tbuckley/cabot-search huggingface dataset:
Physical Fitness as a Predictor of Cardiovascular Mortality in Asymptomatic North American Men
Authors: Lars-Göran Ekelund, William L. Haskell, Jeffrey L. Johnson, Fredrick S. Whaley, Michael H. Criqui, David S. Sheps
Journal: New England Journal of Medicine (1988)

Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. The heart rate during submaximal exercise (stage 2 of the exercise test) and the duration of exercise were used as measures of physical fitness. Men with incomplete data (n = 308) or who were using cardiovascular drugs (n = 213) were excluded from the analysis. Men who had clinical evidence of cardiovascular disease at base line (n = 649) were analyzed separately. Forty-five deaths from cardiovascular causes occurred among the remaining 3106 men. A lower level of physical fitness was associated with a higher risk of death from cardiovascular and coronary heart disease, after adjustment for age and cardiovascular risk factors. The relative risk of death from cardiovascular causes was 2.7 (95 percent confidence interval, 1.4 to 5.1; P = 0.003) for healthy men with an increment of 35 beats per minute in the heart rate during stage 2, and 3.0 (95 percent confidence interval, 1.6 to 5.5; P = 0.0004) for those with a decrement of 4.4 minutes in the exercise time spent on the treadmill. The corresponding values for death from coronary heart disease were 3.2 (95 percent confidence interval, 1.5 to 6.7; P = 0.003) and 2.8 (95 percent confidence interval, 1.3 to 6.1; P = 0.007), respectively. We conclude that a lower level of physical fitness is associated with a higher risk of death from coronary heart disease and cardiovascular disease in clinically healthy men, independent of conventional coronary risk factors. (N Engl J Med 1988; 319:1379–84.)
Cyclospora Species -- A New Protozoan Pathogen of Humans
Authors: Ynes R. Ortega, Charles R. Sterling, Robert H. Gilman, Vitaliano A. Cama, Fernando Diaz
Journal: New England Journal of Medicine (1993)

Organisms referred to as "cyanobacterium-like bodies" have now been identified worldwide in the feces of both immunocompetent and immunocompromised patients with diarrhea. Organisms with a similar appearance have been isolated from Peruvian patients since 1985. From 1988 to 1991 we studied prospectively two cohorts of infants and young children infected with this organism. We now attempt to identify it.
HMOs and Physicians without Board Certification
Authors: Asha P. Wallace
Journal: New England Journal of Medicine (1993)

To the Editor: The practice by health maintenance organizations (HMOs) of demanding board certification of participating physicians has become an important factor influencing access to health care in Massachusetts and the rest of the United States. When managed care first appeared, HMOs enlisted physicians and then used these rosters to market their plans. Concurrently, they developed credentialing criteria, which typically included information on training and licensure, board certification, and malpractice experience. Then HMOs began to emphasize in their marketing that they had only board-certified physicians on their panels, implying that this restriction defined a better plan. As managed care has . . .
Synthesis and Secretion of Insulin-like Growth Factor II by a Leiomyosarcoma with Associated Hypoglycemia
Authors: William H. Daughaday, Mary Ann Emanuele, Marion H. Brooks, Anthony L. Barbato, Milan Kapadia, Peter Rotwein
Journal: New England Journal of Medicine (1988)

We describe a case of recurrent hypoglycemia apparently caused by secretion of insulin-like growth factor II (IGF-II) by a leiomyosarcoma. A 67-year-old woman presented with recurrent severe hypoglycemia and a large mass in the thorax. During hypoglycemia, plasma cortisol was elevated, but insulin and growth hormone levels were low. After resection of a large leiomyosarcoma, the hypoglycemia resolved. After an eight-year remission, both the tumor and symptomatic hypoglycemia recurred. During a second operation a second large tumor was removed, with relief of the patient's hypoglycemia. The tumor contained high concentrations of IGF-II mRNA and 2100 ng of IGF-II immunoreactive peptide per gram. Filtration through a BioGel P-60 gel column established that 77 percent of the IGF-II was present as a larger molecule, demonstrating incomplete processing of the pro-IGF-II peptides. A similar fraction of high-molecular-weight IGF-II was present in the serum, indicating that the tumor was the chief source of IGF-II. The high-molecular-weight IGF-II found in both the tumor and serum was fully reactive with the IGF-II receptor. Radioimmunoassay showed that the concentrations of insulin-like growth factor I (IGF-I) in tumor and serum were low, suggesting feedback inhibition of growth hormone secretion by IGF-II. Eight months after reoperation, plasma concentrations of IGF-I and IGF-II were normal, and high-molecular-weight IGF-II was virtually undetectable. We conclude that the most likely cause of this patient's recurrent hypoglycemia was IGF-II produced by the leiomyosarcoma. (N Engl J Med 1988; 319:1434–40.)
The Impact Of The Establishment Of a Hematology Telemedicine Consult Service In a Referral Center On Patients’ Travel Distance, Travel Cost and Satisfaction Scores
Authors: Sarvari Venkata Yellapragada, Jesus Hermosillo-Rodriguez, Yvonne Sada, Annette Walder, Kathy Sam, Alka Mulchandani, Teresa G Hayes, Davila A Jessica
Journal: Blood (2013)
The 57 club
Authors: James Owen Drife
Journal: BMJ (2004)

I rarely feel moved to turn my birthday into a public celebration. That might have been a problem if I had been Queen, but as things are it has been easy to let my 30th, 40th, and 50th birthdays sidle past with some bubbly and a family meal. Soon my 57th will do the same.

Fifty-seven is a special age for male doctors. With statutory retirement at 65 we are into the last eight, in Olympic phraseology.

It is …
Decreased gene dosage of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice
Authors: Dipankar Ray, Yasuhisa Terao, Li-Hao Chu, Suchitra Prasad, Xianghong Zou, Roberta Franks, Konstantin Christov, Hiroaki Kiyokawa
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2584 

The Cdk-activating Cdc25A phosphatase is overexpressed in various cancers including breast cancer. Cdc25A downregulation is critical for S-phase checkpoint, and Cdc25A overexpression could promote not only aberrant proliferation but also survival with chromosomal instability. While Cdc25A has been suggested to be an oncogene, it has not been examined how genetic manipulations to suppress Cdc25A expression affect carcinogenesis. To determine the impact of Cdc25A downregulation, we generated Cdc25A-null mice by gene targeting. Cdc25A−/− mice died in utero during the peri-implantation period (E4.5-7.5). Cdc25A+/− mice showed no appreciable developmental defect, with normal fertility and nursing. However, Cdc25A+/− mice displayed marked resistance to tumorigenesis induced by MMTV -driven oncogenes. After crossbreeding, all MMTV-ras transgenic mice in the Cdc25A +/+ background developed mammary tumors with latency of 20 weeks. In contrast, 50% of MMTV-ras mice in the Cdc25A +/− background did not display detectable tumors during 24-month observation. The neu oncogene functions upstream of ras in mammary carcinogenesis. MMTV-neu mice in the Cdc25A +/+ background developed tumors with latency of 25 weeks, while tumor latency in MMTV-neu; Cdc25A +/− mice was prolonged to 34 weeks. The tumor suppressive effect of Cdc25A heterozygosity was consistent with decreased potential of Cdc25A +/− mouse embryonic fibroblasts (MEFs) to undergo transformation. Cdc25A +/− MEFs proliferated normally, but exhibited significantly decreased colony formation in soft agar following retroviral expression of H-rasV12 plus c-myc or a dominant negative (DN) p53 mutant. Consistently, suppression of Cdc25A expression was inhibitory on transformation of MCF-10A human non-transformed mammary epithelial cells. Lentiviruses encoding two distinct anti-Cdc25A short hairpin RNAs decreased Cdc25A levels in MCF-10A cells by 30% and 60%, respectively, which was correlated with inhibition of colony formation after transduction with H-rasV12 plus c-myc or DNp53. However, lowering Cdc25A levels after expression of the oncogenes was not inhibitory on colony formation, suggesting the importance of Cdc25A at initial phases of transformation. We are investigating impacts of Cdc25A downregulation on pathways controlling checkpoint and carcinogenesis, using genomics/proteomics. These studies provide evidence that Cdc25A is a rate-limiting oncogene for mammary carcinogenesis, and recapitulate that Cdc25 is a promising therapeutic target. This work is supported in part by NIH grants, CA100204 and HD38085, and a DOD grant, DAMD17-02-1-0413.
The New Era of Informed Consent
Authors: Erica S. Spatz, Harlan M. Krumholz, Benjamin W. Moulton
Journal: JAMA (2016)

The rights of patients tobeinformedaboutcaredecisions in clinical practice is yet again under scrutiny, both in the United States and around the world.The well-ingrained ethical-legal process of informed consent, so fundamental to patient autonomy-or the patient's right to selfdetermination-was the subject of a 2015 UK Supreme Court case (Montgomery v Lanarkshire Health Board). 1 In that case, a woman with insulin-dependent diabetes, claimedthatherobstetricianfailedtocommunicatetherisk of shoulder dystocia during vaginal delivery (a complication associated with fetal macrosomia) that ultimately resultedinseverefetalbrainanoxia.Sheclaimedthathadshe received full information about the risks, she would have opted for a cesarean delivery.Yet the treating obstetrician (andotherexpertphysicianscalledtotrial)claimedthatthe ensuing risk was very small and thus appropriately not communicated because a cesarean delivery is not in the maternal interest.The obstetrician reported that "…had I raised it [the risks of shoulder dystocia] with her then yes, she would have no doubt requested a caesarean section, as would any diabetic today." 1 In its final decision, the UK Supreme Court ruled that the standard for what physicians should inform patients about the risks, benefits, and alternatives of treatment will no longer be determined by what a responsible body of physicians deems important but rather by what a reasonable patient deems important.In rendering this decision, the court swept away decades of medical paternalism in the United Kingdom to embrace a new patient-centered standard.Perhaps more compelling, the head of the Royal College of Surgeons urged that the only way to operationalize such a substantial and needed change is through shared decision making, a collaborative communication processbetweencliniciansandpatientsthatintegratesthe best evidence available with the patients' values and preferences, to promote high-quality health care decisions.The UK law is not unprecedented.In the United States, approximately half of the states have adopted the reasonable-patient standard.The reasonable-patient standard views the informed consent communication process from the patient's perspective.It requires physicians and other health care practitioners to disclose all relevant information about the risks, benefits, and alternatives of a proposed treatment that an objective patient would find material in making an intelligent decision as to whether to agree to the proposed procedure. 2Even in those states that apply the reasonable-patient standard, however, the informed consent process is often ill-configured to meet patients' informational needs.Informed consent discussions are often devoid of detailsaboutthematerialrisks,benefits,andalternativesthat
Polycythemia Vera in an Eleven-Year-Old Girl
Authors: Arthur A. Marlow, Virgil F. Fairbanks
Journal: New England Journal of Medicine (1960)

WINTROBE1 has reported that cases of polycythemia vera have been described early in life, but evidence that they are not examples of secondary polycythemia has seldom been presented. He states that the case described by Halbertsma2 , 3 in a six-year-old boy is the most convincing report. Lawrence4 refers to 1 well documented case of polycythemia vera in a girl aged nine years and nine months. Because of the paucity of reports of polycythemia vera in childhood studied by methods available today, the following case is reported.Case ReportA Caucasian girl was born in Maracaibo, Venezuela (sea level), on December 14, . . .
CBIO-13CO-DELIVERY OF EGFR AND HSV-tk BY LCMV-PSEUDOTYPED BICISTRONIC LENTIVIRAL VECTORS TO ENHANCE THERAPEUTIC GENE DISTRIBUTION FOR GLIOBLASTOMA TREATMENT
Authors: Jubayer Al Hossain, Hrvoje Miletic, Kristoffer Riecken, Boris Fehse
Journal: Neuro-Oncology (2015)

Malignant gliomas, the largest group of primary intracerebrial tumors, are one of the most-difficult-to-cure cancers. The outcome has not significantly improved in recent years, despite considerable advances in our understanding of the molecular pathogenesis and improvement of surgical techniques, radio- and chemo-therapy. For glioblastoma multiforme (GBM), the most malignant form of glioma, the median survival time is approximately 15 months after diagnosis. Although complete remission of experimental GBM on MRI has been reported by using a lentiviral vector based suicide gene therapy approach1, recurrence of tumors at distant sites is common which is mainly caused by invasive glioma cells that escape treatment. Thus, a better distribution of the suicide gene is needed in order to target and efficiently kill the infiltrative glioma cells to prolong recurrence-free time span and improve the therapeutic effect. By introducing EGFR, a gene that has been reported to promote invasion of glioma cells2 into our LCMV-pseudotyped lentiviral vector system, we want to enhance the distribution of the suicide gene HSV-TK. This might lead to a more efficient killing of glioma cells in both tumor core and invasive areas.
Passion required
Authors: Liam Farrell
Journal: BMJ (2008)

A few years ago I felt compelled (out of both a sense of duty and a feeling of nausea) to chide the Independent about its complementary health guru. “Oooh, but he’s very popular,” was the newspaper’s defence. So is pornography, I said. “Oooh no,” they replied, in an outraged tone, “that wouldn’t be ethical,” though I reckoned that big tits on page 3 is a lot more ethical than snake oil salesmen peddling the illusion of knowledge to the gullible and the vulnerable.

But if even a newspaper as pretentious and worthily dull as the Independent can be trying to court the favour of the lumpen proletariat, then there is a lesson for all of us.

Every quarter someone (I don’t know who, some anonymous benefactor who thinks I should be bettering myself) sends me the Drug and Therapeutics Bulletin. As I am sometimes a good doctor, I read it, though I usually skip straight through to the conclusion. I suppose this is cheating, but it’s not an inviting read.

Its very appearance bespeaks gravity and austerity: no photographs, no colour, no poetic exaggeration, no leavening of humour, no swallow’s flight of whimsy. If it had been required reading for the Spartan children on their overnight ordeal on the mountain, most of them would have reneged and headed for Lesbos to chill out and smoke lotus petals. It is unfailingly cold and logical, the Mr Spock of medical journals, half human, half Vulcan.

Even the conclusion is tough going: dry and academic, every objective assessment cogently and impeccably argued, but I do wish for a bit more passion, more Bones McCoy than Mr Spock. We are not robots, not automatons, and we respond to the heart as well as the head; “the best lack all conviction, while the worst are full of passionate intensity,” said Yeats, but why should we cede the passionate intensity to the charlatans? We need ferocity, we need the rage to win, we need the rough beast.

If the Drug and Therapeutics Bulletin is right, and it always is, its message should be throbbing with righteous wrath, and appeal to the emotion as well as the intellect. I’m thinking something like “Mandy is 22, enjoys dancing, shopping and dwarf-smuggling, and wants to work for world peace and marry a footballer.

“And she thinks that this new non-steroidal anti-inflammatory is shit.”
Case 31-2005
Authors: Jonathan Kay, Robert T. McCluskey
Journal: New England Journal of Medicine (2005)

A 60-year-old man was evaluated at the hospital because of renal failure. He had been well until a trip to Colorado three months earlier; one week after returning he reported fatigue, edema, and a rash on his arms and legs. Laboratory evaluation revealed anemia, renal insufficiency, microscopic hematuria, and proteinuria. Serum complement levels were decreased. A skin biopsy showed leukocytoclastic vasculitis. Testing for cryoglobulins and antineutrophil cytoplasmic antibodies was negative. A diagnostic procedure was performed.
Toxic Effects of Phenylbutazone
Authors: J. C. Leonard
Journal: BMJ (1953)

Toxic side-reactions severe enough to necessitate stopping the drug occurred in 46 patients.The following reactions, usually in various combinations, were noted: (1) Twenty- one patients noticed severe anorexia and upper abdominal pain, one of these also having looseness of the bowels.(2) Seventeen complained of dryness of the mouth and throat, and were found to have redness of the anterior faucial pillars and uvula.Two of these had actual ulcera- tion, which in one caused a submaxillary abscess requir- ing surgical drainage.Blood counts remained normal in this group.(3) Sixteen developed punctate erythematous rashes.(4) Two had enlargement of the glands in the posterior triangles of the neck.( 5) One patient suffered from severe vertigo.(6) One developed granulopenia, recovering after the drug was withheld; white blood count 1,700, neutrophils 39%.The white count before treat- ment was 12,000, neutrophils 79%.Several patients showed a transient eosinophilia.( 7) Three patients had exacerba- tions of the rheumatoid lesions of their hands.Sodium retention was thought to be responsible for the slight gain in weight noticed in most patients, but only two developed pronounced oedema.This disappeared in one after salt restriction, which had not been carried out as requested, but persisted despite these measures in the other.Response to Phenylbutazone Compared with Toxic Reactions Response No. No. of Toxic Reactions Noted In All Patients Treated Complete symptomatic relief 31159 1926 Marked .1 28 f Analgesic effect, similar to aspirin .. 15 7 No symptomatic relief .. .. 25 3Drug not given long enough to observe therapeutic effect . . . . . . .
P32 Role of non acid and proximal reflux in scleroderma-associated interstitial lung disease
Authors: A De Lauretis, S Ward, C Murray, C Clayman, V Ong, C Denton, A Bikov, D Visca, G Lindahl, A Chetta, M Aiello, W Wuyts, M Kreuter, T Maher, C Stock, AU Wells, E Renzoni
Journal: Thorax (2015)

<h3>Background</h3> Oesophageal involvement is extremely common in patients with scleroderma. This prospective observational study (NCT02136394) addresses the relationship between gastro-oesophageal reflux (GORD) and scleroderma-associated interstitial lung disease (SSc-ILD), and evaluates the clinical utility of noninvasive tests of microaspiration. <h3>Materials and methods</h3> We present preliminary results of the first 27 enrolled patients (median age 59 [min/max 35/79], median FVC = 74% [38/128%], median DLCO = 39% [21/72%], female 70%, diffuse SSc 33%). Collected clinical data included 24 hr impedance (carried out off PPI), respiratory (K-BILD and Leicester cough questionnaires) and GORD symptom questionnaires (UCLA SCTC GIT 2.0 Questionnaire, Reflux Disease Questionnaire RDQ), as well as full lung function test data. Pepsin levels were measured in saliva in all patients, and in a subset of 6 patients in bronchoalveolar lavage (BAL). <h3>Results</h3> Non acid reflux and proximal reflux were detected in 54% and 49% of patients, respectively. In the subgroup of patients with normal DeMeester score (i.e. global impedance index of acid exposure), 66% had non acid reflux episodes. The DeMeester score (median 14.2 [min/max 0.8/156]) was correlated with total scores GORD questionnaire scores (e.g. RDQ, r = 0.68 p = 0.003; GIT 2.0, r = 0.68 p = 0.004), but not with K-BILD, Leicester questionnaire, or saliva pepsin. Proximal reflux episodes were moderately correlated with the Leicester total score (r = -0.76 p = 0.002) and with saliva pepsin (r = 0.46 p = 0.05). Saliva pepsin (median concentration 2.34 ng/ml [2.34/12.4]) was correlated with the impedance cough index association (r = 0.53, p = 0.02). BAL pepsin was present in all six cases (median concentration 2.34 ng/ml [2.34/12.4]) and was correlated with FVC (r = -0.8, p = 0.04). Lung function test parameters were not correlated with saliva pepsin, but were significantly, if loosely, correlated with impedance measures of acid exposure in the recumbent position (e.g.% time of exposure, r = -0.43 p = 0.04). <h3>Conclusions</h3> Proximal and non acid reflux are highly prevalent in the SSc-ILD population and are associated with a high symptom burden. Pepsin is measurable in BAL of SSc-ILD patients and suggests microaspiration into the lungs, although larger numbers are needed to confirm these findings and define whether saliva pepsin measurement could represent a useful non invasive marker of microaspiration.
Case 52-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, P.R. Skolnik, S.M. de la Monte
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 31-year-old woman was admitted to the hospital because of headache, altered mental status, and dysarthria.The patient was well until seven years earlier, when squamous-cell carcinoma of the cervix, Stage IB, was found. A radical hysterectomy with pelvic lymph-node dissection was performed at this hospital, with the transfusion of one unit of packed red cells. Pathological examination showed invasive large-cell, nonkeratinizing squamous-cell carcinoma with extensive lymphatic invasion, but the pelvic lymph nodes and all resection margins were free of disease. Radiation treatment was administered to the pelvis. Estrogenic hormone was prescribed, and the patient recovered uneventfully. . . .
Risk Factors Associated with Nasopharyngeal Carcinoma
Authors: Brian E. Henderson, Emma Louie, Jennie SooHoo Jing, Phillip Buell, Murray B. Gardner
Journal: New England Journal of Medicine (1976)

We performed a case-control study of nasopharyngeal squamous-cell carcinoma to identify risk factors associated with the disease. Interviews with 156 patients and 267 controls revealed that increased risk was significantly associated with a prior history of ear, nose or throat disease (relative risk = 1.8, P = 0.006) and occupational exposure to fumes (relative risk = 2.0, P = 0.006), smoke (relative risk = 3.0, P = 0.008) and chemicals (relative risk = 2.4, P = 0.006). Among Chinese, other Asians and Mexican-Americans, increased risk was also associated with foreign birthplace (relative risk = 2.1, P = 0.04), probably reflecting childhood exposure to carcinogens in inhaled smoke. In Chinese patients the risk associated with foreign birthplace and occupational exposure increased among those with HLA-A2 and less than two antigens at the B locus, suggesting a genetic variation in susceptibility.