tbuckley/cabot-search huggingface dataset:
Neuroglia and Pioneer Neurons Express UNC-6 to Provide Global and Local Netrin Cues for Guiding Migrations in C. elegans
Authors: William G Wadsworth, Harshida Bhatt, Edward M Hedgecock
Journal: Neuron (1996)

Netrins are laminin-related proteins that guide circumferential migrations on the ectoderm. To understand how netrin cues direct cell movements, we examined the expression of nematode netrin UNC-6 from embryo to adult. UNC-6 is expressed in 12 types of neuroglia and neurons, creating a hierarchy of netrin cues in the developing nervous system. Comparing gene expression pattern with in vivo phenotypes, we suggest how multiple netrin cues, each with a characteristic role, guide cells and axons during development. We also present the molecular analysis of selective loss-of-function and null alleles. The results indicate that the biological activities of netrins are mediated through distinct protein domains. Subtle mutations in domain VI can produce selective defects in both direction- and tissue-specific guidance. EGF-like module V-2 is essential for dorsal guidance activity; we infer this module is important for interactions between UNC-6 and the dorsal guidance receptor UNC-5.
Left ventricular regional systolic and diastolic function in conscious sheep undergoing ischemic preconditioning
Authors: E Lascano
Journal: Cardiovascular Research (1999)

Late preconditioning diastolic protection and cardiac function optimization by the combined effects of late and early preconditioning have not been studied in conscious animals. This study assessed in fully conscious sheep: (1) whether 24 h after a reversible ischemia, a new ischemic episode results in lesser systo-diastolic dysfunction (late preconditioning protection) and (2) whether the addition of early preconditioning (brief episodes of ischemia-reperfusion before the subsequent sustained ischemia) on the second day of late preconditioning optimized the second window of protection.Three protocols were assessed: (a) late preconditioning, 9 min ischemia and 2 h reperfusion was done on two consecutive days; (b) early plus late preconditioning, as in protocol (a) except that on day 2 the heart underwent three periods of 3 min ischemia-6 min reperfusion prior to the sustained 9 min ischemia; (c) early preconditioning, the same protocol as in (b) except that day 2 was separated 1 week from day 1.Late preconditioning decreased regional radial diastolic stiffness from 147 +/- 26% (day 1) to 96 +/- 14% (day 2), at 2 h of reperfusion (mean +/- SEM, p < 0.05), but did not protect against systolic stunning (thickening fraction and regional stroke work). Early plus late preconditioning did not improve late preconditioning findings. Early preconditioning alone did not protect either systolic or diastolic functions.In conscious sheep, there is diastolic but not systolic mechanical protection with late preconditioning. Diastolic protection is not enhanced by the addition of early preconditioning.
Osteoporosis in men: who should we treat?
Authors: J. Compston
Journal: BMJ (2014)

Protective treatment for men with previous fragility fractures would be a good start

Although osteoporosis is a condition traditionally associated with postmenopausal women, it also causes substantial morbidity and mortality in older men.1 Low rates of diagnosis and treatment in men arise from lack of awareness of the condition and uncertainty about how to identify those who need treatment. Diagnostic criteria for osteoporosis in men based on bone mineral density (BMD) have proved controversial, and consensus is lacking around diagnosis and treatment. In their linked paper (doi:10.1136/bmj.g4120), Ensrud and colleagues explore how the different approaches to diagnosis alter the proportion of older men identified as candidates for treatment.2

The debate around diagnostic criteria for osteoporosis in men hinges on whether reference BMDs from healthy women or men should be used and whether BMD measurements at one site or multiple sites should be considered. Women have lower BMD than men, so a diagnosis based on T scores derived from healthy women requires a lower absolute BMD than one based on T scores derived from healthy men. Furthermore, the less than perfect correlation between BMD measurements at different skeletal sites means that the prevalence of osteoporosis seems to increase with the number of …
Interplay between IFN-γ and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation
Authors: Rachel M. McLoughlin, Janusz Witowski, Rachel L. Robson, Thomas S. Wilkinson, Suzanne M. Hurst, Anwen S. Williams, John D. Williams, Stefan Rose-John, Simon A. Jones, Nicholas Topley
Journal: Journal of Clinical Investigation (2003)

Regulated recruitment and clearance of neutrophils (PMN) is the hallmark of competent host defense and resolution of inflammation. We now report that IFN-γ controls PMN infiltration and modulates IL-6 signaling through its soluble receptor (sIL-6R) to promote their apoptosis and clearance. Induction of peritoneal inflammation in IFN-γ–deficient (IFN-γ–/–) mice emphasized that the initial rate of PMN recruitment was impaired. This defect in PMN recruitment was also associated with the suppressed intraperitoneal expression of IL-1β and IL-6. Reconstitution of IFN-γ signaling restored the rate of PMN infiltration and IL-6 levels and was accompanied by normalization of PMN-activating CXC chemokine expression. To test whether local IL-6 signaling modulated PMN recruitment, inflammation was induced in IFN-γ–/– and IL-6–/– mice and cytokine signaling adapted by intraperitoneal sIL-6R–IL-6 fusion protein (HYPER-IL-6) or IFN-γ. Although HYPER-IL-6 attenuated PMN influx in IFN-γ–/– mice, IFN-γ had no effect on PMN infiltration in IL-6–/– mice. Examination of the leukocyte infiltrate from IFN-γ–/–, IL-6–/–, and wild-type mice showed that apoptosis was aberrant in the absence of IFN-γ and IL-6 as a result of impaired sIL-6R signaling. These data emphasize a pivotal role for IFN-γ in regulating innate immunity through control of both the recruitment and clearance phases of PMN trafficking.
Time for organisational development in healthcare organisations
Authors: C. Koeck
Journal: BMJ (1998)

The discussion on quality of care has come a long way: from the efforts and research of visionaries such as Ernest Codman and Avedis Donabedian in the 1970s to the introduction of quality management and continuous quality improvement; from assessing quality from the perspective of a single profession to a more integrated and process oriented view; from control to improvement. Most of this development has been driven by pioneers with an outstanding vision, such as Don Berwick, who felt that we could do better for our patients and must improve. However, numerous publications, countless conferences, and broad discussions have not yet produced sufficient improvements of actual quality. This week the journal Quality in Health Care adds to this debate with a supplement on Organisational Change: The Key to Quality Improvement that reviews current thinking (and achievements) in the NHS in particular and health care in general (see www.bmj.com or www.qualityhealthcare.com). It provides yet another sign that what has been achieved cannot yet satisfy patients, payers, and professionals. So why is it so hard to get real improvement and change?

Over the past century health care has also come a long way—from the doctor in a solo practice, a generalist able to master all the relevant medical knowledge and apply it to the treatment of his patients, to the network of highly specialised consultants, who depend on each other for complementary expertise; from the asylum, where the interaction of nurses and doctors could guarantee optimal treatment, to today's hospital, where personnel clustered in over a thousand job categories have to run a highly complex and interactive system.1 As …
A rare cause of thunderclap headache
Authors: J. M. Coutinho, J. Stam
Journal: BMJ (2011)

A 44 year old woman presented to the emergency room with a severe headache that had suddenly developed (within seconds) on wakening two days earlier. The headache was diffusely located and radiated to the neck. She was nauseous and had vomited. Several weeks ago she had undergone a colonoscopy because of frequent and bloody diarrhoea and had been diagnosed with ulcerative colitis. She had been receiving mesalazine and prednisolone (40 mg daily) for the past four weeks. She also used a third generation oral contraceptive. Her remaining medical history was unremarkable.

On examination the patient was fully awake. Her blood pressure was 120/90 mm Hg, pulse rate 95 beats/min, and temperature 37°C. She was photophobic and had slight nuchal rigidity. The remaining neurological examination, including fundoscopy, showed no abnormalities. Initial blood tests showed a C reactive protein concentration of 20 mg/l, a white cell count of 11.4×109/l, and a platelet count of 286×109/l. An urgent computed tomography scan of the brain (non-enhanced) showed a hyperdense aspect of the straight sinus, but was otherwise unremarkable. Subarachnoid haemorrhage was excluded as a possible cause.



### 1 Which neurological condition is the most likely diagnosis?

#### Short answer

Cerebral venous thrombosis is the most likely diagnosis.

#### Long answer

A subarachnoid haemorrhage is the foremost …
Investigational treatments: process, payment, and priorities
Authors: K. J. Meador
Journal: JAMA (1997)

To  Editor.  —In his article on investigational treatments, Dr Eddy 1 describes the minimum evidence required to provide physicians and patients with  information they need to determine how  treatment will affect  patient's outcomes. In addition, he asserts that denial of coverage is one of  few barriers that delays  dissemination of procedures, tests, and off-label uses of drugs before their effectiveness can be determined.  Who should make these determinations? Eddy states that  evidence should be sufficient to enable appropriately trained, motivated, and  people to draw conclusions about  magnitude of  effects. The determination of payment (ie, access) for standard treatments or tests that have proven efficacy, much less  determination of investigational status, is frequently in  purview of health insurance and health maintenance companies. These sources can hardly be deemed impartial and, in most states, are free of medicolegal liability for their decisions. In effect
Total Radical-Trapping Antioxidant Parameter in NIDDM Patients
Authors: Antonio Ceriello, Nadia Bortolotti, Edmondo Falleti, Claudio Taboga, Laura Tonutti, Adriana Crescentini, Enrico Motz, Sebastiano Lizzio, Assunta Russo, Ettore Bartoli
Journal: Diabetes Care (1997)

OBJECTIVE The existence of an oxidative stress in diabetes is still debated. This is largely due to the lack of good tools to assay the level of oxidative stress. The use of total radical-trapping antioxidant parameter (TRAP) has recently been proposed to explore the antioxidant property of a plasma sample. TRAP may be either directly measured by a fluorescence-based method (TRAPm) or calculated (TRAPc) by a mathematical formula, taking into account the serum levels of four natural antioxidants: protein-bound SH (thiol) groups, uric acid, vitamin E, and vitamin C. The difference between TRAPm and TRAPc is due to antioxidants, which are still unidentified, and to the possible synergism among the antioxidants. RESEARCH DESIGN AND METHODS In this study, we evaluated malondialdehyde (MDA), TRAPm, TRAPc, protein-bound SH groups, uric acid, vitamin E, and vitamin C in 40 NIDDM patients and 40 matched normal control subjects. RESULTS TRAPm and TRAPc were significantly lower in diabetic patients. A good correlation between TRAPm and TRAPc was found in both NIDDM patients (r = 0.68, P &amp;lt; 0.0001) and control subjects (r = 0.74, P &amp;lt; 0.0001). Protein-bound SH groups and uric acid were significantly lower in diabetic subjects, while MDA and vitamin E level were significantly higher. After correction for serum triglycerides (MDA) and cholesterol (vitamin E), MDA lost significance, while vitamin E did not. Vitamin C was not different in the two groups. CONCLUSIONS These data show decreased TRAP levels in NIDDM patients, suggesting the existence of lower antioxidant defenses in diabetes. The decrease appears to be due to various antioxidants, some of them not yet clearly defined. TRAP may represent a more reliable estimation of serum antioxidant capacity than the measurement of each known antioxidants. The correlation found between TRAPm and TRAPc values suggests that TRAPc, easier to measure than TRAPm, might be adequately reliable for routine assessment of oxidative stress in diabetic patients.
Chromosomes and Transformation of Lymphocytes in Lymphoproliferative Disorders
Authors: S. D. Lawler, C. R. Pentycross, B. R. Reeves
Journal: BMJ (1968)

In chronic lymphocytic leukaemia the majority of circulating lymphocytes which responded to phytohaemagglutinin in vitro were found to have normal karyotypes. A minor population of cells in patients treated with chemotherapy had an increased number of chromosomal rearrangements as compared with cells from normal controls and untreated patients with chronic lymphocytic leukaemia. Probably bonemarrow and lymph-node cells also had a normal karyotype. In the other lymphoproliferative disorders the peripheral blood lymphocytes had either normal karyotypes or chromosomal abnormalities attributable to treatment, even in those cases where the tumour cells of involved lymph nodes were known to have abnormal karyotypes. It was possible that circulating tumour cells were present in one case.
Macroscopic Evaluation of Rectal Cancer Resection Specimen: Clinical Significance of the Pathologist in Quality Control
Authors: Iris D. Nagtegaal, Cornelis J.H. van de Velde, Erik van der Worp, Ellen Kapiteijn, Phil Quirke, J. Han J.M. van Krieken
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Quality assessment and assurance are important issues in modern health care. For the evaluation of surgical procedures, there are indirect parameters such as complication, recurrence, and survival rates. These parameters are of limited value for the individual surgeon, and there is an obvious need for direct parameters. We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a randomized trial for rectal cancer. PATIENTS AND METHODS: The pathology reports of all patients entered onto a Dutch multicenter randomized trial were reviewed. All participating pathologists had been instructed by workshops and videos in order to obtain standardized pathology work-up. A three-tiered classification was applied to assess completeness of the total mesorectal excision (TME). Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment. RESULTS: Included were 180 patients. In 24% (n = 43), the mesorectum was incomplete. Patients in this group had an increased risk for local and distant recurrence, 36.1% v 20.3% recurrence in the group with a complete mesorectum (P = .02). Follow-up is too short to observe an effect on survival rates. CONCLUSION: A patient’s prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen. We conclude that pathologists are able to judge the quality of TME for rectal cancer. With this direct interdisciplinary assessment instrument, we establish a new role of the pathologist in quality control.
Moral Medicine and Universal Health Care
Authors: Irvin Emanuel
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The Editorial<sup>1</sup>"Crisis, Ethics, and the American Medical Association: 1947 and 1997" was important and timely. However, I do not believe that "[t]he main challenge facing medicine today is to ensure that free-market medicine remains moral medicine." On the contrary, I believe that the main challenge of American medicine is to use its influence to promote the development of a universal health care system in this country. "Moral medicine" is more easily assured in a universal system. That the medical establishment has missed every window of opportunity over the past half century to foster its development is probably one reason for the crisis in free-market medicine. Conditions in the United States stand in stark contrast to those in Taiwan, which has a universal health insurance system, described in the same issue.<sup>2</sup>Taiwan was a third-world country 3 decades ago and now has a successful industrial
High incidence of hypoglycaemia in African patients treated with intravenous quinine for severe malaria.
Authors: W Okitolonda, C Delacollette, M Malengreau, J C Henquin
Journal: BMJ (1987)

Changes in plasma glucose and insulin concentrations were monitored over 24 hours in 28 African patients receiving quinine intravenously in an average dose of 8.5 mg base/kg over one hour eight hourly for severe malaria. The patients (nine children and 19 adults) were moderately undernourished; none was pregnant or had renal insufficiency. Plasma insulin concentrations rose during the infusion and then declined. Plasma glucose concentrations were decreased at two, three, and four hours after the start of the infusion. Insulin: glucose ratios were raised between half an hour and two hours after the start of the infusion. The three infusions of quinine increased plasma insulin concentrations in a similar way. In nine patients, including four children, plasma glucose concentrations fell below 2.8 mmol/l on one or two occasions. At the time of the hypoglycaemia plasma insulin concentrations were inappropriately high as shown by a consistent and often considerable increase in the insulin:glucose ratio. Hypoglycaemia that may pass unnoticed in comatose patients is thus a common complication of treating severe malaria with quinine, in particular in children. Its high incidence calls for attentive monitoring and preventive measures.
A NEW OPERATION TABLE, DESIGNED TO AVOID ALL LIFTING OF THE PATIENT
Authors: John Cooke Hirst
Journal: JAMA (1923)

One of the great faults in technic of all operating rooms has been the necessity of lifting a patient from the bed to the ward carriage, thence to the operating table, thence back to the carriage, and back to bed again. This involves an entirely needless amount of work and energy on the part of the operating room personnel, and, besides, is deleterious to both the patient and the nurses, on whom most of the burden falls. It is always desirable to avoid unnecessary disturbance of the patient before and after any operation, but especially after such operations as bone plating, fracture, upper abdominal surgery, and any operation requiring drainage. All this cumbersome method of repeated lifting is necessitated by every form of operating table in use today. These methods have in no way changed since the beginning of operating room technic, and we felt that such medieval methods should
Licit steroid use--hope for the future.
Authors: A P Millar
Journal: British Journal of Sports Medicine (1994)

Anabolic steroid use has escalated in recent years along with law enforcement. A total of 169 athletes participated in a trial of medical prescription designed to minimize harm as drug elimination is impossible. This showed one-third of athletes achieved their goal in one course, and few were frequent users over the 3-to-5-year period of the trial. Side effects were minimal and reversible.
Inquiry finds brains were removed without consent
Authors: S. Mayor
Journal: BMJ (2003)

The UK government is planning a new human tissue bill for England in response to a report published this week that stated that thousands of brains had been removed during postmortem examinations over the past 30 years without prior family consent and kept for mental health research.

   ![][1] 

Many doctors did not realise that they were breaking the law by failing to seek the consent of relatives for the retention of brains for research 

GEOFF TOMPKINSON/SPL

The inquiry, led by Her Majesty's Inspector of Anatomy, Dr Jeremy Metters, was prompted by …

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Testicular Cancer, Clinical Stage I
Authors: John P. Donohue
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 March 1989Testicular Cancer, Clinical Stage IJohn P. Donohue, MDJohn P. Donohue, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-5-409_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Stephens and Williamson (1) reviewed seven surveillance series and cited these experiences as a mandate for abandonment of surgical staging of testicular cancer, clinical stage I. The authors reviewed the literature and did not report their own experience. From my experience in a single series of more than 1000 cases that occurred over a 20-year period, I have found that testis tumor is still treacherous and is perhaps best staged early and accurately. If such staging can be done without any long-term morbidity, it is both prudent and rational to do so, at least for the time...References1. StephensWilliamson RS. Clinical stage I testicular cancer: orchiectomy without node dissection [Editorial]. Ann Intern Med. 1988;109:179-81. LinkGoogle Scholar2. Freedman L. Histopathology in the prediction of relapse of patients with stage I testicular teratoma treated by orchidectomy alone. Lancet. 1987;2:294-7. CrossrefMedlineGoogle Scholar3. Donohue J. Preservation of ejaculation following nerve sparing retroperitoneal lymphadenectomy (RPLND). J Urol. 1988;139:206A. Google Scholar4. Drasga R. Fertility after chemotherapy for testis cancer. J Clin Oncol. 1983;1:179-83. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indiana University Medical Center Indianapolis, IN 46223 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRetroperitoneal imaging with third and fourth generation computed axial tomography in clinical stage I nonseminomatous germ cell tumorsStaging Relationships and Outcome in Early Stage Testicular Cancer: A Report From the Testicular Cancer Intergroup StudyThe evolving role for surgery in the management of nonseminomatous testicular carcinoma 1 March 1989Volume 110, Issue 5Page: 409-410KeywordsMorbidityTesticular cancer Issue Published: 1 March 1989 PDF DownloadLoading ...
Insulin-like Growth Factor and Apolipoprotein B
Authors: Richard E. Ostlund
Journal: JAMA (1991)

<h3>To the Editor.</h3> —Apolipoprotein B (apo B) is the principal protein component of the atherogenic lipoproteins low-density (LDL) and very-low-density (VLDL). The factors that regulate plasma apo B levels are of particular interest since in some data apo B is more closely related to coronary heart disease than LDL or VLDL cholesterol.<sup>1</sup>We wondered whether insulin-like growth factor I (IGF-I) might be such a factor since the infusion of recombinant IGF-I recently was reported to lower plasma cholesterol levels.<sup>2-4</sup>Indeed, previous work had shown that IGF-I deficiency states were accompanied by hypercholesterolemia.<sup>5-7</sup>Our hypothesis was that apo B—containing lipoproteins were inversely related to circulating IGF-I in normal subjects. Insulin-like growth factor I,<sup>8</sup>insulin-like growth factor II (IGF-II),<sup>9</sup>and apo B<sup>10</sup>were measured in serum frozen at —70° obtained from 148 well-characterized, healthy men and women between the ages of 60 and 70 years for