tbuckley/cabot-search huggingface dataset:
Opportunities for a career in clinical pharmacology
Authors: N. Baber, M. J Brown, D. Webb
Journal: BMJ (1997)

Nigel Baber, Morris J Brown, and David Webb set out the pros and cons 

Clinical pharmacology or, more precisely, clinical pharmacology and therapeutics is a relatively young specialty concerned with the understanding of drug action in man, and with the practice of rational prescribing.

Clinical pharmacology was born out of pharmacology - drug action in animals and in in vitro systems and out of the explosion in the number of new drugs which were emerging about 20 years ago.

Three developments in particular have enabled the specialty to flourish and a fourth is responsible for current excitement.

Firstly, the recognition that clinical studies must be properly designed, executed, and analysed in order to be certain that observed drug effects are real and not due to chance, bias, or a placebo effect. In particular, the randomised, placebo controlled, or positive controlled double blind trial of sufficient size and power has been a mainstay of clinical pharmacology.

Secondly, the development of sensitive and specific assays of biological fluids by chromatography, and more recently by mass spectrometry, has enabled the detection of small quantities of parent drug and metabolises to be determined. This has enabled the subspecialty of pharmacokinetics - the study of the absorption, distribution, metabolism, and excretion of drugs to emerge.

Thirdly, the development of techniques to measure dynamic responses to drugs has allowed clinical pharmacologists to better define the dose effect or response relationship and to understand the mechanism of action of many important drugs. Some drugs can be used as tools or probes to understand physiological and pathophysiological processes, even if the drug itself never becomes a prescription medicine.

The fourth and most recent development is the interaction of molecular genetics and studies on the human genome with drug response and drug development. As we move into the era …
Treatment of Acute Heart Failure
Authors: Philip A. Poole-Wilson
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Short-term Evaluation of Synovectomy in Haemophilia
Authors: V. Pietrogrande, N. Dioguardi, P. M. Mannucci
Journal: BMJ (1972)

Twenty-three operations of synovectomy (15 on the knee, 5 on the ankle, and 3 on the elbow) were carried out over a three-year period in 19 patients with severe haemophilia A and B who were followed for an average period of 15 months postoperatively. Short-term evaluation of the results was mainly based on the postoperative incidence of haemarthrosis and on the range of joint motion, which were compared with the preoperative findings. Synovectomy reduced, but did not abolish, the occurrence of haemarthrosis; however, after the operation bleeding episodes were usually less severe and incapacitating. Joint mobility was often reduced despite an intensive and prolonged programme of physiotherapy. Nevertheless, most of the patients were pleased with the results of the operation as they could lead a more active life because of the decreased risk of joint bleeding. In the light of these findings we conclude that synovectomy is not the elective treatment of choice for haemophilic arthropathy. It may be indicated in a few selected cases when conservative treatment has failed to control repeated haemarthrosis and synovitis. Controlled clinical trials and long-term evaluation are needed to establish its effect on the final outcome of haemophilic arthropathy.
Epidemic Pleuritic Pain
Authors: J. Roche, F. G. Smiddy
Journal: BMJ (1946)

EPIDEMIC PLEURITIC PAINMED; CRAILT JOURNL 157 not lend itself to visual inspection.This may have been tem- porarily plugged with the stone, permitting the escape of bile as soon as it left its site of impaction.The effusion would in this case be first of all retroperitoneal, accounting for the fact that the initial pain during the abdominal crisis was clearly located to the back.The intra- peritoneal effusion would follow a secondary perforation through the peritoneum, as suggested by Buchanan (1918).It will be remembered that Cope (1925-6) described the peritoneum as appearing to " weep " bile.The obstruction to the biliary system was possibly not re- leased until after the initial escape of bile.After the relief of tension in the common duct the perforation would tend to close spontaneously.
White lines in the fingernails induced by combination chemotherapy.
Authors: M R Shetty
Journal: BMJ (1988)

Hypercarotenaemia in a tomato soup faddist A 24 year old woman presented with orange-yellow discoloration of her skin, most noticeable on her paLms and soles.Dietary assessment showed that her total daily intake of carotene was 9200 Rg, over half of which came from
Salbutamol-induced ketoacidosis.
Authors: D Leopold, A McEvoy
Journal: BMJ (1977)

ruling out the presence of bony secondaries, confirming the indication for primary surgical treatment.Whole-body bone scanning is easy to perform, non-invasive in nature, takes 30 minutes of the patient's time, and costs approximately £6.It should be routinely performed in the staging of carcinoma of the bronchus.
Tobacco advertising: A tricky business
Authors: F. Howell
Journal: BMJ (1993)

normal.Haemoglobin concentration was 85 g/l and the erythrocyte sedimentation rate was 30 mm in the first hour.Serum concentrations of electro- lytes, including calcium, were within normal limits, and angiotensin converting enzyme activity was normal.Results of tests for complement component (C3, C4), antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasm anti- bodies, and paraprotein were negative.A tuber- culin test also yielded negative results.Other investigations showed the presence of a malabsorption syndrome with steatorrhea.A jejunal biopsy specimen showed a pattern typical of Whipple's disease with the presence in the mucosa of numerous macrophages that were positive on periodic acid Schiff and Gram staining.Renal biopsy showed tubulointerstitial nephritis with many granulomatous formations; there was diffuse infiltration of interstitial cells and fibrosis with tubular degeneration.There was no central caseation, and no acid fast bacilli were seen on Ziehl-Neelsen staining.Immunofluorescence yielded unremarkable findings.Treatment with doxycycline was started.His diarrhoea resolved and his weight increased concurrently.His renal impairment, however, remained stable.Although Whipple's disease is a systemic con- dition that can cause granulomas in other organs, only one previous case of well documented granu- lomatous interstitial nephritis has been reported.2We believe that we ruled out other causes of granulomatous interstitial nephritis in our patient and that a link between the nephropathy and Whipple's disease is probable.Crohn's disease and Whipple's disease should probably be added to the list of aetiologic factors in granulomatous inter- stitial nephritis already cited.
Purpura on the rocks--with a twist
Authors: R. R. Siroty
Journal: JAMA (1976)

THE ENTITY of quinine-induced purpura is well recognized and has been described many times. On several occasions, its relation to the ingestion of cocktails mixed with quinine water—so-called cocktail purpura or gin-and-tonic purpura—has been reported. 1,2 We recently encountered a well-disguised case with potentially serious consequences.  Report of a Case  A 27-year-old woman was admitted to Dover General Hospital in January 1973 with chills and the rapid development of purpura, including buccal mucous membrane hemorrhages. Platelet count was 1,000/cu mm; other laboratory data were normal. The patient had had a recent episode of acute gastroenteritis but was otherwise well. She denied taking any drugs except a mixture of chlorpheniramine maleate, aspirin, and caffeine (Coricidin) and aspirin and denied drinking quinine-containing cocktails.  Bone-marrow examination revealed abundant numbers of normal-appearing megakaryocytes and normal myeloid and erythroid elements.  The patient was treated with prednisone (40 mg/day) and had a rapid and sustained rise
Adefovir dipivoxil (ADV) for the treatment of lamivudine resistant HBV (LAM-R) in post liver transplant (post-OLT) patients
Authors: E. Schiff, P. Neuhaus, H. Tillman, D. Samuel, N. Terrault, F. Durand, S. Xiong, N. Lama, C. James, J. Fry, H. Namini, C. Brosgart
Journal: Journal of Hepatology (2002)
Abrupt Postural Changes in Patients Undergoing Air Contrast Studies
Authors: Roy D. Wilson
Journal: JAMA (1966)

With the use of the Gracía-Oller axioencephalographic wheel 496 air contrast studies were performed. Of the patients studied 282 received general anesthesia. Twenty-three studies of the complete cardiovascular and respiratory effects of general anesthesia on these patients were performed, with the conclusion that the primary change observed was in total peripheral resistance. No deaths were related to the air studies or the anesthetic in the series. The Gracía-Oller axioencephalographic wheel and general anesthesia have been found to be safe for patients whenever there is doubt that an air study of diagnostic quality can be obtained otherwise.
Prevalence of sensitization to the predatory mite <i>Amblyseius cucumeris</i> as a new occupational allergen in horticulture
Authors: C. M. Giséle, M. D. Groenewoud, C. De G raaf in ′t Veld, A. J. Van Oorschot–van Nes, N. W. De J ong, A. M. Vermeulen, A. W. Van Toorenenbergen, A. Burdorf, H. De G root, R. G. Van Wijk
Journal: Allergy (2002)

Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyzeius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied.Four hundred and seventytwo employees were asked to fill in a questionnaire and were tested on location. Next to RAST, skin prick tests (SPTs) were performed with common inhalant allergens, the storage mite Tyrophagus putrescentiae (Tp) which serves as a temporary food source during the cultivation process and Ac. Furthermore, nasal challenge tests with Ac were carried out in 23 sensitized employees.SPTs positive to Ac were found in 109 employees (23%). Work-related symptoms were reported by 76.1%. Sensitization to Tp was found in 62 employees of whom 48 were also sensitized to Ac. Immunoglobulin (Ig)E-mediated allergy to inhalant allergens appeared to be an important risk factor for sensitization to Ac. Employees with rhinitis symptoms showed a significantly higher response to all Ac doses during the nasal challenge test compared with employees without rhinitis symptoms.The predatory mite Ac is a new occupational allergen in horticulture which can cause an IgE-mediated allergy in exposed employees. It is biologically active on the mucous membranes of the nose and therefore clinically relevant for the development of work-related symptoms.
Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors
Authors: Ylva Stewénius, Yuesheng Jin, Ingrid Øra, Jan de Kraker, Johannes Bras, Attila Frigyesi, Jan Alumets, Bengt Sandstedt, Alan K. Meeker, David Gisselsson
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In many childhood neoplasms, prognostic subgroups have been defined based on specific chromosome changes. In Wilms' tumor (WT), such subclassification has been hampered by the diverse and relatively unspecific pattern of chromosomal imbalances present in these tumors. Unspecific patterns of cytogenetic imbalances in tumors are often caused by mitotic segregation errors due to short dysfunctional telomeres. As an alternative to cytogenetic classification, we therefore have evaluated whether the rate of telomere-dependent chromosomal instability could influence the clinical course in WT patients. Experimental Design: Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from 41 WT patients. Results: Abnormal telomere shortening was found in cultured cells and in tissue sections from highly aggressive tumors. In vitro, dysfunctional telomeres were associated to specific cell division abnormalities, including anaphase bridges and multipolar mitoses. Assessment of mitotic figures in tissue sections revealed that anaphase bridges and multipolar mitoses were predominantly, but not exclusively, present in high-risk tumors and were predictors of poor event-free and overall survival. Conclusions: Telomere-dependent mitotic instability is present in a subgroup of WT, predominately consisting of high-risk tumors.
A double‐blind, placebo‐controlled study of house dust mite immunotherapy in Chinese asthmatic patients
Authors: H. Wang, X. Lin, C. Hao, C. Zhang, B. Sun, J. Zheng, P. Chen, J. Sheng, A. Wu, N. Zhong
Journal: Allergy (2005)

The purpose of this study was to determine if house dust mite immunotherapy with Alutard SQ is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma.This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6-45 years recruited from three different regions of Mainland China. Subjects were given a 52-week course of immunotherapy with Dermatophagoides pteronyssinus extract (Alutard Der p, ALK-Abelló, Hørsholm, Denmark) or placebo while their dose of inhaled corticosteroids (ICS) was maintained.129 subjects (64 in active group) completed the study. The symptom scores began to diverge at week 29 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.002) and medication (P = 0.007) scores during the second half of the treatment period. Both groups showed significant improvement in peak flow rate and bronchial hyperresponsiveness. Serum eosinophil cationic protein (ECP) also decreased in both groups of subjects, but peripheral blood eosinophil count remained unchanged. Skin test response decreased in actively treated subjects only, but Der p-specific immunoglobulin E (IgE) remained unchanged. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01).One year treatment with Alutard SQ house dust mite immunotherapy significantly reduced symptoms and medication use in asthmatic subjects. This was associated with a greater subjective improvement in asthma control.
Removable subcuticular skin suture in acute appendicitis: a prospective comparative clinical trial.
Authors: G B Hopkinson, B R Bullen
Journal: BMJ (1982)

Removable subcuticular skin suture in acute appendicitis: a prospective comparative clinical trial Standard surgical teaching advises the use of interrupted sutures for skin closure in potentially infected wounds.'-3Trials supporting or refuting this premise are few.So far as we are aware no trial has been performed using a removable subcuticular stitch for skin closure in acute appendicitis.We report the results of a prospective trial to compare the two methods of skin closure.
A Successful Case of Trephining for Epilepsy, with Subsequent Resection of Trephine Opening
Authors: None Williamson, R. Jones
Journal: BMJ (1889)

this course would be prejudicial to the patient.Otherwise the patient can, within seven days, exercise this right; and the fresh justice is to see the patient and report to the Commissioners, thus reopening the whole question of his insanity, disturbingly, in the mind of the lunatic, and placing the certifying medical men in a position liable to misunderstanding and unduly vulnerable.A constable, relieving officer, or overseer of a parish, knowing of a non-pauper and non-wandering alleged lunatic, but one who is not under proper care and control, or who is cruelly treated or neglected by those in charge of him, shall, on oath, inform the justice specially appointed under the new Act, who may visit the alleged lunatic if he thinks well to do so, and, whether he visit him or not, shall direct two medical men to visit him and certify their opinion as to his mental state; and the justice, if satisfied that the alleged lunatic is a proper person to be placed under care, may order his removal to an asylum, etc., or may detain him and suspend execution of the order of removal for fourteen days, or may allow a friend to take care of him.But the removal cannot take place in opposition to a medical certificate of unfitness of the alleged lunatic for removal.The reception order holds good for fourteen days, or, if its execution is suspended by a medical certifi- cate, as just stated, it becomes renewed in effect for three days after a reversing medical certificate of fitness for removal has been obtained.The certificates accompanying the reception order under which patients are to be received under care are not to be signed by per- sons in any way interested in the payment to be made for these patients, or by the near relatives of such persons.Neither of the persons signing the medical certificates in sup- port of a petition for a reception order shall be the father or father-in-law, mother or mother-in-law, son or son-in-law, daughter
Four rules for the reinvention of health care
Authors: Enrico Coiera
Journal: BMJ (2004)

If health care is to evolve at a pace that will meet the needs of society it will need to embrace this science of sociotechnical design, but ultimately it is our culture's beliefs and values that shape what we will create and what we dream 

Futurists might like to speculate on what the health services of 2020 look like. The world may be such that as a clinician you work in flexible virtual teams and some of your colleagues are computers. You would of course instinctively mistrust clinicians who always know the answer without consulting the information grid, and patients often choose to be the team leader. Keyboards are banned as harmful and can be found in museums, next to punch cards and spittoons. The health record is a direct multimedia history of conversations, and a software agent is its curator. For the still cognitively limited clinician, your earring whispers your patient's name when you meet.

More importantly, in 2020 the health system in most nations will have to treat proportionately more people, with more illness, using relatively fewer tax dollars and workers.1 Given that commentators today are alarmed at the current strains on the health system, we have to assume that by 2020 the healthcare systems in most nations will therefore either have somehow transformed substantially or will have failed. If health care is to flourish in the coming setting of diminished resources and increased demand, then it will do so because we have explicitly designed and implemented new systems of care that are fundamentally sustainable. Given the likely enormity of that task, it may require nothing less than the reinvention of health care.

Many of the innovations needed for this reinvention are still unimagined today, but we can predict some of what must come to pass. In …
Art From the Mentally Disturbed: The Shattered Vision of Schizophrenics
Authors: John R. Curtis
Journal: JAMA (1966)

The artistic efforts of patients with emotional disturbances represent a subject of considerable fascination to many people. This interest seems to range from morbid curiosity and pseudopsychological wonder at one extreme to the search for insight and valuable scientific knowledge on the other. The author of this book, Dr. Plokker, Professor of Psychiatry at the University of Utrecht, is in an unusually good position to discuss patient art, for he is both a painter and a psychiatrist. Unfortunately, however, Dr. Plokker does not combine his talents in this book. Instead, in the first 130 pages of the book he propounds with some repetition various psychiatric, philosophical, and psychological theories about schizophrenia. His descriptions are colorful and at times, in spite of the cumbersome translation from the Dutch, vivid. It should be noted, however, that the thinking of European psychiatrists regarding schizophrenia is somewhat different from that of American psychiatrists. The
Ectopic Lymphoid-Organ Development Occurs through Interleukin 7-Mediated Enhanced Survival of Lymphoid-Tissue-Inducer Cells
Authors: Dominik Meier, Caroline Bornmann, Stephane Chappaz, Sandrine Schmutz, Luc A. Otten, Rhodri Ceredig, Hans Acha-Orbea, Daniela Finke
Journal: Immunity (2007)
Estrogens and menopause
Authors: C. M. Proudfit
Journal: JAMA (1976)

Recent reports suggest that the administration of estrogens to postmenopausal women is associated with an increased risk of developing endometrial cancer. Although the evidence is indirect, it is consistent with the recent introduction into the population of a carcinogen whose primary effect is on the endometrium. Estrogens have often been prescribed for trivial reasons and have been taken for long periods. The median reported length of estrogen use has been 10 years. There is a latency period in the carcinogenic effect so a more frequent incidence of endometrial carcinoma may yet follow. In the meantime, use of estrogens for specific menopausal symptoms is justified. There is less concern in prescribing estrogens for hysterectomized patients. Most emotional problems are better handled by counseling or short-term use of sedatives or tranquilizers. Senile osteoporosis may be benefited by estrogen therapy. Following oophorectomy early in life estrogen treatment may retard onset of osteoporosis but cannot reverse the aging process. Cyclic administration of estrogen use is advised with the lowest effective dose. Vasomotor symptoms require temporary treatment but atrophic vaginitis needs longer therapy. Reevaluation of patients at 6-month intervals at first and then yearly is recommended. A Papanicolaou smear should include material from the endometrial canal. Abnormal bleeding requires investigation. The patient should be informed regarding risks and benefits of estrogen therapy.
Somatic mutations in acute promyelocytic leukemia (APL) identified by exome sequencing
Authors: P A Greif, M Yaghmaie, N P Konstandin, B Ksienzyk, K Alimoghaddam, A Ghavamzadeh, A Hauser, A Graf, S Krebs, H Blum, S K Bohlander
Journal: Leukemia (2011)