tbuckley/cabot-search huggingface dataset:
Chemotherapy for Hormone-Refractory Prostate Cancer: Now It's a Question of “When?”
Authors: Charles J. Ryan, Mario Eisenberger
Journal: Journal of Clinical Oncology (2005)

Recently, data from two randomized phase III studies that compared docetaxel-based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with docetaxel can prolong life in a significant way for patients with hormone-refractory prostate cancer. For many patients who experience disease progression after androgen-deprivation therapy, however, chemotherapy may not be immediately indicated. Such cases include those individuals with hormone-refractory disease in the absence of clinical metastases, and those with asymptomatic metastatic disease, for example. As a result, clinicians treating patients with hormone-refractory disease must weigh the benefits of earlier chemotherapy against its risks, and may consider other therapies such as secondary hormonal approaches before initiating chemotherapy. This decision is further complicated by the fact that a phase III study designed to compare secondary hormonal therapy with chemotherapy has failed due to lack of accrual. Furthermore, the limitations of chemotherapy for prostate cancer are being clarified and include a lack of standard second-line therapy as well as uncertain benefits for those with nonmetastatic disease. In this review, we will highlight some of the issues that impact on the decision of when to start chemotherapy and in whom as well as the potential benefits of secondary hormonal approaches.
1,3-Butadiene: linking metabolism, dosimetry, and mutation induction.
Authors: J A Bond, G A Csanady, M L Gargas, F P Guengerich, T Leavens, M A Medinsky, L Recio
Journal: Environmental Health Perspectives (1994)

There is increasing concern for the potential adverse health effects of human exposures to chemical mixtures. To better understand the complex interactions of chemicals within a mixture, it is essential to develop a research strategy which provides the basis for extrapolating data from single chemicals to their behavior within the chemical mixture. 1,3-Butadiene (BD) represents an interesting case study in which new data are emerging that are critical for understanding interspecies differences in carcinogenic/genotoxic response to BD. Knowledge regarding mechanisms of BD-induced carcinogenicity provides the basis for assessing the potential effects of mixtures containing BD. BD is a multisite carcinogen in B6C3F1 mice and Sprague-Dawley rats. Mice exhibit high sensitivity relative to the rat to BD-induced tumorigenesis. Since it is likely that BD requires metabolic activation to mutagenic reactive epoxides that ultimately play a role in carcinogenicity of the chemical, a quantitative understanding of the balance of activation and inactivation is essential for improving our understanding and assessment of human risk following exposure to BD and chemical mixtures containing BD. Transgenic mice exposed to 625 ppm BD for 6 hr/day for 5 days exhibited significant mutagenicity in the lung, a target organ for the carcinogenic effect of BD in mice. In vitro studies designed to assess interspecies differences in the activation of BD and inactivation of BD epoxides reveal that significant differences exist among mice, rats, and humans. In general, the overall activation/detoxication ratio for BD metabolism was approximately 10-fold higher in mice compared to rats or humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV
Authors: Camilla S. Graham, Michael Curry, Qi He, Nezam Afdhal, David Nunes, Catherine Fleming, Robert Horsburgh, Donald Craven, Kenneth E. Sherman, Margaret James Koziel
Journal: Hepatology (2004)

Persons with human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-γ or TNF-α in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion , subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression. (Hepatology 2004;40:125-132.)
Serum Alkaline Phosphatase in Pregnancy: an Immunological Study
Authors: D. J. Birkett, J. Done, F. C. Neale, S. Posen
Journal: BMJ (1966)

Cancer of Cervix-Iversen et al.MEDIBAL JOURNAI cm.) from the external cervical os, under direct vision; and under maximum pressure the liquid was sprayed on to the squamo-columnar junction.The liquid was then aspirated from the posterior fornix, and this procedure was repeated three times.The washing (5-6 ml.) was filtered through coarse gauze to remove debris and mucus, and about 0.1 ml. of the filtrate was spread on a slide, air-dried, fixed in methanol, and stained with Papanicolaou stain.The remainder of the filtrate was diluted with 0.85 % saline to give a cell count suitable for the counter.The size-distribution patterns were determined by means of the Coulter counter model B with automatic plotter.The performance of this equipment was regularly checked with a double pulse generator and by repeated use of test particles from the same batch.The Coulter counter and plotter have been described in detail (Kubitschek, 1960 ;Brecher, Jakobek, Schneiderman, Williams, and Schmidt, 1962).The cervical washings were obtained from patients attending gynaecological and post-natal clinics and from patients admitted to the Royal Beatson Memorial Hospital for radiation treatment.Smears and biopsy specimens were examined by the pathological departments concerned, and one of (S.I.) examined the slides from the washings. ResultsThe results of the non-cancer cases are summarized in Table I, and those of the cancer cases in Table II.Some of the latter were examined on two occasions with an interval of one week between washings, and one case on three occasions.
Contralateral Cerebellar Activation in Frontal Lobe Epilepsy Detected by Ictal Tc-99m HMPAO Brain SPECT
Authors: HIKARU SETO, MASASHI SUIMIZU, NAOTO WATANABE, YIWEI WU, MASANARI KAGEYAMA, YUICHI KAMISAKI, MAKOTO MORIJIRI, YASUHIRO TONOYA, MASAYOSHI KURACHI
Journal: Clinical Nuclear Medicine (1997)

A 65-year-old woman with Alzheimer dementia type with status epilepticus had an electroencephalogram, which showed an epileptic focus in the right frontal area. MRI showed no pathologic findings except for mild brain atrophy. Tc-99m HMPAO brain SPECT imaging during the ictal phase showed a marked increase of regional cerebral blood flow in the right dorsolateral frontal lobe, and ipsilateral basal ganglia and thalamus, in which regional cerebral blood flow was increased by 23-83% as compared with the left side. Interestingly, contralateral cerebellar activation was observed, where regional cerebral blood flow was increased by 23% as compared with the right side.
Molecular dosimetry of aromatic amines in human populations.
Authors: P L Skipper, S R Tannenbaum
Journal: Environmental Health Perspectives (1994)

Certain aromatic amines carcinogenic for the human urinary bladder, such as 4-aminobiphenyl, undergo hepatic metabolic activation to N-hydroxylamines, which are transported to the bladder. During the transport process, these reactive species come in contact with hemoglobin and react with this blood protein. The principal hemoglobin adduct formed is a cysteine sulfinamide, and quantitative methods have been developed for the analysis of sulfinamide adducts at the levels present in ordinary human blood specimens. N-acetylation is an alternative metabolic fate to N-hydroxylation. The amount of hemoglobin adduct is decreased to the extent that this pathway is increased relative to N-hydroxylation. Thus, the hemoglobin adduct is sensitive to dose, cytochrome P-450-mediated activation, and N-acetyltransferase-mediated detoxification. In addition, it has been shown that DNA adduct concentration of 4-aminobiphenyl present in human bladder epithelial cells is significantly associated with hemoglobin adduct levels. Thus, the hemoglobin adduct of 4-aminobiphenyl, and perhaps several other aromatic amines, is a good dosimeter for the target tissue dose of the ultimate carcinogenic metabolite of these amines. Several studies have been undertaken in which the hemoglobin adducts of aminobiphenyls in human blood specimens were determined quantitatively. Information concerning exposure status and acetylator phenotype of the same individuals was obtained simultaneously. The results of these studies indicate that the hemoglobin adduct of 4-aminobiphenyl is closely associated with three major risk factors for bladder cancer: cigarette smoking, type of tobacco smoked, and acetylator phenotype. They also support a major etiologic role for aromatic amines in much of human bladder cancer.
Doctors treating their families
Authors: D. Kamerow
Journal: BMJ (2014)

Common, often harmless, sometimes dangerous and wrong



It began for me when I was a boy in the 1950s. My sisters and I would troop over to the house next door where our uncle, a general internist, jabbed us with the Salk polio vaccine. He wasn’t our regular doctor—we had a pediatrician whom we saw regularly for checkups and ear infections—but we sometimes got our injections from him. In retrospect, I’m not sure why we went there for the shots: Convenience? Vaccine scarcity in the early days of polio immunizations? Low (no) cost?

It continued throughout my childhood. Even though he did not regularly see children, our doctor next door was often where we went for acute illnesses. I remember him treating an ingrown toenail, diagnosing chickenpox, and injecting antibiotics for what was likely cellulitis.

It continues today. I am often consulted by family for medical advice and even care, despite the fact that I am a non-practicing family doctor who only teaches part time. How should I respond?

Medical authorities provide some guidance. The American Medical Association says that …
Biotechnology and the New Right: Neoconservatism's Red Menace
Authors: Jonathan D. Moreno, Sam Berger
Journal: The American Journal of Bioethics (2007)

Although the neoconservative movement has come to dominate American conservatism, this movement has its origins in the old Marxist Left. Communists in their younger days, as the founders of neoconservatism, inverted Marxist doctrine by arguing that moral values and not economic forces were the primary movers of history. Yet the neoconservative critique of biotechnology still borrows heavily from Karl Marx and owes more to the German philosopher Martin Heidegger than to the Scottish philosopher and political economist Adam Smith. Loath to identify these sources—or perhaps unaware of them—neoconservatives do not acknowledge these intellectual underpinnings or their implications. Thus, in the final analysis, their critique is incoherent and even internally inconsistent. By not acknowledging and embracing their intellectual roots, neoconservatives are left with a deeply ambivalent and often confused view of biotechnology and the society that gives rise to it.
Antepartum Diagnosis and Management of in Utero Intestinal Volvulus with Perforation
Authors: Laxmi V. Baxi, Ming-Neng Yeh, William A. Blanc, John N. Schullinger
Journal: New England Journal of Medicine (1983)

IN recent years ultrasonography has contributed substantially to the prenatal diagnosis of various congenital malformations1 2 3 and thus revolutionized management in obstetric patients. The present case report describes the antepartum diagnosis of fetal ascites secondary to fetal small-bowel volvulus with perforation. Decompression of the distended fetal abdomen was carried out in utero by paracentesis under ultrasonographic guidance. This facilitated vaginal delivery and eliminated potential neonatal distress.Case ReportA 24-year-old black primigravida with an uncomplicated antepartum course and a normal ultrasonogram at 25 weeks of gestation subsequently had a minimal increase in amniotic-fluid volume at 34 weeks. Laboratory data including plasma . . .
A physiologic role for somatostatin 28 as a regulator of insulin secretion.
Authors: D A D'Alessio, C Sieber, C Beglinger, J W Ensinck
Journal: Journal of Clinical Investigation (1989)

Somatostatin 28 (S-28) is a peptide produced in the intestinal tract which rises in the circulation during nutrient absorption. We tested the hypothesis that S-28 regulates B-cell function by (a) studying the effects on insulin secretion of "physiologic" infusions of S-28 and (b) measuring insulin responses during elevated nutrient-stimulated endogenous S-28 levels. (a) Synthetic S-28 was infused on separate days into six healthy men at rates of 25 and 50 ng/kg per h which mimicked postprandial levels. Subjects were given a bolus of glucose (0.1 g/kg) after 120 min. Insulin responses during S-28 infusions were compared to a control study using a saline infusion in the same individuals. Glucose-stimulated insulin secretion was inhibited during the infusion of 50 ng/kg per h S-28 when compared to control (P less than 0.05). (b) Insulin secretion during elevations of endogenous S-28 was studied in healthy men who received a bolus of 2.5 g arginine (n = 14) or 25 U of secretin (n = 8) 120 min after swallowing 50 g fat, or, on a separate day, an equivalent volume of water. S-28 levels rose significantly after fat ingestion but did not change after water. Arginine and secretin-stimulated insulin secretion was inhibited following ingestion of fat compared with intake of water (P less than 0.05). Arginine-enhanced glucagon secretion was not changed by fat ingestion. We conclude that elevations in plasma S-28 levels, occurring during the postprandial state, attenuate B-cell secretion and this peptide may be a physiologic modulator of nutrient-stimulated insulin release.
Molecular evidence of an interaction between prenatal environmental exposures and birth outcomes in a multiethnic population.
Authors: Frederica P Perera, Virginia Rauh, Robin M Whyatt, Wei-Yann Tsai, John T Bernert, Yi-Hsuan Tu, Howard Andrews, Judyth Ramirez, Lirong Qu, Deliang Tang
Journal: Environmental Health Perspectives (2004)

Inner-city, minority populations are high-risk groups for adverse birth outcomes and also are more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene (BaP), and other polycyclic aromatic hydrocarbons (PAHs) found in urban air. In a sample of nonsmoking African-American and Dominican women, we evaluated the effects on birth outcomes of prenatal exposure to ETS, using questionnaire data and plasma cotinine as a biomarker of exposure, and environmental PAHs using BaP-DNA adducts as a molecular dosimeter. We previously reported that among African Americans, high prenatal exposure to PAHs estimated by prenatal personal air monitoring was associated with lower birth weight (p = 0.003) and smaller head circumference (p = 0.01) after adjusting for potential confounders. In the present analysis, self-reported ETS was associated with decreased head circumference (p = 0.04). BaP-DNA adducts were not correlated with ETS or dietary PAHs. There was no main effect of BaP-DNA adducts on birth outcomes. However, there was a significant interaction between the two pollutants such that the combined exposure to high ETS and high adducts had a significant multiplicative effect on birth weight (p = 0.04) and head circumference (p = 0.01) after adjusting for ethnicity, sex of newborns, maternal body mass index, dietary PAHs, and gestational age. This study provides evidence that combined exposure to environmental pollutants at levels currently encountered in New York City adversely affects fetal development.
Ankle joint synoviography in rheumatoid arthritis.
Authors: G Hug, A S Dixon
Journal: Annals of the Rheumatic Diseases (1977)

Twenty-six ankles of 23 patients with seropositive or negative arthritis and 24 ankles of 12 cadavers as a control group were studied by contrast synoviography. The main features in the patients were capsule enlargement, hypertrophic synovitis, and connections to tendon sheaths and to the posterior subtalar joint. None of the controls showed capsule distension or irregular outline of the joint cavity, but connections to tendon sheaths and/or to the posterior subtalar joint were present. Other features such as tibiofibular recess, early lymphatic filling, and joint destruction were seen.
NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS
Authors: John P. Fox
Journal: The Journal of Experimental Medicine (1943)

Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent. The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus. Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies. The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D(3)), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non-fatal infections, thus, may be important to the accuracy of quantitative determinations of infectivity. Limited observations with virus of the French neurotropic and the pantropic Asibi strains revealed that non-fatal infections do occur, but only rarely. Somewhat more extensive observations with unmodified virus of strains isolated from Brazilian cases of jungle yellow fever, in contrast, revealed an occurrence of non-fatal infections much greater than that observed with the most productive 17D substrains. With these jungle strains, the demonstration of non-fatal infections proved indispensable to any measure of the level of infectivity of virus preparations. The demonstration of the proportional occurrence in mice of non-fatal infections with yellow fever virus provides an additional means by which different virus strains and substrains may be characterized.
Changes in glucose tolerance after treatment for acromegaly.
Authors: V. Fonseca, P. Dandona, C. W. Havard
Journal: BMJ (1989)

show increased direct catabolism of VLDL apo- lipoprotein B without conversion to low density lipoprotein resulting in lower concentrations of total and low density lipoprotein cholesterol than in white people.Whether such compensatory mechanisms operate in other ethnic groups is not known, but the lipid/lipoprotein patterns found in Asians suggest that they do not.In Afro-Caribbean people (who currently have low rates of coronary disease) similar patterns to those in the Pima Indians are found, but in black Americans (in whom insulin resistance and high rates of coronary disease and diabetes now occur) the lipid profile is closer to that of white Americans.56Contrary to Professor Jarrett's negative view of current hypotheses, there is much in favour of the C peptide-insulin-atheroma link, particularly if data from in vitro experiments on insulin-like growth factors and homologous peptides are in- cluded.Refinements and novel approaches to these ethnic differences, rather than the guillotine, are required.Vive la difference!
Mental health legislation and decision making capacity: Capacity is of more than practical benefit
Authors: Brian J Murray
Journal: BMJ (2006)

Good quality monitoring is crucial for informed choiceEditor-In accordance with the patient choice scheme, all 303 primary care trusts in England were obliged from January 2005 to offer patients a choice of at least two providers for cataract surgery. 1 The scheme allows patients to be involved in how, where, and when they are treated.Providers can be NHS trusts, diagnostic and treatment centres, or independent sector providers from the UK or overseas.By February 2005 13 000 extra operations had already been performed under the independent sector treatment programme. 2However, concern was raised about variations in clinical safety between different providers. 3 We sent a postal questionnaire to the leaders of patient choice for each of the primary care trusts in England asking how they monitor the quality of care from their providers.The table shows the replies from 125 trusts.The quality monitoring of providers by primary care trusts is poorly structured and variable.Who then should monitor standards and what variables should they use?Traditionally, NHS providers have used audit and clinical governance to measure their performance.Should it now be the role of the Strategic Health Authority, the provider, or the purchaser in the form of primary care trusts to monitor the product offered to the patient?Information technology exists to collect accurate data about adverse events in addition to visual acuity and refractive outcomes.The public expect that safe cataract care should be commissioned for them, 4 and robust methods of monitoring need to be agreed and implemented so that patients can make a truly informed choice.These decisions need to be made not only for cataract surgery but also for other elective procedures that will increasingly be made available to patients through the patient choice scheme.