tbuckley/cabot-search huggingface dataset:
Melanoma--Part 2: management
Authors: C. Thirlwell, P. Nathan
Journal: BMJ (2008)

#### Summary points

Most melanomas that are detected and treated early are cured. However, advanced disease carries a dismal diagnosis, and timely intervention from members of the multidisciplinary skin cancer team at all stages of the disease is essential to maximise cure rates. The management of patients with incurable disease is highly specialised and requires the input of surgeons, medical and clinical oncologists, palliative care teams, and clinical nurse specialists. In the second of this two part series on melanoma we review its management from primary lesion through to metastatic disease.

#### Sources and selection criteria

We used Medline (1966-2008), Cochrane Library, and Embase (1980-2008) to identify studies and meta-analyses for this review. The search string included the terms melanoma, adjuvant and metastatic therapy, wide local excision, and sentinel lymph node biopsy. We accessed the websites of the National Institute for Health and Clinical Excellence, National Cancer Research Network, and National Cancer Research Institute for guidelines and current trials in the United Kingdom. 

In the past, suspicious lesions were often removed in primary care. However, recent national guidance recommends that patients with suspicious pigmented lesions are referred to a specialist member of the hospital based skin cancer team using the two week cancer wait procedure.1 2 This has been the subject of much debate and if fully implemented will result in a change in practice for many general practitioners.

Primary melanoma is often difficult to diagnose, even for those with a specialist training. A prospective study showed …
Extended Preservation of Human Liver Grafts With UW Solution
Authors: Satoru Todo
Journal: JAMA (1989)

The fate of 185 cadaveric liver homografts preserved for four to 24 hours with University of Wisconsin (UW) solution was compared with that of 180 grafts preserved for three to 9 1/2 hours with conventional Euro-Collins solution. Although the average preservation time of the UW-preserved livers was almost twice as long as that of the Euro-Collins-preserved livers, the UW-preserved grafts survived at a higher rate; permitted equal patient survival; and had a lower rate of primary nonfunction, a reduced need for retransplantation, and a lower rate of hepatic artery thrombosis. There was no correlation between the time of preservation of UW-preserved grafts up to 24 hours and liver function abnormalities in the first postoperative week. In contrast, livers preserved with Euro-Collins solution for more than five hours had significantly increased perturbations of hepatic function tests. The potential revolutionary effect of the UW solution on liver transplantation is described herein. (<i>JAMA</i>1989;261:711-714)
All About Gray Cats
Authors: Theodore Kamholtz
Journal: JAMA (1974)

To the Editor.—  I would like to report the findings of an interesting study performed at the Newton Irwin General Hospital at Tattleboro (NIGHT). Our town is very proud of Newton Irwin, whom history records as the originator of baked beans, making Tattleboro the borborygmus capital of the world.  Whether as cause or effect, the most common admission diagnosis at our hospital is abdominal tympany (AT), divided (of course) into acute abdominal tympany (AAT) and chronic abdominal tympany (CAT).  During the first six months of 1973, it was decided to test the saliva of all patients admitted for AT with Gombarts reducing agent (GRA). As medical students will remember, a drop of GRA added to saliva will remain clear if the test is negative (GRAN), but will turn yellow (GRAY) if the test is positive.  It is found generally, that AATs were GRAN, but at NIGHT all CATS were GRAY.
AN EXPERIMENT TO ILLUSTRATE THE EFFECT OF SIZE OF POPULATION ON THE RATE OF SELECTION OF NEW BACTERIAL RACES
Authors: W. J. Penfold
Journal: BMJ (1913)

ICheemical Analysis.The viscera of the deceased, and a small quantity of urine found in his bladder were forwarded to me for chemical analysis, and I detected cocaine in both.I could detect no other poison in the viscera.The dose taken by the deceased could not be ascertained.CASE II.K., a Hindu female, aged abotut 28 years, a woman of the town, wvas in the habit of taking cocaine.She left home at about 1.30 am-n.oni August 29th, 1912, and returned at 6.30 a-m. a few hours later.She was seen to be staggering while washing her mouth at a hydrant hard bv.Very soon afterwards she lay dowvn, became unconscious, and in a few minutes she died.Post-mortem Appearances.Body fairly nourished; rigor mortis present; pupils sliglhtly cointracted; there were no marks of violence on the body.The brain and its membranes, the liver, the spleen, the kidneys, the ovaries, the bladder, and the mucous membrane of the stomach were found congested.The right heart was dilated, and contained dark fluid blood.The stomach contained about 3 oz. of recently taken vegetable food without special odour.Cheemical Anialysis.Tlle viscera in the case were sent to me for chemical analysis, and I detected a marked quantity of cocaine in them.I detected no other poison in the viscera.Neither the dose taken nor the fatal period could be ascertained in this case.CASE III.M. K., a Hindu female, aged about 20 years, lived with her husband in Calcuttta.On October 17th, 1912, she visited her
Bone Imaging in Patients with Unexpected Elevation of Serum Alkaline Phosphatase
Authors: CARYL G. SALOMON, AMJAD ALI, ERNEST W. FORDHAM
Journal: Clinical Nuclear Medicine (1989)

Radionuclide bone imaging frequently is requested to evaluate clinically unexpected persistent elevations in serum alkaline phosphatase. To assess the efficacy of this practice, the authors reviewed bone images obtained for this purpose during a 12-month period and correlated the results with clinical data. One hundred nineteen patients were included in the study. Arthritic changes were the abnormalities most frequently present on the bone images. Several cases of occult bone metastasis, Paget's disease, and trauma were also detected in this group of patients. The authors continue to recommend bone imaging in patients with unexpected elevation of serum alkaline phosphatase; however, further prospective studies with larger and different patient populations are needed to justify this practice in the present era of cost-effectiveness.
Severe haemolytic anaemia in pregnancy in nigerians treated with prednisolone
Authors: A. F. Fleming, N. C. Allan
Journal: BMJ (1969)

Haemolytic anaemia of obscure aetiology is a common complication of pregnancy in Nigeria. Treatment with antimalarials and folic acid is usually followed by a rapid remission, but response is slow in about 25% of patients and haemolysis continues uncontrolled in about 5%. The administration of prednisolone to six patients with uncontrolled haemolysis was followed by rapid recovery in five and possible benefit in one. Risks of prednisolone therapy to the mother appear to be slight and outweighed by the risks of continued severe anaemia and frequent blood transfusions. There seemed to be no appreciable increase of fetal loss compared with that in anaemic pregnancies not treated with prednisolone.
Weight and Diabetes
Authors: Sharon Parmet, Cassio Lynm, Richard M. Glass
Journal: JAMA (2006)

Weight and Diabetes Diabetes is a common disorder in which the body has difficulty controlling levels of sugar in the bloodstream.Normally, the hormone insulin made by the pancreas (an organ in the abdomen) regulates blood sugar levels.The bodies of individuals with type 1 diabetes, which usually starts by the early teen years, do not make enough insulin to control blood sugar, so they must receive insulin injections.The bodies of persons with type 2 diabetes are resistant to the effects of insulin.Type 2 diabetes, also known as "adult-onset" diabetes, usually develops in adulthood but can also occur in overweight children.Family history of diabetes and excess weight, especially weight carried around the middle, are strong risk factors for developing type 2 diabetes.Losing weight greatly reduces your chances for type 2 diabetes and can help bring your blood sugar under control if you already have type 2 diabetes.Type 2 diabetes can be treated with diet, exercise, and oral prescription medications but may require insulin shots.The March 15, 2006, issue of JAMA includes an article about type 2 diabetes.This Patient Page is based on one previously published in the August 25, 2004, issue of JAMA.
EARLY RESULTS AFTER ENDOVASCULAR MITRACLIPTM REPAIR OF SEVERE MITRAL VALVE REGURGITATION IN PATIENTS WITH END-STAGE HEART FAILURE
Authors: Sven T. Pleger, Ulrike Krumsdorf, Marius Schulz-Schoenhagen, Emanuel Chorianopoulos, Christian Zugck, Wolfgang Rottbauer, Hugo A. Katus, Raffi Bekeredjian
Journal: Journal of the American College of Cardiology (2011)
Medical students. Great Britain.
Authors: R Frackowiak
Journal: BMJ (1973)

XpertMTB/RIF is a rapid molecular diagnostic tool detecting MTB and RIF-susceptibility within two hours. However, indeterminate RIF-susceptibility results occur and cause uncertainty about clinical judgment. <b>Objective:</b> To evaluate the level of indeterminate RIF-susceptibility results by XpertMTB/RIF, to assess the RIF-susceptibility of such strains and to determine the method that should be used for reference. <b>Methods:</b> Sputum from patients with TB diagnosed in Azerbaijan prisons during 2013-2015 were directly examined by XpertMTB/RIF. Strains with indeterminate RIF-susceptibility results were examined with MGIT-based DST and <i>rpoB</i> sequencing. For comparison, frozen MGIT cultures collected from other TB patients at diagnosis during 2010-2012 were revived and examined with XpertMTB/RIF retrospectively. <b>Results:</b> Of 275 samples examined with XpertMTB/RIF directly and of 232 revived cultures examined retrospectively, 8(2.9%) and 0 had indeterminate RIF-susceptibility results, respectively (p=0.009). MGIT results indicated full concordance with sequencing among the samples showing indeterminate RIF-susceptibility results by XpertMTB/RIF. <b>Conclusion:</b> The indeterminate RIF-susceptibility detected on sputum samples directly by XpertMTB/RIF is significant. However, this drawback may be resolved with the use of Xpert MTB/RIF on cultures. MGIT may be referred to in cases of indeterminate RIF-susceptibility by XpertMTB/RIF.
Immunochemotherapy of Cancer with Chlorambucil-carrying Antibody
Authors: T. Ghose, S. T. Norvell, A. Guclu, D. Cameron, A. Bodurtha, A. S. MacDonald
Journal: BMJ (1972)

Cell-surface localizing heterologous antibodies against the mouse EL4 lymphoma and a human malignant melanoma could be bound to chlorambucil without causing the loss of the alkylating activity of chlorambucil or interfering with the reactivity of the antibodies with their respective tumour cells. When given to mice preinoculated with tumour cells 2, 24, 72, and 120 hours before the beginning of treatment the chlorambucil-bound antibody was a much more effective tumour inhibitor than chlorambucil or the antibody alone. In a patient with disseminated malignant melanoma injection of the chlorambucil-bound anti-melanoma antibody first locally into a few metastatic nodules and then by the intravenous route was followed by the regression of all the metastatic nodules.
TECHNETIUM-99m SESTAMIBI SPECT IN DIAGNOSING CORONARY ARTERY DISEASE IN A COMMUNITY HOSPITAL
Authors: D. Fink-Bennett, H. R. Balon, B. Berman, R. Igram, M. Barsamian, J. E. Juni
Journal: Clinical Nuclear Medicine (1992)

Fink-Bennett, D.; Balon, H. R.; Berman, B.; Igram, R.; Barsamian, M.; Juni, J. E. Author Information
Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses
Authors: Qiang Zhang, Sudin Bhattacharya, Rory B. Conolly, Harvey J. Clewell, Norbert E. Kaminski, Melvin E. Andersen
Journal: Environmental Health Perspectives (2014)

Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations.Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data.Here we have examined dose-response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures.Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays.
Methotrexate for Psoriasis
Authors: Gerald D. Weinstein
Journal: JAMA (1973)

The therapy of severe refractory psoriasis with the folic acid antagonist, methotrexate, recently received Food and Drug Administration approval. The folic acid antagonists were first used for psoriasis in 1951, and since then an extensive literature has attested the efficacy of methotrexate for treating various forms of psoriasis and psoriatic arthritis. Most studies indicate that about three fourths of patients treated for psoriasis enjoy good to excellent results. Methotrexate, it should be emphasized, is useful only for the control of psoriasis and is not curative.  Psoriasis is a cutaneous disease characterized by a markedly increased rate of epidermal cell proliferation. Methotrexate, acting as an inhibitor of DNA synthesis by blocking dihydrofolic reductase, prevents cell reproduction in the psoriatic lesion, allowing the skin to return to normal function. Since methotrexate is administered systemically, other proliferating cell compartments, ie, bone marrow, gastrointestinal tract, and hair, are subject to possible drug effects. It
Tuberculin Skin Testing
Authors: John T. Flynn
Journal: Annals of Internal Medicine (1997)

Letters15 August 1997Tuberculin Skin TestingJohn T. Flynn, MDJohn T. Flynn, MDNew York Downtown Hospital; New York, NY 10038Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-4-199708150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The reliability of the tuberculin skin test depends not only on accurate measurement [1] but also on proper administration. The Mantoux technique [2] requires an intradermal injection, not a subcutaneous one. In addition to measurement of the resulting reaction, the patient should be asked whether the initial injection raised a sharply demarcated, painful blister at the needle site. Too often, inexperienced or inadequately instructed administrators inject the test material subcutaneously; the reaction is therefore mild and local, subsiding and even disappearing within the requisite 72 hours. This leads to an inappropriate reading and an inadequate evaluation of ...References1. Pouchot J, Grasland A, Collet C, Coste J, Esdaile JM, Vincenaux P. Reliability of tuberculin skin test measurement. Ann Intern Med. 1997; 126:210-4. Google Scholar2. Mantoux C. Lintradermo-reaction a la tuberculine et son interpretation clinique. La Presse Med. 1910; 18:10-3. Google Scholar Author, Article, and Disclosure InformationAffiliations: New York Downtown Hospital; New York, NY 10038 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1997Volume 127, Issue 4Page: 334KeywordsBlistersIntradermal injectionsProphylaxisSkin testsTuberculin Issue Published: 15 August 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
SURGICAL TREATMENT OF BULLOUS EMPHYSEMA
Authors: John L. Kee
Journal: JAMA (1960)

The results of treatment for bullous emphysema were studied in 37 patients. One group consisted of patients having large air cysts with poor or intermittent bronchial communication and apparently normal remaining lungs. Resection of the bulla was strikingly beneficial in some patients of this group, and eight patients were changed from severe respiratory cripples to essentially normal persons by operation. The other group consisted of patients with air cysts with poor or intermittent bronchial communication but varying degrees of emphysema in the remaining lungs. All patients with poor results were in this group. Good results depend on the selection of patients with definite symptoms, localized disease, and an emphysematous bulla or bullae occupying at least the area of one lobe of one lung. Case histories and spirometric data from four patients illustrate these points.
Analysis at the sequence level of mutations induced by the ultimate carcinogen N-acetoxy-N-2-acetylaminofluorene
Authors: Robert P. P. Fuchs, Nicole Schwartz, Michel P. Daune
Journal: Environmental Health Perspectives (1983)

The covalent binding of an ultimate carcinogen to the DNA bases or phosphate groups creates a premutational lesion that in vivo is processed by the repair, replication and recombination enzymes, and eventually may be converted into a mutation. Being interested in the way that an initial premutational event is converted into a stable heritable mutation, we have sequenced stable mutations in a gene that has formed covalent adducts in vitro with N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF, a model for the ultimate metabolite of the rat liver carcinogen 2-acetylaminofluorene, AAF). In vivo studies have shown the mutagenicity of AAF and its derivatives in both bacterial and eukaryotic systems. N-AcO-AAF reacts in vitro with DNA leading mainly to the formation of a guanine adduct, N-2-(deoxyguanosin-8-yl)-acetylaminofluorene (80%) and to at least three minor adducts. Studies by our group showed that binding of N-AcO-AAF to DNA resulted in a local distortion of the DNA helix around the C-8 adduct (the insertion-denaturation model). We describe here the analysis of forward mutations induced in the tetracycline-resistance gene of pBR322 by directing the chemical reaction of the carcinogen to a small restriction fragment (BamHI-SalI) inside the antibiotic-resistance gene. Mutants are selected for ampicillin (Ap) resistance and tetracycline (Tc) sensitivity. The plasmid DNA of such mutants was analyzed for sequence changes in the fragment where the AAF binding had been directed. We show here that the mutations are mainly frameshifts involving GC base pairs and that certain base pairs (hotspots) are affected at high frequencies.
Where's the Bias?
Authors: Leo E. Hollister
Journal: Annals of Internal Medicine (1998)

Letters1 January 1998Where's the Bias?Leo E. Hollister, MDLeo E. Hollister, MDUniversity of Texas Medical School; Houston, TX 77225Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-1-199801010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. Davidoff's editorial, “Where's the Bias?” [1], describes a reasonable approach to increasing problems of bias and conflict of interest in medical publications. It is essentially a plea for common sense.I recently submitted a review paper to a highly respected journal. As was the requirement for submission, I indicated in the cover letter that I was unaware of any possible conflicts or bias. The journal seemed to be impressed enough with the paper to make inquiries about the completeness of a couple of references, as well as a suggestion to reduce the length. After the revision ...References1. Davidoff F. Where's the bias? [Editorial] Ann Intern Med. 1997; 126:986-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Medical School; Houston, TX 77225 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByVerkoudheid 1 January 1998Volume 128, Issue 1Page: 75KeywordsConflicts of interestDrugs Issue Published: 1 January 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Patient and Physician
Authors: Robert A. Gatter
Journal: JAMA (1971)

<h3>To the Editor.—</h3> What has happened to the patient and the physician? As I look over the articles in this journal and others, including nonmedical publications, regarding health programs, I can only find health-care provider and health-care consumer. I remember the days when I was considered a customer in the local stores. Suddenly, I became an impersonal consumer, something to be dealt with by number. I rationalized this by saying that, at least in my own area, my patients will always be patients, and now I find that this sanctity is being threatened also. I cannot see that any good has come from my being a consumer, and I am quite sure that no good will come from patients being considered consumers. At a time when the youth of our country is protesting dehumanization, it seems that this same process is seeking one of the last strongholds of a humanistic
Peritoneal Carcinomatosis of Unknown Primary Site in Women
Authors: Charles M. Strnad
Journal: Annals of Internal Medicine (1989)

To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces.Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984.All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease.In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients).The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months).Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.