tbuckley/cabot-search huggingface dataset:
Weighing the Alternatives
Authors: Kenneth D. Gardner
Journal: Annals of Internal Medicine (1999)

Letters15 June 1999Weighing the AlternativesKenneth D. Gardner Jr., MDKenneth D. Gardner Jr., MDUniversity of New Mexico School of Medicine; Albuquerque, NM 87131 (Gardner)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-12-199906150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. Davidoff's provocative editorial on the paradoxes of alternative care (1) poses the question, “What can be learned … ?” An answer relevant to this query emerged from a 1980 point-counterpoint debate on the merits of holistic medicine.The event was sponsored by the American Association for the Advancement of Science as part of its Congressional Science Fellowship program. It featured the contrasting views of a practitioner of orthodox medicine, recruited from the upper echelons of the American Medical Association, and those of a former homemaker who had opened a clinic for holistic medicine after receiving a ...Reference1. Davidoff F. Weighing the alternatives: lessons from the paradoxes of alternative medicine [Editorial]. Ann Intern Med. 1998;129:1068-70. LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of New Mexico School of Medicine; Albuquerque, NM 87131 (Gardner) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 June 1999Volume 130, Issue 12Page: 1030KeywordsFellowshipsTraditional medicineVision Issue Published: 15 June 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Biliary bile acids in cholelithiasis and colon cancer.
Authors: W M Castleden, P Detchon, N L Misso
Journal: Gut (1989)

The role of biliary deoxycholate as an endogenous colon carcinogen and the possible association between cholelithiasis and/or cholecystectomy and the subsequent development of large bowel cancer is unclear. This paper describes biliary bile acids analysis performed on 13 patients undergoing cholecystectomy for gall stones, 10 patients undergoing colonic resection for colon cancer, and eight control patients. For all 31 patients the total bile acids concentration was highly variable (8.3 mg/ml-106.5 mg/ml). The median ratio of primary to secondary bile acids was 2.7:1. The biliary bile acid ratios were similar in both control patients (3.7:1) and those with colon cancer (3.1:1), whereas patients with gall stones had significantly higher secondary bile acid levels in their biliary bile (ratio 1.9:1, p = less than 0.05). This result indicates that raised biliary deoxycholate concentrations are not present in patients with colon cancer and are therefore unlikely to be a major predisposing factor in the aetiology of this disease. It is unlikely that cholelithiasis and/or cholecystectomy predispose to the subsequent development of colon tumours.
Glutathione reductase deficiency in a kindred with hereditary spherocytosis
Authors: Koji Nakashima, Katsuyo Yamauchi, Shiro Miwa, Kingo Fujimura, Akiko Mizutani, Atsushi Kuramoto
Journal: American Journal of Hematology (1978)

Abstract A kindred with hereditary spherocytosis was found to have erythrocyte glutathione reductase deficiency. The glutathione reductase was evaluated enzymatically and immunologically. The enzyme activity could not be restored either by flavin adenine dinucleotide (FAD) in vitro, or by oral administration of FAD. Kinetic and electrophoretic studies, heat stability tests, and pH curves revealed no evidence of a variant enzyme. The results of electroimmunodiffusion and neutralization tests using an antiserum indicated that the deficiency is caused by a diminished production of enzyme protein. Hereditary spherocytosis and glutathione reductase deficiency traits segregated independently. The amount of reduced glutathione in the erythrocyte was normal, and the deficiency state without hereditary spherocytosis was asymptomatic. All deficient members in this kindred were heterozygous and the residual enzyme activity in the heterozygote might be sufficient to maintain the reduced glutathione level to prevent oxidative stress.
Secretin and Calcium Provocative Tests in the Zollinger-Ellison Syndrome
Authors: Harold Frucht
Journal: Annals of Internal Medicine (1989)

Study Objective: To evaluate criteria of positivity for and usefulness of both the secretin and calcium gastrin-provocative tests in patients with the Zollinger-Ellison syndrome. Design: Prospective trial in consecutive patients. Setting: Referrals to a clinical research center. Patients: Consecutive sample of 80 patients with the Zollinger-Ellison syndrome. Intervention: Kabi-secretin (2 U/kg body weight) given by intravenous bolus and calcium gluconate (10%) (54 mg/kg · h [5 mg/kg · h of calcium]) given by continuous intravenous infusion for 3 hours. Serum gastrin measured at -15, and -1 minutes before, and 2, 5, 10, 15, 20, and 30 minutes after secretin, or every 30 minutes for 3 hours during the calcium infusion. Serum calcium and serum gastrin were measured simultaneously during the calcium infusion. Measurements and Main Results: There was no significant difference in the responses of patients with different extents or locations of the tumor, presence or absence of multiple endocrine neoplasia, type-I, or with fasting gastrin less than or greater than 1000 pg/mL. In patients with fasting gastrin of less than 1000 pg/mL, the sensitivity of the secretin test using the criterion of an increase in gastrin of at least 110 pg/mL was 93% (CI, 76% to 99%) and for an increase of 200 pg/mL it was 85% (CI, 66% to 96%), (P > 0.05). With the calcium infusion test, the sensitivity using the criterion of an increase of 395 pg/mL was 43% (CI, 23% to 66%) and for an increase of 50% was 74% (CI, 52% to 90%), (P < 0.01). The calcium infusion test was positive in 33% of patients with a negative secretin test. With the secretin test, 75% of patients had a positive response by 5 minutes, 95% by 10 minutes, 100% by 15 minutes, and 6% only at 2 minutes. With calcium infusion, patients had positive responses at 120 to 180 minutes. Conclusions: The secretin test is preferred over the calcium test because of its greater sensitivity and simplicity. The recommended criteria are a 200 pg/mL increase for the secretin test and a 395 pg/mL increase for the calcium test. The calcium test should be reserved for patients having a negative secretin test, gastric acid hypersecretion, and a strong clinical suspicion of the Zollinger-Ellison syndrome.
Tooke report proposes a new body to get postgraduate medical training back on track
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

England needs a new body to oversee and champion postgraduate medical education to overcome the “many deficiencies” of the Modernising Medical Careers (MMC) programme, recommends the inquiry into the failed attempt to reform junior doctors’ training.

A new body would be key to ensuring that specialist training in England gets back on track, says the report. It should be “rapidly formed to redefine the guiding principles that should govern the nature and conduct of postgraduate medical education and training in the future”—something that MMC lacked, it says.

The final report of John Tooke’s inquiry says that the new body, which would be called NHS Medical Education England, should have ringfenced funding and be outside the control of the Department of Health.

The inquiry was ordered in April 2007 by the then health secretary, Patricia Hewitt, after one of the …
γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas
Authors: M. E. Martinez-Escala, M. Sidiropoulos, J. Deonizio, P. Gerami, M.E. Kadin, J. Guitart
Journal: British Journal of Dermatology (2014)

T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate.To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL).A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed.Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16 months (range 3-64), showing an indolent clinical course in all cases.The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample.
Impact of Toxicity Assumptions on Socioeconomic Analysis of Breast Cancer Chemotherapy
Authors: Ira E. Felman
Journal: Journal of Clinical Oncology (2007)

The authors failed to list Doxil (generically known as doxorubicin; Ortho Biotech Products, Bridgewater, NJ) in Table 1, which presented the new oncology drugs approved in the United States from 1990 to 2005.While this omission may seem trivial, it is not if one considers that Doxil was the first accelerated oncology drug approval and helped usher in an era of rapid drug approvals based on the surrogate marker, tumor response.Having defended Doxil before the Oncology Drug Advisory Committee leading to its approval, I have become keenly aware of the advantages and disadvantages of the accelerated approval process.As we now know, tumor shrinkage is not always a surrogate for improved survival or quality of life.Another major point overlooked in this review was that many industry sponsors of oncology drugs approved by this process have failed to submit confirmatory, postapproval trials as required under the accelerated approval process.Coupled with the high cost these drugs put on the health care system, many are left to think that commercial companies have abused the opportunity provided by the accelerated approval process.However, as oncologists, we all want promising therapies available for our patients as early as possible.Perhaps we should consider keeping the accelerated approval process available while restricting the reimbursement to the company until randomized, controlled trials showing an effect of survival or quality of life have been conducted.Alternatively, US oncologists must fully support phase III, randomized clinical trials comparing experimental therapies to best supportive care when there are no approved therapies for the indicated patient population.
Can Human Hematopoietic Stem Cells Become Skin, Gut, or Liver Cells?
Authors: Janis L. Abkowitz
Journal: New England Journal of Medicine (2002)

Hematopoietic stem cells maintain hematopoiesis and reestablish blood-cell production after bone marrow transplantation. Abnormal clonal expansion of these stem cells may result in chronic myelogenous leukemia, polycythemia vera, and the myelodysplastic syndromes. Stem cells also exist in other regenerating tissues and are considered tissue-specific: neural stem cells give rise to neurons, astrocytes, and oligodendrocytes; gastrointestinal stem cells give rise to absorptive, secretory, and endocrine cells within the gut.In contrast, embryonic stem cells, derived from the inner layer of the blastocyst (the stage of development that occurs seven to eight cell divisions after the egg is fertilized), are totipotent and . . .
Endogenous Creatinine Clearance as a Clinical Measure of Glomerular Filtration Rate
Authors: W. M. Bennett, G. A. Porter
Journal: BMJ (1971)

Endogenous creatinine clearance was assessed by inulin in 91 simultaneous studies in 41 patients and proved an accurate measurement of glomerular filtration rate. For filtration rates <20 ml/min the creatinine clearance may slightly overestimate the glomerular filtration rate. Successive determinations of filtration rate by either method may vary by 20% even though the methods agree with each other. Glomerular filtration rate itself is variable, and in its clinical usage this should be recognized.
Relapsing Polychondritis, a "Floppy" Mitral Valve, and Migratory Polytendonitis
Authors: DAVID A. HEMRY
Journal: Annals of Internal Medicine (1972)

A patient with relapsing polychondritis, the "floppy" mitral valve syndrome, retinal artery thrombosis, and a migratory polytendonitis is described, and an histological similarity of the aortic lesions of polychondritis to the mitral valve lesions of the "floppy" mitral valve syndrome is discussed. We suggest that the pathologic process of polychondritis, which was seen in the ear biopsy, may also occur in the mitral valve or its support apparatus and explain the cardiac findings.
Therapeutic Agents for Human Skin Infestations
Authors: Donald G. W. Brooking
Journal: JAMA (1975)

To the Editor.—  Apropos of Dr. Howard I. Maibach's answer to Dr. Robert L. Devine's query regarding therapeutic agents for human skin infestations (230:759, 1974), I would like to modify parts four and five of his answer as follows.  I don't believe that as dermatologists we ought to be recommending preparations for what is essentially pest control. Also, I doubt that any people other than professional pest control people should be using these products unsupervised. When fleas or bedbugs are suspect, my advice to patients is always to call their friendly exterminator.
Loss of CTL Function among High-Avidity Tumor-Specific CD8+ T Cells following Tumor Infiltration
Authors: Claire N. Janicki, S. Rhiannon Jenkinson, Neil A. Williams, David J. Morgan
Journal: Cancer Research (2008)

Abstract A major problem in generating effective antitumor CTL responses is that most tumors express self-antigens to which the immune system is rendered unresponsive due to mechanisms of self-tolerance induction. CTL precursors (CTLp) expressing high-affinity T-cell receptors (TCR) are often functionally deleted from the repertoire, leaving a residual repertoire of CTLp having only low-affinity TCR. Furthermore, even when unique antigens are expressed, their presentation by dendritic cells (DC) may predispose to peripheral tolerance induction rather than the establishment of CTL responses that kill tumor cells. In this study, we examined both high-avidity (CL4) and low-avidity (CL1) CD8+ T-cell responses to a murine renal carcinoma expressing, as a neoantigen, high and low levels of the hemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8; RencaHAhigh and RencaHAlow). Our data show that, following encounter with KdHA epitopes cross-presented by bone marrow–derived DC, low-avidity CL1 cells become tolerized within tumor-draining lymph nodes (TDLN), and in mice bearing either RencaHAhigh or RencaHAlow tumors, very few form tumor-infiltrating lymphocytes (TIL). In marked contrast, high-avidity CL4 cells differentiate into effector CTL within the TDLN of mice bearing either RencaHAhigh or RencaHAlow tumors, and although they form TIL in both tumors, they lose CTL effector function. Critically, these results show that anticancer therapies involving either adoptive transfer of high-avidity tumor-specific CTL populations or targeting of preexisting tumor antigen–specific memory CD8+ T cells could fail due to the fact that CTL effector function is lost following tumor infiltration. [Cancer Res 2008;68(8):2993–3000]
Models of amino acid substitution and applications to mitochondrial protein evolution
Authors: Z. Yang, R. Nielsen, M. Hasegawa
Journal: Molecular Biology and Evolution (1998)

Models of amino acid substitution were developed and compared using maximum likelihood. Two kinds of models are considered. "Empirical" models do not explicitly consider factors that shape protein evolution, but attempt to summarize the substitution pattern from large quantities of real data. "Mechanistic" models are formulated at the codon level and separate mutational biases at the nucleotide level from selective constraints at the amino acid level. They account for features of sequence evolution, such as transition-transversion bias and base or codon frequency biases, and make use of physicochemical distances between amino acids to specify nonsynonymous substitution rates. A general approach is presented that transforms a Markov model of codon substitution into a model of amino acid replacement. Protein sequences from the entire mitochondrial genomes of 20 mammalian species were analyzed using different models. The mechanistic models were found to fit the data better than empirical models derived from large databases. Both the mutational distance between amino acids (determined by the genetic code and mutational biases such as the transition-transversion bias) and the physicochemical distance are found to have strong effects on amino acid substitution rates. A significant proportion of amino acid substitutions appeared to have involved more than one codon position, indicating that nucleotide substitutions at neighboring sites may be correlated. Rates of amino acid substitution were found to be highly variable among sites.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: John E. Coe, S. B. Salvin
Journal: The Journal of Experimental Medicine (1963)

"Gastric feeding" of adult guinea pigs with dinitrochlorobenzene (DCB) resulted in a specific unresponsiveness to sensitization with the specific contact hapten. The more DCB gastric-fed to a guinea pig, the more complete the unresponsiveness to the hapten. When mycobacteria were incorporated into the sensitizing emulsion, the state of unresponsiveness to the dinitrophenyl (DNP) group was less apparent. When animals gastric-fed with DCB were later sensitized with an in vitro conjugate of the hapten combined with a heterologous protein such as dinitrophenyl-hen egg albumin (DNP.HEA), an immune response similar to that in the controls occurred both to the hapten and to the protein carrier. However, when the tolerant animals were sensitized with a conjugate containing a homologous protein carrier such as dinitrophenyl guinea pig serum (DNP.GPS), they showed diminished immune responses in comparison with those in the non-tolerant controls. The presence of circulating anti-DNP antibodies from sensitization with DNP-HEA did not affect the unresponsiveness to the specific contact hapten, regardless of whether these antibodies are present before or after induction of tolerance. Sensitization with picryl chloride (PiCl) (a cross-reacting hapten), either before or after gastric feeding of DCB, did not affect the state of unresponsiveness to DNP. Similarly when the DNP-tolerant animal was sensitized with PiCl, the subsequent immune response was similar to that in the controls; cross-reactions with the DNP group both in the contact and circulating antibody phase occurred at a rate similar to that in the controls. The foregoing relationships can be explained by presuming that, upon the gastric feeding of DCB, an in vivo conjugate is formed with a somatic protein, which determines the basic specificity of the tolerance. Acquired tolerance seems to manifest an immunologic specificity similar to that of delayed hypersensitivity, a relationship not unexpected if delayed hypersensitivity is an early phase of the immune response.
EUS for portal hypertension: a comprehensive and critical appraisal of clinical and experimental indications
Authors: M. El-Saadany, S. Jalil, A. Irisawa, G. Shibukawa, H. Ohira, M. Bhutani
Journal: Endoscopy (2008)

Endoscopic ultrasonography (EUS) has significantly improved our understanding of the complex vascular structural changes that occur in portal hypertension and their clinical and prognostic significance. EUS in combination with color Doppler technique enables us to study the hemodynamic changes in the portal venous system noninvasively, and to determine objectively the effect of different pharmacological agents on portal hypertension. EUS has also found some role in the treatment and follow up of esophageal and gastric varices. It may play a clinical role in the diagnosis of gastric, duodenal, and rectal varices. Recently reported EUS-based devices that measure variceal wall tension and intravariceal pressure noninvasively could have an impact on the identification of patients at high risk of variceal bleeding with the aim of initiating prophylactic treatment, and in the assessment of patients' responses to drug therapy of portal hypertension. EUS is occasionally very helpful in the clinical management of portal hypertension. It is an interesting and important research tool for many experimental indications that are not routinely applied in clinical practice at this time.
Abstract P5-17-07: Influence of bevacizumab on local-regional recurrence in triple negative breast cancer
Authors: BM Prendergast, JF De Los Santos, OC Barrett, A Forero, CI Falkson, MM Urist, H Krontiras, KI Bland, RF Meredith, KS Keene, Z You, JT Carpenter
Journal: Cancer Research (2012)

Abstract Background: Triple negative breast cancer (TNBC) comprises 15–20% of newly diagnosed invasive breast cancers and has been associated with an elevated risk of both local-regional recurrence (LRR) as well as distant failure. Bevacizumab (BEV) has been shown to improve pathologic complete response rates in the setting of neoadjuvant chemotherapy (NCT), but its effect on LRR remains undefined. This study reports the impact of adding BEV to standard breast cancer therapy in TNBC patients treated at a single institution. Methods: One hundred and eighty-five consecutive TNBC patients treated at the University of Alabama Birmingham from May 2005 to August 2010 were reviewed. Thirty-one TNBC patients treated with chemotherapy (CT) and BEV on prospective studies were matched (1:2) with 62 TNBC patients treated with CT alone, controlling for age, stage, and use of radiation (RT). The Kaplan-Meier method was used to estimate LRR, distant metastasis-free survival (DMFS), and overall survival (OS), and cohorts were compared using Cox proportional hazards models and the 2-sided log-rank test. Results: Mean age was 47 and 46 years in the cohorts with and without BEV, respectively. Stage in each cohort was as follows: 32% stage I, 61% stage II, and 7% stage III. Use of adjuvant RT was 81% in each cohort (25/31 BEV, 50/62 no BEV). BEV was delivered with NCT in 17 patients (55%) and with adjuvant CT in the remaining 14 patients (45%). Eleven patients (35%) completed an additional 1 year of maintenance therapy with BEV. LRR occurred in 2 (6%) patients treated with BEV vs. 16 (26%) treated with CT alone (HR = 0.25, 95% CI 0.06–1.07, p = 0.04). Distant recurrence occurred in 3 (10%) patients treated with BEV vs. 11 (18%) patients in the CT group HR=0.6, 95% CI 0.2–1.8, p = 0.48). There were 2 (6%) deaths in the BEV group vs. 12 (19%) in the CT alone group (HR = 0.55, 95% CI 0.13–2.3, p = 0.19). Conclusions: In a matched-pair analysis of TNBC patients, the addition of BEV to conventional breast cancer management was associated with a reduction in LRR. Further prospective study is necessary to examine the impact of BEV on local-regional control in TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-07.