tbuckley/cabot-search huggingface dataset:
A New Approach to the Treatment of Leg Ulcers
Authors: D. B. Fox
Journal: BMJ (1962)

HYPOTHERMIAA rapid spontaneous rise in temperature is a good prognostic sign; thus all patients who survived had regained a normal temperature within 24 hours.We feel that if rewarming is to be used at all it should be restricted to those patients who have shown no significant rise in temperature by 24 hours.A prolonged period of hypothermia undoubtedly contributes to a very poor prognosis, and in this group active rewarming is justified.Hydrocortisone was given to all patients during the hypothermic period.Adrenocortical function is impaired in hypothermia and also in myxoedema (Hubble, 1955).Eghdahl et al. (1955) found that secretion of 17-hydroxycorticosteroids fell to 25% of control values in dogs cooled to 77-82°F.(25-27.8°C.) and that no increase was produced by infusion of adrenocorticotrophic hormone.It was noticed that in several of the present patients hypotension was more readily controlled after injection of hydrocortisone.Intravenous fluids were given when indicated, and mephentermine or meteraminol if hypotension was present, but noradrenaline infusion was ultimately required in Cases 2, 4, 7, and 8. Triiodothyronine 10 to 60 Mug.daily was given orally in Cases 1, 2, and 3.All patients received penicillin or tetracycline, with digoxin and thiazide diuretics if cardiac failure was present.It has been shown that digitalis is not contra- indicated in hypothermia and is not a factor in the origin of ventricular fibrillation (Angelakos et al., 1958).One patient (Case 5), although not cyanosed, had marked respiratory depression, and positive-pressure respiration was required for 12 hours. Summary and ConclusionsNine cases of accidental hypothermia seen in a small hospital within a period of four months are reported.Three patients survived.Electrocardiographic and biochemical abnormalities are briefly reviewed.It is suggested that the condition is by no means uncommon and should be considered in the differential diagnosis of all patients with impaired consciousness during the winter months.It can occur rapidly and is by no means confined to the elderly and neglected.Although there is often a history of exposure during cold weather, hypothermia can develop when the patient is in bed in relatively warm surroundings.The phenothiazine group of drugs should be given to the elderly and hypothyroid patient with caution and the rectal temperature checked if confusion or drowsiness occurs.This should be taken with a low-reading thermometer or, if unavailable, an ordinary lotion thermometer.The prognosis is poor, but is more favourable in the younger patients.
Impaired Endothelial Regulation of Ventricular Relaxation in Cardiac Hypertrophy
Authors: Philip A. MacCarthy, David J. Grieve, Jian-Mei Li, Christina Dunster, Frank J. Kelly, Ajay M. Shah
Journal: Circulation (2001)

Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved response to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in this defect.Short-term treatment with the antioxidants vitamin C (10 micromol/L) or deferoxamine (500 micromol/L) restored LV relaxant responses to the NO agonists bradykinin (10 nmol/L) and substance P (100 nmol/L) in isolated ejecting hearts of aortic-banded guinea pigs. Substance P decreased the time to onset of LV relaxation (tdP/dt(min)) by -6.8+/-1.7 ms in the presence of vitamin C and by -8.9+/-2.2 ms in the presence of deferoxamine compared with -0.8+/-2.2 ms in the absence of antioxidants (P<0.05 either antioxidant versus control). A similar restoration of relaxant response to substance P was observed in the presence of the superoxide dismutase mimetic, Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (10 micromol/L), but not with tetrahydrobiopterin or L-arginine. Protein expression of the NADPH oxidase subunits gp91-phox and p67-phox and myocardial NADPH oxidase activity were significantly increased (P<0.05) in the banded group compared with shams.An increase in ROS, most likely derived at least in part from NADPH oxidase, is responsible for the impaired endothelial regulation of LV relaxation in LVH. These are the first data to potentially link increased NADPH oxidase-derived ROS with a defect in cardiac contractile function in a pathological setting.
Postperinatal mortality in a health district with a garrison town.
Authors: A. Biswas, M. J. Dalton
Journal: BMJ (1988)

exertional rhinorrhoea inhalation of cold dry air elicited a mean threefold increase in symptom scores and a mean sixfold increase in histamine concentrations in lavage fluid, accompanied by significant increases of prostaglandin D2, leukotrienes, tosyl-L-arginine methyl esterases, and kinins.'2No change in mediator concentra-
Labour and Conservatives draw up battle lines on NHS
Authors: L. Eaton
Journal: BMJ (2002)

Britain's Labour government and the Conservative opposition party this week outlined their radically different approaches to the future funding of the NHS—with the government backing higher spending financed through public funding and the Conservatives favouring a social insurance based scheme.

On the eve of Chancellor Gordon Brown's budget speech on Wednesday, the Conservative leader, Iain Duncan Smith, produced a report supporting a healthcare system funded through social insurance—where employer and employee pay towards a compulsory health insurance plan—rather than a system funded through general taxation.

The policy shift by the Conservatives came as it became clear that the chancellor of the exchequer would make a radical move on NHS funding, announcing extra resources for the service on top …
Interactions Between Human Plasma Components and A Xenogenic Adenovirus Vector: Reduced Immunogenicity During Gene Transfer
Authors: Matthieu Perreau, Marie-Christine Guérin, Christian Drouet, Eric J Kremer
Journal: Molecular Therapy (2007)

By the time we are adolescents most of us have been in contact with several of the >50 human adenovirus (HAd) serotypes. These common subclinical infections lead to an efficient anti-adenovirus cross-reacting adaptive immunity. During gene therapy, the ubiquitous anti-adenovirus humoral response and complement activation will modify and dictate vector biodistribution, as well as the response to the virion and transgene(s). In this study, we assayed the interactions of a xenogenic adenovirus derived from canine serotype 2 (CAV-2) with naturally occurring human antibodies (Abs) and the complement system. In our cohort, we found class G immunoglobulins (Igs) that recognized the intact CAV-2 virion and the external virion proteins. However, the majority of donors had low or no neutralizing Abs, class A, or class M Igs. Purified anti-HAd serotype 5 Abs also recognized CAV-2 virion proteins. In addition, in spite of the presence of anti-CAV-2 IgGs, CAV-2 poorly activated the classical and alternative complement cascades. This atypical response was due to a block upstream of the component 3 (C3) convertase and interplay between the component 1 (C1) inhibitor, the C1q-C1r2-C1s2 complex and CAV-2. Our data demonstrate that some xenogenic adenovirus vectors, like CAV-2, could lead to notably different outcomes following systemic delivery.
Corticotropin-releasing factor. Mechanisms to inhibit gastric acid secretion in conscious dogs.
Authors: H J Lenz, S E Hester, M R Brown
Journal: Journal of Clinical Investigation (1985)

Immunoreactivity similar to that of corticotropin-releasing factor (CRF) is found in regions of the central nervous system that modulate autonomic responses, including gastrointestinal functions. We examined the central nervous system effects of ovine CRF on gastric acid secretion in conscious dogs. Male beagle dogs (11-13 kg) were fitted with chronic intracerebroventricular cannulae and gastric fistulae. Gastric acid secretion in response to intravenously administered gastric secretory stimuli was measured by in vitro titration of gastric juice to pH 7.0 and in response to an intragastric meal by in vivo intragastric titration at pH 5.0. Plasma gastrin was determined by radioimmunoassay. CRF microinjected into the third cerebral ventricle decreased pentagastrin-stimulated gastric acid secretion for 3 h (P less than 0.01) dose-dependently (0.2-6.0 nmol X kg-1). CRF did not inhibit histamine-stimulated gastric secretion but significantly (P less than 0.01) decreased the secretory response after 2-deoxy-D-glucose for 3 h. The gastric inhibitory action of intracerebroventricularly administered CRF on pentagastrin-stimulated gastric acid secretion was completely abolished by ganglionic blockade with chlorisondamine. The opioid antagonist, naloxone, and the vasopressin antagonist, [1-deaminopenicillamine,2-(O-methyl) tyrosine,8-arginine]-vasopressin, significantly suppressed the inhibitory effect of CRF on gastric acid secretion stimulated by pentagastrin. In contrast, truncal vagotomy did not prevent the inhibition of gastric acid secretion induced by CRF. CRF (0.2-2.0 nmol X kg-1) administered intracerebroventricularly decreased gastric acid secretion stimulated by 200-ml liquid meals containing 8% peptone. CRF did not affect plasma gastrin concentrations. These results indicate that CRF microinjected into the third cerebral ventricle inhibits gastric acid secretion in conscious dogs. CRF-induced inhibition of gastric acid secretion appears to be mediated by the sympathetic nervous system and, in part, by opiate and vasopressin-dependent mechanisms.
Therapeutic Efficacy of Amantadine HCl and Rimantadine HCl in Naturally Occurring Influenza A2 Respiratory Illness in Man
Authors: W. L. Wingfield, David Pollack, R. R. Grunert
Journal: New England Journal of Medicine (1969)

In a double-blind, placebo-controlled study of the therapeutic efficacy of amantadine HCl (1-adamantanamine HCl) and of rimantadine HCl (μmethyl-1-adamantanemethylamine HCl) in patients with naturally occurring respiratory disease due to influenza A2, carried out at the Virginia State Penitentiary during an influenza A2 outbreak in January, 1968, both drugs were found to be effective therapeutically. Statistically significant increases in the rate of overall clinical improvement, in the rate of defervescence and in the rate of disappearance of signs and symptoms of illness were observed in the patients who received amantadine HCl or rimantadine HCl as compared to those who received placebo.
Twenty years of vocational training in the west of Scotland.
Authors: D R Kelly, T S Murray
Journal: BMJ (1991)

To assess the career paths of doctors who completed vocational training in the west of Scotland between 1968 and 1987 and their views on the hospital component of their training.Retrospective analysis of the experience and opinions of vocationally trained doctors obtained from a postal questionnaire.West of Scotland.1255 Doctors identified from Glasgow University records who had been vocationally trained in the west of Scotland between 1968 and 1987.Personal details; employment; jobs held currently; additional professional commitments; importance of hospital posts held in various specialties to respondents currently in general practice; and retrospective choice of hospital posts, based on subsequent experience.619 Responses were received, 543 initially and 76 after a letter of reminder, from a possible total of 974 (excluding 153 questionnaires returned by the post office and 128 returned because of misunderstanding between the name and address); the overall response rate was therefore 64%. 607/619 (98%) Respondents were employed at the time of the study, of whom 517/607 (85%) were in general practice. A third (202/609) had been unemployed at some point, significantly more of them women (122/243, 50% v 80/376, 21%; chi 2 = 54.8, p less than 0.001). 510/563 (91%) Respondents held one postgraduate qualification or more, and 284/612 (46%) had additional professional commitments. The hospital posts most commonly held were in obstetrics and gynaecology, psychiatry, paediatrics, and medicine. Medicine, obstetrics, paediatrics, and dermatology were considered to be the most relevant hospital specialties by those who had experience of them and were now in general practice. Although ophthalmology and ear, nose, and throat were not rated highly by these doctors, other respondents wished that they had held posts in these specialties (32 and 40 respectively). During the hospital training 354/475 (75%) respondents thought that they were looked on as a junior hospital doctor and not as a trainee for general practice.Most of those who had entered vocational training were in employment, and most were in general practice. According to them, the most beneficial hospital posts for vocational training are medicine, obstetrics, paediatrics, and dermatology. Trainees should be encouraged to attend clinics in gynaecology, ear, nose, and throat, and ophthalmology.
Papules, Plaques, and Nodules in an Immunocompromised Patient
Authors: Xiao-Yong Man, Min Zheng
Journal: JAMA (2012)

AN 85-YEAR-OLD MAN IS ADMITTED FOR EVALUATION OF MULTIPLE PAPULES, plaques, and subcutaneous nodules on his face, trunk, and extremities. The patient has itching. There is no history of trauma. He has an 8-year history of diabetes and Sjogren syndrome with eye and mouth involvement and has been treated with varied doses of oral methylprednisolone for 5 years. During the 3 years prior to admission, he took 12 mg/d of methylprednisolone. Over the last 5 months, he received topical steroids and antifungal agents. Skin examination reveals multiple erythematous papules on his face and eyelids, clustered or solitary reddish or purple papules, indurated shining plaques, and subcutaneous nodules on his wrists (FIGURE 1A), arms, and lower limbs, mainly around the knees (Figure 1B) and thighs. Pus is not expressed with pressure. There are no lesions on his scalp, eyebrow, upper lip, chin, axillae, pubic area, palms, or soles. What Would You Do Next?
Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.
Authors: V Kon, A Yared, I Ichikawa
Journal: Journal of Clinical Investigation (1985)

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.
The first 15: New Zealand doctors and rugby
Authors: S. Srinivasa, Y.-M. Tan, A. Connolly, A. G. Hill
Journal: BMJ (2010)

New Zealanders are passionate about rugby and no professional group is an exception. The medical community in New Zealand has a proud tradition of many individuals playing international rugby and then going on to succeed in their medical career. In anticipation of the impending rugby World Cup, and as a point of historical interest, we conducted a search of medically qualified New Zealanders who played rugby at university, provincial or national level to identify a first 15 as well as reserve players. No database recording players’ occupations is currently maintained, so a systematic search was not possible. We undertook the search with the help of the New Zealand Rugby Museum, the New Zealand Rugby Almanak , representatives from all the provincial rugby unions, and conversations with the knowledgeable individuals acknowledged below. The criteria for selection required that a player must be a medically qualified professional and eligible to play for the New Zealand national team, the All Blacks. Once identified as eligible, players were selected for the team on the basis of their playing abilities and not for their off-field exploits. All Blacks were given preference for each position if more than one candidate was eligible. We identified over 150 potential candidates, the majority of whom had represented their university. Twenty eligible candidates had played for either the All Blacks or the New Zealand Maori team (see box). The first 15 are listed here. #### New Zealand rugby representatives (All Black number)
Quantitative gastroesophageal reflux and pulmonary function in asthmatic children and normal adults receiving placebo, theophylline, and metaproterenol sulfate therapy
Authors: W.E. Berquist, G.S. Rachelefsky, N. Rowshan, S. Siegel, R. Katz, M. Welch
Journal: Journal of Allergy and Clinical Immunology (1984)
Aricept advertisement breached code
Authors: J. Wise
Journal: BMJ (1998)

An advertisement for donepezil (Aricept) breached the advertising code of practice and did not give a balanced view of the data, the Prescription Medicines Code of Practice Authority has ruled.

The advertisement, which was published in the BMJ and other medical journals, was headed “Mum has Alzheimer's,” beneath which was a large coloured photograph of an elderly woman and her daughter, both smiling. Partially superimposed on the top right hand corner of this photograph was a …
Unexplained Syncope Evaluated by Electrophysiologic Studies and Head-up Tilt Testing
Authors: Jasbir S. Sra, Alfred J. Anderson, Shabbir H. Sheikh, Boaz Avitall, Patrick J. Tchou, Paul J. Troup, Carol J. Gilbert, Masood Akhtar, Mohammad R. Jazayeri
Journal: Annals of Internal Medicine (1991)

To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies.Retrospective study.Inpatient services of a tertiary referral center.Eighty-six consecutively referred patients with unexplained syncope.All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing.Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients.The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most patients.
OSTEITIS FIBROSA CYSTICA AND RENAL CALCULI WITHOUT HYPERCALCEMIA
Authors: Clarence L. Robbins
Journal: JAMA (1935)

Recent contributions<sup>1</sup>to the subject of hyperparathyroidism have stressed the necessity to consider the entire clinical and laboratory picture of the disease rather than to place too much reliance on any isolated observation or group of observations. The so-called metabolic criteria of hyperparathyroidism may be duplicated in conditions in which there is no evidence of hyperfunction of the parathyroids.<sup>2</sup>Likewise in proved cases of hyperparathyroidism the metabolic criteria may be absent. Gutman<sup>1</sup>has noted that, of seventy-eight reported cases of hyperparathyroidism in which determinations of serum calcium were recorded, 25 per cent failed to show a consistent hypercalcemia. This case of osteitis fibrosa cystica generalisata is reported as an instance of probable hyperparathyroidism fulfilling all the clinical and roentgenographic criteria of the condition with, nevertheless, consistently normal concentrations of calcium and phosphorus in the serum. Mrs. M. C. was first admitted to the New Haven hospital in 1922, when she
32 CIRCULATING MONOCYTE ENDOTOXIN TOLERANCE IN ACUTE LIVER FAILURE: ROLE OF HEPATICALLY DERIVED IL-10
Authors: C. Antoniades, L. Taams, M. Paris, M.S. Longhi, I. Carey, M. Bruce, G. Auzinger, W. Bernal, W. Jassem, A. Quaglia, H. Nigel, D. Vergani, J. Wendon, M. Thursz
Journal: Journal of Hepatology (2011)
Cell-penetrating Peptides as Versatile Vehicles for Oligonucleotide Delivery
Authors: Helerin Margus, Kärt Padari, Margus Pooga
Journal: Molecular Therapy (2012)

Short regulatory oligonucleotides (ONs) have a great therapeutic potential for the modulation of gene expression due to their high specificity and low toxicity. The major obstacles for in vivo clinical applications of ONs are the poor permeability of plasma membrane to nucleic acids and the sensitivity of ONs to enzymatic degradation. Hence, various delivery vehicles have been developed to ensure the transduction of ONs into cells. Among these, the cell-penetrating peptides (CPPs) have gained quickly broadening popularity as promising nonviral transmembrane delivery vectors. For coupling of nucleic acids to CPPs, two distinct strategies may be applied-covalent and noncovalent. The majority of earlier studies have used covalent coupling of CPPs to ONs. However, the number of studies demonstrating very high therapeutic potential of noncovalent complexes of ONs with novel CPP-based delivery vehicles is explosively increasing. In this review, the recent developments in the application of CPP-mediated oligonucleotide delivery by noncovalent strategy will be discussed.