tbuckley/cabot-search huggingface dataset:
Clinical Cardiology and Diabetes, vol 3, part 1: Clinical Manifestations, Medical Management; part 2: Surgical Management, Renal Disease, Special Problems
Authors: Mark E. Molitch
Journal: JAMA (1981)

These two books are part of a larger series that also includes volume 1, part 1:<i>Fundamental Considerations in Cardiology and Diabetes;</i>part 2:<i>Diagnostic Procedures</i>and volume 2,<i>Clinical Pharmacology and Use of Selected Cardiac Drugs</i>. As such, this collected set of works on a specifically defined subject should be definitive and comprehensive. Unfortunately, this is not true, at least for the two books being reviewed here. Both books also suffer from significant delays in publishing, which limit their usefulness in 1981. Part 1 is very uneven and suffers from poor editorial direction in that diabetes and cardiology are poorly integrated. Chapters 1 and 4 deal with diet and insulin therapy and do not address the problems of the patient with heart disease in any detail. Two chapters deal with oral hypoglycemic agents; one is a pro-University Group Diabetes Program summary by one of its participants, who extrapolates the
Factor II antigen in liver disease and warfarin‐induced vitamin K deficiency: Correlation with coagulant activity using echis venom
Authors: James J. Corrigan, David L. Earnest
Journal: American Journal of Hematology (1980)

Abstract Four coagulation factors (II, VII, IX, X) are synthesized in the liver as precursor forms. Vitamin K is necessary for their conversion to functional factors. Factor II precursor is antigenically similar to factor II and can be activated to form thrombin by Echis carinatus venom. Forty‐one patients with liver disease and 30 patients with vitamin K deficiency (Warfarin treated), were compared with 51 normal patients. Rats with CCl 4 ‐induced hepatic necrosis and animals given Warfarin were also studied. The following measurements were made: standard prothrombin time; Echis clotting time; factor II coagulant assay with thromboplastin; factor II assay with Echis venom; and factor II antigen (human) by electroimmunoassay. In animals and humans with liver disease, factor II was reduced, as measured by all techniques. With vitamin K deficiency functional factor II was reduced, but factor II antigen and Echis factor II activity were normal. The data suggest that the prothrombin time and Echis coagulation methods can be used to differentiate whether the coagulopathy in liver disease is due to reduced precursor levels of factor II, vitamin K deficiency (ie, impaired formation of functional from precursor factor II), or both.
Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem
Authors: Daniel A. Peterson
Journal: Journal of Clinical Investigation (2004)

Degeneration of brain tissue following stroke leads to functional impairment with limited brain self-repair. New evidence suggests that delivery of circulating CD34(+) human umbilical cord blood cells can produce functional recovery in an animal stroke model with concurrent angiogenesis and neurogenesis leading to some restoration of cortical tissue. While some alternative interpretations of this data are offered herein, the study provides encouraging evidence of functional recovery from stroke in an animal model using stem cell therapy.
Drug sales in four European countries still differ
Authors: S. Garattini
Journal: BMJ (2003)

EDITOR—The box shows, by value, the top selling pharmaceutical products that are common to Italy, France, Germany, and the United Kingdom. In 1992,1 1996,2 and 2001 few products were prescribed in all four countries. Nineteen active substances were common to three countries, 17 to two countries, and 63 were on only one country's list.

Several classes of drugs were represented in all four countries but with different products. For example, angiotensin converting enzyme inhibitors were prescribed …
Reperfusion injury, antioxidants and hemodynamics during orthotopic liver transplantation
Authors: Helen F. Goode, Nigel R. Webster, Peter D. Howdle, Jack P. Leek, J. P. A. Lodge, Sammi A. Sadek, Barry E. Walker
Journal: Hepatology (1994)

Endothelial injury occurs as a result of oxygen free radical production after ischemia and reperfusion of transplanted livers, causing hemodynamic disturbance. Patients with chronic liver disease generally have low levels of fat-soluble vitamins, which have important antioxidant roles. We therefore assessed circulating levels of the antioxidants vitamin A, vitamin E, beta-carotene and lycopene, indices of lipid peroxidation and hemodynamic changes during elective orthotopic liver transplantation in 12 patients. We found that initial antioxidant levels were severely depleted compared with healthy subjects, and in some patients carotene and lycopene levels were undetectable. Increased lipid peroxidation was also evident, as shown by thiobarbituric acid-reactive substances. On reperfusion of the liver graft, vitamin A and E levels fell (p < 0.01) and were associated with decreases in systemic vascular resistance (p < 0.02). These data show that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.
Tc-99m MDP Uptake by Metastatic Chondrosarcoma in the Lung
Authors: SERGEY MEKHMANDAROV, SANTIAGO ENGELBERG, DVORA NASS, SARA APTER, LIONEL LIEBERMAN
Journal: Clinical Nuclear Medicine (1989)

A variety of primary and secondary malignancies may accumulate bone-seeking agents. We present a patient with metastatic chondrosarcoma to the lung that was shown to concentrate avidly Tc-99m MDP. To the best of the authors' knowledge, Tc-99m MDP uptake in metastatic chondrosarcoma of the lung has not been described previously.
darwin's legacy and the evolution of cerebral asymmetries
Authors: onur güntürkün
Journal: Behavioral and Brain Sciences (2005)

vallortigara &amp; rogers (v&amp;r) assume that the alignment of escape responses in gregarious species is the central evolutionary organizer of a wide range of cerebral asymmetries. although it is indeed likely that the benefits of a population asymmetry in social species outweigh its costs, it is hard to see (a) why the population should not oscillate between two subgroups with mirror-image asymmetries, (b) why solitary animals should keep their inherited population asymmetry despite a resulting fitness reduction, and (c) and why so many vertebrate species have comparable cerebral asymmetries.
Hereditary Tyrosinemia and the Heme Biosynthetic Pathway. PROFOUND INHIBITION OF δ-AMINOLEVULINIC ACID DEHYDRATASE ACTIVITY BY SUCCINYLACETONE
Authors: Shigeru Sassa, Attallah Kappas
Journal: Journal of Clinical Investigation (1983)

Succinylacetone (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumarylacetoacetate hydrolase. It is known that patients with this hereditary disease excrete excessive amounts of delta-aminolevulinic acid (ALA) in urine and that certain patients have an accompanying clinical syndrome resembling that of acute intermittent porphyria (AIP). In order to elucidate the relation of succinylacetone to the heme biosynthetic pathway, we have examined the effects of this metabolite on the cellular heme content of cultured avian hepatocytes and on the activity of purified ALA dehydratase from normal human erythrocytes and from mouse and bovine liver. Our data indicate that succinylacetone is an extremely potent competitive inhibitor of ALA dehydratase in human as well as in animal tissues. By using purified preparations of the enzyme from human erythrocytes and mouse and bovine liver, an inhibitor constant ranging from 2 x 10(-7) M to 3 x 10(-7) M was obtained. In cultured hepatocytes, succinylacetone also inhibited ALA dehydratase activity, decreased the cellular content of heme and cytochrome P-450, and greatly potentiated the induction response of ALA synthase to drugs such as phenobarbital, chemicals such as allylisopropylacetamide and 3,5-dicarbethoxy-1,4-dihydrocollidine, and natural steroids such as etiocholanolone. Four patients with hereditary tyrosinemia have been studied and all were found to have greatly depressed levels of erythrocyte ALA dehydratase activity and elevated concentrations of this inhibitor in urine. These findings indicate that tyrosinemia is a disorder of special pharmacogenetic interest because succinylacetone, an abnormal product of the tyrosine metabolic pathway, resulting from the primary gene defect of the disease, profoundly inhibits heme biosynthesis in normal cells through a blockade at the ALA dehydratase level, leading to clinical and metabolic consequences that mimic another genetic disease, AIP.
Abstract P4-03-01: Analysis of the impact of intraoperative margin assessment with adjunctive use of MARGINPROBE® vs. standard of care on margin status with different definitions of positive margin depth, results from a randomized prospective multi center study
Authors: M Gittelman
Journal: Cancer Research (2013)

Abstract Background: The current practice of breast conserving surgery (BCS) involves intraoperative margin assessment according to the surgeon's gross assessment and judgment. This intraoperative assessment has been associated with a 20% to 40% reoperation rate to assure negative margins. MarginProbe (Dune Medical Devices, MA, USA) was developed to provide real-time assessment of lumpectomy specimens to evaluate for the presence of disease at the surgical margins. A 21-center international pivotal study was conducted to determine if adjunctive use of MarginProbe can enable surgeons to identify positive margins intraoperatively, resulting in fewer patients who are candidates for re-excision procedures. Results for a 1mm definition of positive margins have been reported previously. We sought to understand the benefit of device use at alternative thresholds. Methods: 664 women with non-palpable lesions undergoing lumpectomy for DCIS and invasive cancer were enrolled and 596 randomized (1:1) in the operating room following standard of care (SOC) lumpectomy. In the device arm, MARGINPROBE was used to assess all surfaces of the lumpectomy specimen and positive readings required additional resections. The device was not used on additional resections. All specimens were examined to verify excision of the target lesion intraoperatively. Pathologists were blinded to study arm. Additional surgeries to re-excise involved margins were performed per each individual site criteria. Patients were followed for 2 months following surgery; additional procedures were documented. Distance from tumor to each margin face was recorded for each patient. Results: Following lumpectomy, the number of patients having positive margins due to failed intraoperative assessment was significantly reduced in the device arm at each potential definition of positive margins. Patients with positive margins after 1st surgeryDepthDevice (%) N = 298Control (%) N = 298p-value0mm6.413.40.00571mm15.438.3&amp;lt;0.00012mm22.549.7&amp;lt;0.00013mm30.957.0&amp;lt;0.00014mm36.661.7&amp;lt;0.00015mm39.966.4&amp;lt;0.0001*excludes positive margins on shavings, as device was only used on the main specimen Conclusions: It has been shown previously that adjunctive use of MARGINPROBE significantly reduced the number of candidates for re-excision at a 1mm definition of positive margins. Based on this analysis, surgeons can expect a substantial reduction in the number of patients with positive margins at definitions from tumor on ink to 5mm. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-03-01.
Why the Assisted Dying Bill should become law in England and Wales
Authors: T. Delamothe, R. Snow, F. Godlee
Journal: BMJ (2014)

It’s the right thing to do, and most people want it

Lord Falconer’s Assisted Dying Bill is expected to receive its second reading in the House of Lords this month. The BMJ hopes that this bill will eventually become law.

The bill would allow adults who are expected to live six months or less to be provided with assistance to end their lives.1 Two doctors must be satisfied that the person is terminally ill, has the capacity to make the decision to end his or her life, and has a clear and settled intention to do so. This decision must have been reached voluntarily, on an informed basis, and without coercion or duress. Both doctors must be satisfied that the person has been fully informed of the palliative, hospice, and other available care options.

Once both doctors have countersigned the declaration that the person wants to end his or her life, the attending doctor can prescribe the life ending medication, which would be dispensed only after a “cooling off” period of 14 days (or six days if prognosis is less than a month). The person would administer the medication themselves. This is what differentiates …
Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. Evidence that insulin increases glucose uptake merely by providing additional transport sites.
Authors: I Gottesman, L Mandarino, C Verdonk, R Rizza, J Gerich
Journal: Journal of Clinical Investigation (1982)

The present studies were undertaken to assess the mechanism by which insulin increases glucose uptake in man. Because glucose uptake in most mammalian tissues occurs predominantly by a facilitated transport system that follows Michaelis-Menten kinetics, glucose uptake was measured isotopically in normal volunteers over the physiologic range of plasma glucose and insulin concentrations and was subjected to Lineweaver-Burk and Eadie-Hofstee analysis. With both methods, increases in plasma insulin from 18 microunits/ml to 80 and 150 microunits/ml were found to increase the maximum velocity (Vmax) for glucose uptake nearly three- and fivefold, respectively, (P less than 0.025 and P less than 0.001) without significantly altering the Michaelis constant (Km). Because an increase in the affinity or molecular activity of transport sites or provision of additional transport sites that differed from those present basally should have altered the Km, whereas a mere increase in the number of transport sites would have only increased the Vmax, our results indicate that in man, insulin may increase glucose uptake merely by providing additional transport sites.
Pronunciation of Dr Georges Guillain's Name
Authors: Joseph B. Rogoff
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The mispronunciation of Dr Georges Guillain's name by English-speaking physicians has bothered me for many years. Even the medical dictionaries (eg,<i>Dorland's</i>) give the pronunciation as "ge-yan," which is incorrect. This pronunciation is based on a misconception that all<i>ill</i>sounds in French are "liquid." Prominent exceptions are<i>mille, ville</i>, tranquil, and their derivatives (eg, million, village). In all these cases, the sound is the hard L (similar, but not exactly the same, as in English). Furthermore, proper names, as in almost all languages, do not follow any rule (eg, the English name Chaulmundely, which is pronounced "Chumly," or St John, pronounced "Sinjin"). I was Dr Guillain's extern in 1939, and I never heard him called anything but "ghee-lain" (with the final<i>ain</i>nasalized). If Guillain wanted his name pronounced thus, why should we insist on changing it?
Mutagen formation in a model beef supernatant fraction. IV. Properties of the system.
Authors: R T Taylor, E Fultz, M Knize
Journal: Environmental Health Perspectives (1986)

To identify the precursors and elucidate the reaction conditions that yield heterocyclic amine mutagens in cooked meat products and fish, we have used a supernatant 2 (S2) fraction prepared from H2O-homogenized lean round steak. Compounds (MW less than 500) in S2 are the sources of the microsomal-dependent, Salmonella TA 1538 mutagenic activity in open boiled (aqueous), 200 degrees C pressure-heated (aqueous), or 200 to 300 degrees C oven-baked (freeze-dried) homogenates. Combined incorporation-HPLC experiments show that they are also the precursors for frameshift mutagen formation in the outer surfaces of 200 degrees C griddle-fried ground beef. Maximal stimulations of boiled S2 mutagenic activity are given by 10 mM Trp, 2.5 mM creatine phosphate (CP), and synergistically by 10 mM Trp + 2.5 mM CP + 1.0 mM FeSO4 (a mixture abbreviated as S2*). Boiling S2 for 30 hr at the acidic optimum pH of 4.0----600 TA 1538 revertants (no additions) and 1,400 revertants (+CP), while S2*----24,000 revertants/10(8) bacteria/g of dry beef. By the criteria of HPLC, paper electrophoresis, and resistance of the active HPLC fractions to acid-nitrite inactivation, boiled S2 contains 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and a minor amount of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). Boiling S2 with CP doubles the IQ, halves the Trp-P-2, produced traces of MeIQ, and generates an unknown nitrite-resistant mutagen. Boiled S2* contains these same four mutagens, but both the IQ and Trp-P-2 are increased and large amounts of Trp-P-1 also are generated. The identities of IQ, Trp-P-2, and Trp-P-1 were verified by purification and by light-absorption and mass spectra. Their increments in stimulated S2 indicate that Trp (or its degradation products) and CP (or its degradation products) are the beef juice precursors for the indole ring in Trp-P type mutagens and the NH2-imidazole ring in IQ-type mutagens, respectively. Aqueous (pressure) heating or oven-baking S2 for 2 hr at 200 degrees C greatly elevates its TA 1538 activity----45,000 revertants/10(8) bacteria/g of dry beef; dry heating at 300 degrees C----approximately 180,000 revertants/g of dry beef. Along with the increases in total TA 1538 activity at 200 to 300 degrees C, the number of mutagens formed from the less than 500 MW S2 precursors also multiplies.(ABSTRACT TRUNCATED AT 400 WORDS)
Cross Talk between Apoptosis and Invasion Signaling in Cancer Cells through Caspase-3 Activation
Authors: Mutsuko Mukai, Toshiyuki Kusama, Yukou Hamanaka, Takumi Koga, Hiroko Endo, Masaharu Tatsuta, Masahiro Inoue
Journal: Cancer Research (2005)

In solid tumors, cancer cells are exposed to various microenvironmental stresses such as hypoxia, nutritional depletion, and low pH. Cancer cells adapt to these stresses and circumvent cell death. When the antiapoptotic signals overcome the stress, cancer cells might acquire physiologic functions, such as invasiveness, instead of cell death. Here, we report that tumor cells acquire an invasive capacity from apoptotic signals through caspase activation. We treated rat ascites hepatoma MM1 cells with an apoptosis-inducing drug, etoposide, or hypoxia, and assessed the invasion capacity with an in vitro bioassay. Although MM1 cells hardly showed invasiveness in serum-free medium, under stress conditions, invasive capacity accompanied with morphologic change was induced with caspase-3 activation. Such stress-induced invasion as well as morphologic change was suppressed by blocking caspase-3 activity with caspase inhibitors or by RNA interference of caspase-3. In contrast, lysophosphatidic acid-induced invasiveness was not affected by caspase-3 inhibition. These results suggest that caspase-3 activation contributes to the stress-induced invasive capacity of these cancer cells.
Radiotherapy After Definitive Surgery for Breast Cancer
Authors: Seymour H. Levitt
Journal: JAMA (1977)

(1) Radiotherapy after definitive surgery for breast cancer has not been proved to have a deleterious effect on patient survival. (2) The beneficial effect of radiation therapy is to decrease significantly local recurrences (P less than .001), which are very difficult to control once they develop. (3) In the hands of experienced radiotherapists, the incidence of complications is quite low. (4) Adjuvant chemotherapy effects on the prevention of local recurrence are most encouraging but still experimental and should at this stage be used mainly in study situations. (5) Until more detailed information is obtained, radiation therapy remains the most effective, least toxic method for the control of local disease.
Preservation and function of heterologous aortic valves: An Experimental Study
Authors: A. J. Gunning, J. B. Meade
Journal: Thorax (1971)

Heterologous aortic valves are used in many clinics as replacements for diseased human aortic and mitral valves. These valves possess all the advantages of homologous aortic valves and are more easily available to the surgeon. The heterologous valve also provides a greater choice of valve size than does the homograft; this can be of importance when replacing the mitral valve. Heterograft valves, like homografts, are usually preserved for periods ranging from a few days to a few months before insertion into a patient. Four methods of preservation, described, are currently in use. This study compares the effects of these four methods of preservation when pig valves are transplanted into the dog9s aorta.
Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.
Authors: G J Draper, C A Stiller, R A Cartwright, A W Craft, T J Vincent
Journal: BMJ (1993)

OBJECTIVE--To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN--Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING--England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS--All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES--Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS--Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin9s disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS--During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.
Editorial is judgment in advance of the facts
Authors: N. Finer
Journal: BMJ (2010)

Williams’s negative, even nihilistic, approach to obesity treatment and to sibutramine in particular is ill judged and inaccurate.1 His editorial seems to be based mainly on the limited data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT) released by the European Medicines Agency, and perhaps data not in the public domain. It would have been better to await full details of the trial findings before writing an editorial.

To say …