are associated with ichthyosis vulgaris in the Bangladeshi population
Authors: C. Sinclair, E.A. O’Toole, D. Paige, H. El Bashir, J. Robinson, R. Dobson, N. Lench, H.P. Stevens, G.A. Hitman, R. Booy, C.A. Mein, D.P. Kelsell
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Ichthyosis vulgaris (IV) is an inherited skin disorder causing dry, scaly skin and affects approximately one in 250 people. Phenotypically, patients have palmar hyperlinearity, keratosis pilaris and fine scaling on the lower abdomen, legs and arms and symptoms usually manifest within the first year of life. Filaggrin (filament aggregating protein, FLG) is involved in the formation of the stratum corneum1, 2 and has been implicated in IV. Immunoblotting studies showed loss of profilaggrin expression in IV‐affected keratinocyte extracts compared with controls.3, 4 Keratohyaline granules, which contain profilaggrin, were found by electron microscopy to be absent in several patients with IV and markedly reduced in several others.5 In addition, mRNA of profilaggrin in patients with IV was found to be unstable and had a much shorter half‐life than controls.6 These early studies suggested that defective FLG was involved in the development of IV. Conclusive evidence for the role of FLG in IV was demonstrated when two mutations (R501X and 2282del4) in FLG were found to be associated with IV.7 These and other FLG mutations have also been shown to be associated with atopic eczema (AE).8–12 The pattern of inheritance of IV seems to be semidominant with homozygous and heterozygous FLG mutations underlying the severe and milder forms of IV, respectively. The association of FLG mutations with IV in Northern European and Japanese populations has been confirmed in subsequent studies.7, 9–13 The present report is the first to describe FLG mutation analysis in IV in an Indian subcontinent population, the Bangladeshi population residing in the East London area of the U.K.
Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.
Authors: R Mantegazza, F Andreetta, P Bernasconi, F Baggi, J R Oksenberg, O Simoncini, M Mora, F Cornelio, L Steinman
Journal: Journal of Clinical Investigation (1993)

Polymyositis is an inflammatory myopathy characterized by mononuclear cell infiltration of muscle tissue. Myocytotoxic T lymphocytes have been recognized in the infiltrates, but the muscle antigen, target of the immune attack, has not been identified. Molecular characterization of the variable regions of T cell receptors (TCRs) on the infiltrating lymphocytes can be expected to provide insights into the pathogenic process. The V alpha/beta TCR repertoire was investigated by RNA-PCR in muscle biopsies from 15 polymyositis patients and 16 controls (6 Duchenne muscular dystrophy and 10 with no inflammatory or dystrophic myopathy). A variety of rearranged variable TCR genes was found in polymyositis, V alpha 1, V alpha 5, V beta 1, and V beta 15 being the most common (present in 60-100% of patients). In Duchenne muscular dystrophy patients TCR V alpha or beta rearrangements were found although no restriction was observed; no rearrangements were found in muscles from the other controls. Sequence analysis revealed the presence of the J beta 2.1 region in 90% of the V beta 15 clones studied, no random N additions in the diversity region, and a common motif within the CDR3 region. These results suggest that selection of muscle-infiltrating T lymphocytes is antigen driven in polymyositis.
Basic Observations on the Physiology of the Human Myometrium During Pregnancy
Authors: Dhirendra Kumar
Journal: JAMA (1961)

DESPITE extensive research in muscle and reproductive physiology, the factors controlling the onset of labor are still far from clear. Experimental work in animals<sup>1-3</sup>has suggested that during pregnancy the myometrium overlying the placenta is inhibited and less excitable than interplacental myometrium, probably due to the local effect of placental progesterone. This difference, however, disappears at or near term allowing the uterus to contract in synchrony. Since the data obtained from animals may not necessarily be applicable to the human pregnant uterus, we have studied the comparative profiles in myometrium overlying the placental and antiplacental sites for ions, resting membrane potential, actomyosin-like protein, and the high-energy phosphates, adenosine-triphosphate (ATP) and phosphocreatine (PC), in human pregnancy for the first time. Biopsy specimens from women at various stages of pregnancy were obtained from the myometrium overlying the placental and antiplacental sites during elective cesarean section, cesarean hysterectomy and therapeutic abortion. Ionic
Osler and "House Pupil"
Authors: JOSEPH M. MOLINA
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 January 1985Osler and "House Pupil"JOSEPH M. MOLINA, M.D.JOSEPH M. MOLINA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-1-133_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I wish to compliment Dr. Hurst on his thought-provoking article (1) in which he uses a fictional visit by Sir William Osler as visiting professor to express his own views on the essential skills to be emphasized in training house officers. The fictional Osler states, "I like the name house pupil . . .Houseimplies that you remain in the hospital as though it is your home, andpupilindicates that you must remain a student of medicine forever." Osler would have agreed with this statement in principal, as he resided within the Johns Hopkins Hospital...References1. HURST J. Osler as visiting professor: house pupils plus six skills. Ann Intern Med. 1984;101:546-9. LinkGoogle Scholar2. CUSHING H. The Life of Sir William Osler. Oxford: Clarendon Press; 1925:317. Google Scholar3. OSLER W. Aequanimitas and Other Addresses. Philadelphia: Blakiston Co.; 1945:300. Google Scholar4. MYERS G. History of the Massachusetts General Hospital. Boston: Griffith-Stillings Press; 1929:31. Google Scholar5. CHESNEY A. The Johns Hopkins Hospital and the Johns Hopkins University School of Medicine: A Chronicle. Baltimore: The Johns Hopkins Press; 1943:161-2. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPreparation of chlorosulfonated polyethylene by the gas-solid method"House Pupils"J. WILLIS HURST, M.D. 1 January 1985Volume 102, Issue 1Page: 133-133KeywordsHospital medicine Issue Published: 1 January 1985 PDF DownloadLoading ...
A COMPARISON OF PHOTOTHERAPY, RADIOTHERAPY AND HIGH - FREQUENCY THERAPY IN SKIN DISEASES.
Authors: C. W. ALLEN
Journal: JAMA (1904)

it is sometimes very difficult to find the first scar which has produced a keloid.However, when we see a keloid on a cica¬ trix we call it a cicatricial keloid, which, on account of the in¬ filtration and of the running of the keloid, shows some differ¬ ences in its histopathologic structure.I think the maintenance of a distinction between cicatricial and spontaneus keloid is interesting and useful for the pathology and for history of this disease.As to thiosinamin, I note that Hebra used it a great deal, but at present it has been nearly abandoned.Re¬ cently Pere resorted to interstitial injections of 5 per cent, solution of creosotal in order to produce reabsorption of the tumor, but the results have been rather poor, and instead of seeing a diminution of the keloid they have seen it take larger proportions.I can not state what the relation is between tu¬ berculosis and keloid.In the cases I have had occasion to ob¬ serve I have found the patients in good physical condition, with no signs of tuberculosis.It may be that some cases have shown tuberculosis, but I think that is more of a coincidence than anything to do with the existence of a keloid.So I can say also with syphilis.I see a great deal of syphilis, but very rarely have I seen a case of keloid come on a syphilitic lesion.In regard to the elastic fibers, I believe they are lost only in those affections where we have a great deal of hypertrophy of the collagenous tissues, for instance, we often find in fibroma of the skin that very little elastic fibers remain.I believe the lack of elastic fibers is the secret of the formation of the keloid.
The effects of human herpesvirus 8 infection and interferon-γ response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals
Authors: F. Guedes, H.F. de Andrade Jr, E.R. Fernandes, F.F. Tuon, R.A. Brasil, C. Pagliari, M.I.S. Duarte
Journal: British Journal of Dermatology (2008)

Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary.To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS).We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART).CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS.Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.
Recovery of Adrenocortical Function during Long-term Treatment with Corticosteroids
Authors: L. Westerhof, M. J. Van Ditmars, P. J. Der Kinderen, J. H. H. Thijssen, F. Schwarz
Journal: BMJ (1970)

The recovery of adrenocortical function during very slow withdrawal of corticosteroids was studied in a homogeneous group of patients suffering from sarcoidosis. All patients had been treated with gradually decreasing doses of prednisone for at least two years. The initial dose had been 40 mg. daily in all cases. Determination of the cortisol production rate and of plasma fluorogenic corticosteroids was done under basal conditions and after tetracosactrin stimulation. There was good correlation between cortisol production rate and plasma fluorogenic corticosteroids throughout all the tests. Cortisol production rate and plasma fluorogenic corticosteroids started to rise when the dosage of prednisone was lowered to 7.5 mg. daily and reached normal values when the dosage was reduced to 2.5 mg. The response to tetracosactrin began to increase at the same dosage level, but was not normal at 2.5 mg., or when prednisone treatment was stopped. At a dosage level of 7.5 mg. of prednisone plasma fluorogenic corticosteroids already showed a nyctohemeral rhythm.It may be calculated that even very low dosages of prednisone given during the last stage of a treatment schedule enhance total corticosteroid activity beyond the normal level, which would account for their therapeutic value.
The Democrats' Last Ditch — Reconciliation or Bust
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2010)

The endgame has begun: with Republicans staunch in their opposition, the Obama administration and its congressional allies are poised to go it alone on a tortuous path toward enactment of ambitious health care reforms. To achieve their elusive goal, congressional Democrats may have to wield a controversial parliamentary maneuver and persuade 50 senators to vote for legislation designed to carry their reform bill to victory (Vice President Joseph Biden could then cast the 51st vote). But the first move in this three-step gamble is for the House Democratic leadership to persuade some of their more conservative colleagues who favor either . . .
Trial of niacin alongside statin is stopped early
Authors: J. Wise
Journal: BMJ (2011)

The US National Institutes of Health has stopped a clinical trial studying a combination of niacin (nicotinic acid) and a statin 18 months earlier than planned because of poor results.

The AIM-HIGH trial found that adding high dose, extended release niacin to a statin in patients with heart and vascular disease did not reduce the risk of cardiovascular disease and stroke. In fact there was a small and unexplained increase in ischaemic stroke rates among those receiving the combination treatment.

The randomised controlled trial involved 3414 patients in the United States and Canada with a history of cardiovascular disease who were already taking a statin drug to lower low density lipoprotein (LDL) cholesterol levels. The average age of the participant was 64 years and more …
The Adhesion GPCR GPR126 Has Distinct, Domain-Dependent Functions in Schwann Cell Development Mediated by Interaction with Laminin-211
Authors: Sarah C. Petersen, Rong Luo, Ines Liebscher, Stefanie Giera, Sung-Jin Jeong, Amit Mogha, Monica Ghidinelli, M. Laura Feltri, Torsten Schöneberg, Xianhua Piao, Kelly R. Monk
Journal: Neuron (2015)