tbuckley/cabot-search huggingface dataset:
Role of Calcium/Calmodulin-Dependent Protein Kinase II in the Regulation of Vascular Smooth Muscle Cell Migration
Authors: Rebecca R. Pauly, Claudio Bilato, Steven J. Sollott, Robert Monticone, Paul T. Kelly, Edward G. Lakatta, Michael T. Crow
Journal: Circulation (1995)

The migration of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of many vascular diseases. We have previously shown that VSMC migration in response to platelet-derived growth factor (PDGF) is suppressed when cultured cells are growth-arrested and induced to differentiate. The present study was undertaken to elucidate the mechanism of this suppression.While both proliferating and growth-arrested VSMCs upregulated expression of the immediate early response genes, c-fos and JE (monocyte chemoattractant protein 1), growth-arrested VSMCs exhibited much smaller changes in intracellular calcium in response to PDGF and failed to activate the calcium/calmodulin-dependent protein kinase II (CaM kinase II). Blocking calcium-calmodulin interactions (50 mumol/L W7) or the activation of CaM kinase II (10 mumol/L KN62) in proliferating cells blocked their migration by more than 90%, whereas inhibition of protein kinase C activation had no significant effect on migration. Pretreatment of growth-arrested VSMCs with the calcium ionophore ionomycin resulted in an approximately 2.5-fold activation of CaM kinase II and increased migration of growth-arrested cells to 84 +/- 6% that of proliferating cells. These effects of ionomycin were blocked by inhibitors of CaM kinase II. Constitutively activated (ie, calcium/calmodulin-independent) CaM kinase II introduced by gene transfection into growth-arrested cells significantly increased migration toward PDGF from < 20% to > 70% that of proliferating cells.These results demonstrate that activation of CaM kinase II is required for VSMC migration, that its activation in response to PDGF is suppressed in growth-arrested VSMCs, and that this suppression of CaM kinase II activation is responsible, in large part, for the failure of growth-arrested VSMCs to migrate toward PDGF.
Blair's billions: where will he find the money for the NHS?
Authors: J. Appleby
Journal: BMJ (2000)

This paper was first posted on www.bmj.com on 13 March 2000 

Government ministers have often committed to increased levels of NHS expenditure—but conditional on real growth in the economy as a whole. The prime minister's new spending pledge—to raise total (public and private) healthcare spending to match the European Union (EU) average as a proportion of gross domestic product by 2006—is largely independent of the performance of the economy.1 No matter how well the economy does, health spending must grow much faster to meet the pledged target.

Since this pledge, many have queried the arithmetic rigour of Tony Blair's calculations and the financial feasibility of hitting the target he has set, 2–4 It now seems that the government's interpretation of the EU average (8.0%) is wrong and that a more accurate figure is 9.0%. If this new figure is accepted, what are the options open to thegovernment in order to fulfil Blair's pledge?

#### Summary points

The prime minister has pledged to raise total UK healthcare spending by 2006 to match the European Union (EU) average as a proportion of gross domestic product (9.0% in 1997, not 8% as indicated by the prime minister)

All other things being equal, NHS spending would need to increase in real terms by 9.7% a year over five years (by £29.2bn in total) to reach the 9% target

There are three ways to increase healthcare expenditure: increased government spending, shifts in public spending towards the NHS, and increased private healthcare spending

Increasing taxes (such as 10p on the basic income tax rate or increasing VAT to 27%) or borrowing could fund the necessary increased spend but would be politically and economically unacceptable and could substantially increase government spending as a proportion of gross domestic product (from 39.7% to over 56%)

At one extreme, money …
Puerperal Cerebral Venous Thrombosis
Authors: J. Joseph
Journal: BMJ (1942)

saw the patient the next morning and agreed with the diagnosis.After discussion heparin therapy was tried, as it seemed to be a rational line of attack and it had previously given good results in cases of thrombophlebitis of'the lower extremities in the gynaecological ward.An intravenous drip of 5 % glucose saline was started, and was continued at the rate of a pint every four hours.Each pint contained 200 mg. of heparin, equivalent to 16,000 Toronto units.This therapy raised the blood coagulation time to over forty minutes, a con- siderably longer period than that recommended by McClure and Lam (1940).Heparin therapy was continued on the above lines for four days, by which time the patient had apparently fully recovered.A thrombophlebitis developed in the left leg on November 12 and in the right leg' on the 15th, while there was a return of the cerebral symptoms in a very mild form on the 17th.Further heparin treatment rapidly relieved these troubles.On November 23 septicaemic symptoms appeared and a blood culture revealed the presence of Staph.auireus.This infection was treated with sulphathiazole and staphylococcal antitoxin, and after twelve days of pyrexia and rigors the condition resolved.No heparin therapy was given on this occasion for fear of disturbing the normal mechanism of protective throm- bosis.A septic anaemia was dealt with by means of blood transfusions, and the patient was discharged, well, on December 24. Summary and ConclusionA review of the subject of puerperal cerebral thrombophlebitis' is given, and a case successfully treated by heparin is recorded.The introduction of heparin gives us an effective weapon to treat what has invariably been a fatal complication of the puer- perium, and the clinician's reward for an early diagnosis will be the survival of the patient rather than the sterile pleasure of making an accurate diagnosis and confirming it in the post- mortem room.
Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm.
Authors: D W Nebert, D D Petersen, A J Fornace
Journal: Environmental Health Perspectives (1990)

A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria.
Institutional Ethics Committees and the Shield of Immunity
Authors: Janet Fleetwood
Journal: Annals of Internal Medicine (1994)

Institutional ethics committees have been hailed as a good resource for physicians confronting complex ethical issues in patient care. Physicians may seek ethics committee consultations to receive impartial assistance in decision making, to resolve conflicts, and to avoid cumbersome court procedures and unwieldy litigation. The endorsement of ethics committees by the President's Commission, the American Hospital Association, the American Medical Association, and the Department of Health and Human Services, along with recent state legislation governing committees in Maryland, New Jersey, and Hawaii, raises questions about the proper scope and authority of ethics committees. We examined the accountability of institutional ethics committees and argue against immunity-conferring statutes that shield physicians who follow a committee's advice from civil and criminal liability.
Drug-facilitated sexual assault
Authors: M. M Stark, A R W Forrest, A Oyefeseo
Journal: Journal of the Royal Society of Medicine (2002)

Jason Payne-James and Deborah Rogers (July 2002 JRSM1) draw wider attention to a report2 identifying that many complainants of sexual assault have high concentrations of alcohol in their blood. In a Home Office report it was recommended that, when psychoactive drugs are involved, a clinical psychologist should testify as to the effects of the drug and that a toxicologist would be able to give evidence as to the complainant's behaviour against that of typical reactions to the drugs in question3. In the UK clinical psychologists are not necessarily trained in substance misuse and may never have seen an acutely intoxicated patient in a forensic setting as part of their practice. Thus clinical psychologists who are not specialists in addiction may not be able to advise investigators or provide evidence in court on the effects of drugs. Most toxicologists, except for a few who are medically qualified, cannot comment expertly on the clinical effects of drugs on an individual, although they may give helpful general advice on the effects of drug metabolites and level of toxicity.

In many cases the forensic physician who has attended the complainant shortly after the incident and who has taken a detailed history and performed a full examination will be the person in the best position to assist the court with an informed opinion, based on the objective results of an appropriate clinical examination, as to whether or not the complainant is intoxicated at the time of presentation. Furthermore his/her clinical findings will inform the analytical toxicologist's approach to the samples submitted to the laboratory. The opinion of a competent forensic physician as to which substances may have caused the signs exhibited and symptoms described by the complainant may be invaluable to the investigators and to the court, before the laboratory results have become available or in those cases where the complainant has presented too late for useful toxicological results to be obtained.

Clear recommendations have been issued to forensic physicians when called to examine complainants of sexual assault4 as well as for the toxicological investigation of such assaults5,6.
Whole-Body Hyperthermia Provides Biphasic Cardioprotection Against Ischemia/Reperfusion Injury in the Rat
Authors: Nobushige Yamashita, Shiro Hoshida, Naoyuki Taniguchi, Tsunehiko Kuzuya, Masatsugu Hori
Journal: Circulation (1998)

Background —Hyperthermia increases cardiac tolerance to ischemia/reperfusion injury 24 hours after the heat stress. Free radicals and redox mechanisms have been implicated in such tolerance. However, the time course and its relation to the induction of antioxidative enzymes in the protection induced by whole-body hyperthermia against ischemia/reperfusion injury are unknown. Methods and Results —Hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. After the defined recovery interval(s) at room temperature, ischemia was induced by occlusion of the left coronary artery for 20 minutes, followed by reperfusion for 48 hours. The exposure to hyperthermia led to a recovery interval– dependent, biphasic reduction in the incidence of ventricular fibrillation during ischemia and in the size of the myocardial infarct as determined after 48 hours of reperfusion. The time course of the late-phase (24- to 96-hour recovery interval) but not the early-phase (0.5 hour) cardioprotection depended on the degree of hyperthermia. The time course of the increase in myocardial manganese superoxide dismutase (Mn-SOD) activity corresponded to that of the cardioprotective effects, although an increase in the content of Mn-SOD and of heat shock protein 72 corresponded only to the late-phase effects. Administration of an antioxidant before hyperthermia abolished the early- and late-phase cardioprotection and the increase in Mn-SOD activity. Conclusions —The activation of Mn-SOD mediated by free radical production during hyperthermia is important in the acquisition of early-phase and late-phase cardioprotection against ischemia/reperfusion injury in rats.
Ecstasy and dantrolene.
Authors: P. J. Barrett
Journal: BMJ (1992)

At the time of Mrs Boyes's death the existence of paradoxical pain was recognised by only a few pain specialists.Consultants such as Dr Cox would certainly not have been expected to be aware of it.The choice presented to Dr Cox was stark: either to walk away from his patient and leave her to it or to do what he did.Mr Justice Ognall told Dr Cox that his choice was "a total betrayal of his unequivocal dutv as a physician."Most doctors faced with this dilemma may consider that Dr Cox did his medical duty despite the risk to himself.Mr Justice Devlin set out the rules for doctors in R v Adams."The doctor is entitled to do all that is proper to relieve pain and suffering, even if the measures he takes incidentally shorten life," but "if the acts are intended to kill, and do in fact kill, it is still murder."In practical terms doctors are allowed to assist death by giving large doses of morphine or heroin.But what if heroin, normally the strongest pain killing drug available, increases pain and there is no rationale for using other drugs?Paradoxical pain induced by heroin was not known in Devlin's time.Does his dictum need to be brought up to date?
Group calls for agency to boost UK bioscience industry
Authors: M. Gould
Journal: BMJ (2003)

A government backed working group has this week called for the creation of a national body to coordinate “mutually advantageous” partnerships between the NHS and the bioscience industry, which would speed the development of new treatments and generate income for patient care.

The Bioscience Innovation and Growth Team (BIGT) says a national clinical trials agency would be at the centre of a raft of financial and regulatory changes to ensure that UK bioscience can compete with the United …
A Large Cystic Lesion in the Left Posterior Parietal Region Demonstrated by Tc-99m HMPAO Brain SPECT Imaging
Authors: WEI-JEN SHIH, RICHARD S. HARTMAN, B H McQUAIDE, ELIZABETH NUGENT, VAL M. RUNGE, U YUN RYO
Journal: Clinical Nuclear Medicine (1992)

A large cystic lesion of the left cerebral hemisphere of a 15-year-old boy with a 6-year history of partial seizures was evaluated by both Tc-99m HMPAO and brain planar and SPECT studies. The images showed a large mass defect in the left posterior parietal region, which was confirmed by MRI imaging as a large cystic lesion consistent with congenital parencephaly. Despite a large brain involvement of the left hemisphere, uptake of both cerebellar hemispheres was symmetrical; there was no “crossed cerebellar diaschisis.” Tc-99m HMPAO planar images were as good as SPECT images.
Science and Clinical Medicine
Authors: Jeremiah A. Barondess
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In an editorial inThe Journalentitled "Are Medical Schools Neglecting Clinical Skills?" (236:861, 1976), Dr George L. Engel has, in his usual eloquent way, raised the vital issue of the impact of science and technology in medicine on the clinical tradition. In doing so, he has referred to an article of mine (<i>Arch Intern Med</i>134:150, 1974) and has suggested that it is my view that the effectiveness of the clinician is in some way divorced from the scientific method. There need be no doubt, I think, that the proper clinician indeed uses the scientific method, and that the best clinicians are those who do this most successfully. The fact that a clinician uses the scientific method does not, however, make him a scientist, and, in point of fact, it is precisely this confusion between the clinician and the scientist that is at the root of
How to Prevent Endoscopic Capsule Retention
Authors: B. Lewis
Journal: Endoscopy (2005)

Capsule endoscopy allows visual examination of the entire length of the intestinal mucosa in a noninvasive manner. Since its marketing release in 2001, it has become the gold standard in evaluating suspected disease of the small bowel [1] [2]. Having a capsule caught, trapped, or retained in the small bowel remains a major concern for physicians performing capsule endoscopy, since it could possibly lead to a need for surgery in a patient who would otherwise have been treated medically for the same illness. This has been thought to be apply in particular to patients with Crohn's disease or nonsteroidal anti-inflammatory drug (NSAID) enteropathy. In addition, it has been postulated that retention could cause acute small-bowel obstruction if the capsule became impacted in a stricture. Other causes of retention reported in the literature have included small-bowel tumors, radiation enteritis, and surgical anastomotic strictures. There is no clear medical therapy for these conditions, and surgical management of them has therefore limited concerns regarding capsule retention. Capsule retention has not been reported in so-called normal anatomy or anatomical variants such as colon or small-bowel diverticulosis and appendiceal orifices. Experience has shown that the risk of capsule retention is related to the indication for the examination. The rate of retention in patients with obscure gastrointestinal bleeding is 1.5 %, based on the reported 15 cases out of 1089 [3] [4] [5]. In patients with known Crohn's disease, the rate of retention is 5 %, based on four cases out of 80 [6] [7]. In patients with suspected Crohn's disease, the retention rate is 1.4 %, based on one case out of 71 [8] [9] [10] [11]. When capsule endoscopy was carried out in young healthy volunteers during a pharmaceutical trial, no cases of capsule retention were reported in 773 ingestions [12].
The Inevitable Failure of Current Cost-Containment Strategies
Authors: William B. Schwartz
Journal: JAMA (1987)

Current strategies for controlling hospital costs have focused primarily on eliminating care that is presumed to be of no medical value. These efforts have neglected the central fact that eliminating such care reduces current expenditures, but has little or no influence on three key factors responsible for the upward trend in real costs--population growth, rising input prices ("the hospital market basket"), and technologic innovation and diffusion. Aging of the population and the rising costs of malpractice insurance have received undue attention; together they can account for only three tenths of a percentage point in the upward trend. Gradual elimination of presumably useless care, perhaps as much as 30% of inpatient-days, can save many billions of dollars, but can only offset for a few years the forces causing costs to rise in US community hospitals. Indeed, in 1984, the reduction in patient days and resultant slowing in the real rate of rise to 2.1% appear simply to have concealed an underlying real rate of increase that was close to 7%. After all unnecessary days have been eliminated, the underlying rate of increase will reemerge unless limitations are placed on technologic innovation or beneficial services are rationed.
Effects of Autonomic Neuropathy on Coronary Blood Flow in Patients With Diabetes Mellitus
Authors: Marcelo F. Di Carli, Daniela Bianco-Batlles, Maria E. Landa, Andris Kazmers, Harvey Groehn, Otto Muzik, George Grunberger
Journal: Circulation (1999)

Background —Cardiac sympathetic signals play an important role in the regulation of myocardial perfusion. We hypothesized that sympathetically mediated myocardial blood flow would be impaired in diabetics with autonomic neuropathy. Methods and Results —We studied 28 diabetics (43±7 years old) and 11 age-matched healthy volunteers. PET was used to delineate cardiac sympathetic innervation with [ 11 C]hydroxyephedrine ([ 11 C]HED) and to measure myocardial blood flow at rest, during hyperemia, and in response to sympathetic stimulation by cold pressor testing. The response to cardiac autonomic reflex tests was also evaluated. Using ultrasonography, we also measured brachial artery reactivity during reactive hyperemia (endothelium-dependent dilation) and after sublingual nitroglycerin (endothelium-independent dilation). Based on [ 11 C]HED PET, 13 of 28 diabetics had sympathetic-nerve dysfunction (SND). Basal flow was regionally homogeneous and similar in the diabetic and normal subjects. During hyperemia, the increase in flow was greater in the normal subjects (284±88%) than in the diabetics with SND (187±80%, P =0.084) and without SND (177±72%, P =0.028). However, the increase in flow in response to cold was lower in the diabetics with SND (14±10%) than in those without SND (31±12%) ( P =0.015) and the normal subjects (48±24%) ( P &lt;0.001). The flow response to cold was related to the myocardial uptake of [ 11 C]HED ( P &lt;0.001). Flow-mediated brachial artery dilation was impaired in the diabetics compared with the normal subjects, but it was similar in the diabetics with and without SND. Conclusions —Diabetic autonomic neuropathy is associated with an impaired vasodilator response of coronary resistance vessels to increased sympathetic stimulation, which is related to the degree of SND.
SUBCUTANEOUS INJECTIONS OF OXYGEN IN THE TREATMENT OF BALANITIS GANGRAENOSA
Authors: RICHARD L. SUTTON
Journal: JAMA (1918)

Erosive and gangrenous balanitis, the balanoposthite erosive circinee of Berdal and Bataille, 1 is a fairly uncommon affection, even in large venereal clinics, but its serious character when unrecognized entitles it to more frequent and extended notice in medical literature than it has received up to the present time.  The disease is due to the symbiosis of a fusiform bacillus and a spirochete, which structurally resemble those found in Vincent's angina. The causative organisms were originally described by Muller and Scherber. 2 Culturally, they are anaerobic, and both stain readily with dilute carbolfuchsin, a tinctorial reaction which distinguishes the vibrio from the Spirochaeta pallida of Schaudinn and Hoffmann.  The lesions, which develop quickly on the glans or foreskin, usually are single, in contradistinction to chancroid, and do not give rise to inguinal adenitis. The pus is of a characteristic, foul odor. The local and constitutional symptoms vary with the severity
Trend and Variation in Treatment of Localized Prostate Cancer in the Southern Part ofThe Netherlands, 1988&amp;ndash;1996
Authors: Piet N. Post, Paul J.M. Kil, Ad J.M. Hendrikx, Philip M.P. Poortmans, Mariad A. Crommelin, Jan-Willem Coebergh
Journal: European Urology (1999)
Expression of E-Cadherin, β-Catenin, and Ki-67 in Goblet Cell Carcinoids of the Appendix: An Immunohistochemical Study with Clinical Correlation
Authors: Chiun Chei Li, Mitsuyoshi Hirokawa, Zhi Rong Qian, Bing Xu, Toshiaki Sano
Journal: Endocrine Pathology (2002)