tbuckley/cabot-search huggingface dataset:
Incidence of insulin dependent diabetes in children aged under 15 years in the British Isles during 1988.
Authors: M A Metcalfe, J D Baum
Journal: BMJ (1991)

OBJECTIVE--To ascertain the annual incidence rate of insulin dependent diabetes diagnosed in children under the age of 15 years in the British Isles during 1988, and to compare the results with an earlier study carried out in 1973-4. DESIGN--Active monthly reporting of cases by consultant paediatricians, with additional input from diabetologists and all specialist diabetes nurses and health visitors. SETTING--British Isles (England, Wales, Scotland, Northern Ireland, Republic of Ireland) with a total population at risk of 11,819,000 children. PATIENTS--All children diagnosed under the age of 15 years with primary insulin dependent diabetes from 1 January to 31 December 1988 and resident in the British Isles at diagnosis. MAIN OUTCOME MEASURES--National incidence rate of insulin dependent diabetes; differences in incidence rates between regions and between three age groups: 4 and under, 5-9, and 10-14 year olds. RESULTS--1600 children (837 boys and 763 girls) had a confirmed diagnosis of insulin dependent diabetes, giving a national incidence rate of 13.5/100,000/year (95% confidence interval 12.9 to 14.2/100,000/year). This was considerably higher than the incidence rate of 7.7/100,000/year in children under the age of 16 years reported in the British Diabetic Association9s study of 1973-4. The age-sex adjusted rates varied between regions, ranging from 6.8/100,000/year (Republic of Ireland) to 19.8/100,000/year (Scotland). There were considerable differences in the numbers of cases diagnosed each month, with the 10-14 year age group showing the most seasonal variation. A quarter of the children (404/1600) were under 5 years old. Case ascertainment was estimated as 90%. CONCLUSIONS--Insulin dependent diabetes in the British Isles does not seem to occur uniformly over time or geographical area. Even allowing for differences in ascertainment between the 1973-4 and 1988 studies, there seems to have been an increase in the incidence rate of insulin dependent diabetes in children under the age of 15 years during the 15 year time period. If diabetes is becoming more common in this age group, possibly by developing earlier in susceptible children, this would be a matter of considerable public health concern.
Improve environment to reduce pressure to prescribe antipsychotic drugs in nursing homes
Authors: P. Whitby
Journal: BMJ (2012)

McCleery and Fox say that the ethical concern about prescribing antipsychotic drugs to residents of nursing homes who have dementia is worthy of an editorial in itself.1 Rarely do such patients ask to be treated: requests usually come from care staff. However, such requests do not result simply from a desire for a quiet life for …
Case 7-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Robert Klein, Stanley J. Robboy
Journal: New England Journal of Medicine (1973)

Presentation of CaseA newborn girl, aged eight hours, was admitted to the hospital because of petechiae.The child was the product of a 39-week gestation in a gravida 2, 23-year-old mother. The pregnancy was complicated by a febrile illness without a rash at three months and by diarrhea on several occasions in the final trimester. The child's mother gave a history of rubella in. childhood; her blood group was A, Rh positive; a serologic test for syphilis was negative. The Apgar score at birth was 8 on a scale of 10, and the birth weight was 1.8 kg. There . . .
Abstract 5379: Mechanism of fludarabine and oxaliplatin combined activity depends on the activity of XPF endonuclease
Authors: Alma Zecevic, Brett Ewald, Deepa Sampath, William Wierda, William Plunkett
Journal: Cancer Research (2010)

Abstract We set out to determine the mechanism by which fludarabine and oxaliplatin exert more than additive cell killing in chronic lymphocytic leukemia (CLL). We postulate that enhanced activity of oxaliplatin and fludarabine combination is based on termination by fludarabine of DNA re-synthesis associated with nucleotide excision repair (NER) following removal of oxaliplatin adducts. The blocked repair would result in single-strand and double-strand DNA breaks which would activate cell DNA damage signaling and apoptosis. More than additive apoptotic killing was observed in 49% (±22) of CLL cells after exposure to oxaliplatin and fludarabine in vitro, although single agents showed minimal increase in cell death (3% ±9 for oxaliplatin, 13% ±14 for fludarabine), as demonstrated by Annexin V and PI staining at 24 hr (expected vs. observed p=0.0003; n=10). Oxaliplatin induced a 2-fold increase in DNA synthesis in CLL cells, which was inhibited by fludarabine, as determined by thymidine incorporation (n=5). Knockdown of XPF, the NER 5′ endonuclease, in CLL patient samples (n=3) eliminated oxaliplatin induced DNA synthesis (3-fold increase in thymidine incorporation with scramble siRNA compared to 1.4-fold increase with XPF siRNA). Wild type CHO (AA8) cells showed more than additive killing after combination treatment similar to the observation with CLL patient samples (predicted survival 50%; observed 21%). In contrast, only additive killing was observed in CHO cells lacking XPF (UV41) with equitoxic doses of oxaliplatin and fludarabine (predicted survival 56%; observed 54%) suggesting that XPF function is essential for the cooperative interaction of the combination. Alkaline assays demonstrated that inhibition of repair by fludarabine was accompanied by DNA strand break formation within 12 hr (n=4) in CLL patients samples. The increase in Olive tail moment ranged from 2- to 5-fold, confirming induction of single-strand breaks. The double-strand break repair proteins ATM, SMC1, H2AX and DNA-PKcs were phosphorylated as early as 2 hr post-treatment with the combination and persisted up to 24 hr (3-fold, 24-fold, 10-fold and 10-fold increase, respectively; n=4). This response suggests that DNA damage generated by fludarabine and oxaliplatin exposure was processed to double-strand DNA breaks in CLL cells. Our work provides evidence that the combination of oxaliplatin and fludarabine results in the formation of toxic DNA damage and that their combined activity depends on a functional NER pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5379.
Ultrasonography, Cholelithiasis, and Sickle Cell Disease
Authors: Richard W. Holt
Journal: JAMA (1978)

To the Editor.—  Kappelman and Sanders (239:1426, 1978) call attention to the role of ultrasonography in the evaluation of gallbladder disease. We concur with their recommendations and wish to note additional clinical situations in which this diagnostic modality is advisable.  While cholelithiasis is uncommon in the pediatric population, we have used ultrasound to diagnose cholelithiasis in children. 1 The absence of ionizing radiation makes this procedure particularly attractive in this age group.  We have recently diagnosed cholelithiasis in two adult patients with sickle cell disease and suspected acute cholecystitis. The abdominal crisis of sickle cell disease is often difficult to distinguish from gallbladder disease. Oral cholecystograms and intravenous cholangiograms are often not possible because of jaundice. We recommend that patients with sickle cell disease and in particular those with abdominal pain undergo cholecystosonography to establish the presence or absence of gallstones.
James Arscott Raleigh Bickford
Authors: J. Cox, P. Fisher
Journal: BMJ (2009)

Born in Tavistock in 1917, son of Dr Bertram Bickford DSO, naval surgeon, James Arscott Raleigh Bickford grew up in North Devon. Educated at Probus Prep School in Cornwall and Epsom College in Surrey, he went to medical school at St Bartholomew’s Hospital, London. Qualifying in 1941, he became surgeon lieutenant in the Royal Navy (1942-5), serving on board the destroyer HMS Goathland . He was on the Aorangi (requisitioned as a hospital ship) on D Day.

Advised by his father after demobilisation to choose what was not popular, he went to Bodmin Mental Hospital in 1946. Working there and walking over the moors he loved helped to formulate his approach to psychiatric care. Two psychiatric registrar posts followed, one at …
A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma
Authors: Geoffrey L. Chupp, Chun Geun Lee, Nizar Jarjour, Yun Michael Shim, Carole T. Holm, Susan He, James D. Dziura, Jennifer Reed, Anthony J. Coyle, Peter Kiener, Mark Cullen, Martine Grandsaigne, Marie-Christine Dombret, Michel Aubier, Marina Pretolani, Jack A. Elias
Journal: New England Journal of Medicine (2007)

The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.We quantified serum YKL-40 levels in three cohorts of patients with asthma--one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin--as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.
Small bowel haemorrhage due to cytomegalovirus vasculitis.
Authors: J M Sackier, S B Kelly, D Clarke, A J Rees, C B Wood
Journal: Gut (1991)

<b>Background:</b> Joint immobilisation improves the therapeutic effect of intra-articular glucocorticoid injection for knee synovitis. This may be due to retarded steroid resorption by immobilisation, a procedure that also could influence cartilage and bone metabolism. <b>Objective:</b> To evaluate changes in cartilage and bone turnover after intra-articular glucocorticoid treatment for knee synovitis with and without postinjection rest. <b>Methods:</b> 20 patients with rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to normal activity after intra-articular glucocorticoid treatment. Serum and urine markers of cartilage and bone turnover were studied for two weeks. Cartilage oligomeric matrix protein (COMP) was used as a marker of cartilage turnover, osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of bone resorption. <b>Results:</b> After the glucocorticoid injection COMP levels decreased in both groups (p&lt;0.001), but significantly more in resting patients. Serum osteocalcin levels decreased significantly (p&lt;0.001) without any difference between the groups. DPD was unchanged in both groups. <b>Conclusions:</b> Intra-articular glucocorticoid treatment for knee synovitis reduced serum COMP, which suggests that such treatment may have a cartilage protective effect. The slightly larger decrease of serum COMP in the resting group may reflect a lower clearance of COMP from the joint cavity. Serum osteocalcin was temporarily reduced, indicating a reversible suppression of bone formation.
Lay Rescuer Automated External Defibrillator (“Public Access Defibrillation”) Programs
Authors: Mary F. Hazinski, Ahamed H. Idris, Richard E. Kerber, Andrew Epstein, Dianne Atkins, Wanchun Tang, Keith Lurie
Journal: Circulation (2005)

Lay rescuer automated external defibrillator (AED) programs may increase the number of people experiencing sudden cardiac arrest who receive bystander cardiopulmonary resuscitation (CPR), can reduce time to defibrillation, and may improve survival from sudden cardiac arrest. These programs require an organized and practiced response, with rescuers trained and equipped to recognize emergencies, activate the emergency medical services system, provide CPR, and provide defibrillation. To determine the effect of public access defibrillation (PAD) programs on survival and other outcomes after SCA, the National Heart, Lung, and Blood Institute, the American Heart Association (AHA), and others funded a large prospective randomized trial. The results of this study were recently published in The New England Journal of Medicine and support current AHA recommendations for lay rescuer AED programs and emphasis on planning, training, and practice of CPR and use of AEDs. The purpose of this statement is to highlight important findings of the Public Access Defibrillation Trial and summarize implications of these findings for healthcare providers, healthcare policy advocates, and the AHA training network.
EG-11 * DYSREGULATION OF MGMT IN GLIOBLASTOMA: FRIEND OR FOE?
Authors: R. W. Rapkins, M. P. Hitchins, K. L. McDonald
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) is the most common and lethal form of brain cancer (median survival <15 months). The DNA alkylating agent, temozolomide, is used as the standard chemotherapeutic agent, resulting in mispairing of guanine with thymidine that leads to cellular arrest. However, in GBM patients the O6-methylguanine-DNA methyltransferase (MGMT) protein protects DNA from damage induced by temozolomide. Nevertheless, loss of MGMT expression is a frequent event in human malignancies and typically the result of MGMT promoter methylation. MGMT methylation has been strongly associated with the T-allele of the rs16906252 SNP (C/T) in colorectal carcinoma, pleural mesothelioma, and lung cancers. We therefore examined the T-allele and MGMT methylation in temozolmide-treated GBM patients. In 255 temozolomide-treated GBM patients, we found that the T-allele was significantly more frequent in patients with a methylated MGMT promoter. The unadjusted hazard ratio for death in carriers of the T-allele compared to wild-type, irrespective of methylation status, was 0.39 (95%CI:0.21-0.73; p = 0.003), indicating a 61% relative reduction in the risk for death of T-allele carriers. Surprisingly, GBM patients harboring the T-allele in the absence of MGMT methylation showed a survival benefit comparable to those with MGMT methylation (median survival: 15.5 months) and significantly better than the median survival of wild-type, unmethylated patients (median survival: 10.3 months). This suggests that the T-allele may reduce MGMT activity by mechanisms independent of methylation. Genotyping of 451 healthy controls indicated the frequency of carriage of the T-allele was 13% (MAF 0.065). In contrast, carriage of the T-allele in 160 GBM patients was 17%. Significantly, elevated risks were associated with carriage of the T-allele and development of GBM (odds ratio of 2.62 [95%CI:1.7-4.2]). We report that the T-allele (rs16906252) has predictive (response to temozolomide) and prognostic value (MGMT methylation and longer survival), but conversely may be a predisposing factor for the development of GBM.
Interferon beta produces only small benefits in multiple sclerosis
Authors: L. McKee
Journal: BMJ (1998)

Treatment of relapsing remitting multiple sclerosis with interferon beta produces only a small improvement in overall quality of life at considerable cost to the health service, according to a report commissioned by the NHS Executive's health technology assessment programme.

Researchers used existing data from clinical trials of interferon beta, information on the clinical course of multiple sclerosis, and new data on costs and quality of life to construct a model for calculating cost effectiveness. The cost effectiveness over five years was estimated …
Rectal examination and acid phosphatase.
Authors: A S Daar
Journal: BMJ (1981)

quick and dirty" look at the annual incidence of this condition in our own region.All HAA discharges from January 1975 to Scptember 1980 with a diagnosis of cirrhosis were included in the analysis.The earliest date of admission since 1975 was used to give the year in which new cases were identified, and the incidence rate was calculated from this.Since the HAA file is complete only up to September 1980 the probable incidence for 1980 has been calculated on the assumption of an even distribution of new cases through the year.Patients admitted to hospitals in this region but resident outside it were excluded; all patients resident in the region at the time of first hospital admission for cirrhosis were included, even if they later moved elsewhere.Validation of HAA diagnosis-for example, by liver biopsy-was not undertaken.Patients resident in the North Western Region but treated elsewhere were not included in this analysis.However, as such patients make up less than 2 00 of all hospital discharges, and as cirrhosis is responsible for only a very small proportion of all discharges, this is unlikely to affect the figures substantially.The average annual incidence of alcoholic cirrhosis in the North Western Region from 1976 to 1980 was 8 9/100 000.It rose from 6 4/100 000 in 1976 to 10 5/100 000 in 1980.The male: female ratio decreased from 3 1 in 1976 to 2 3 in 1980.This is because increasing numbers of women were diagnosed rather than decreasing numbers of men.These results are very similar to those described by Dr Saunders and others.Although our main interest lies in cirrhosis from other causes, particularly primary biliary cirrhosis, we thought that readers might find these figures an interesting confirmation of the large difference between England and Scotland in the incidence of hospital-diagnosed cirrhosis.
A novel transgenic mouse model for immunological evaluation of carcinoembryonic antigen–based DNA minigene vaccines
Authors: He Zhou, Yunping Luo, Masato Mizutani, Noriko Mizutani, Jürgen C. Becker, F. James Primus, Rong Xiang, Ralph A. Reisfeld
Journal: Journal of Clinical Investigation (2004)

A lack of relevant animal models has hampered preclinical screening and critical evaluation of the efficacy of human vaccines in vivo. Carcinoembryonic antigen–A2Kb (CEA–A2Kb) double transgenic mice provide a biologically relevant model for preclinical screening and critical evaluation of human CEA vaccine efficacy in vivo, particularly because such animals are peripherally tolerant of CEA. We established the utility of this model by demonstrating that an oral DNA minigene vaccine induces effective HLA-A2–restricted, CEA-specific antitumor CTL responses. This finding is supported by three lines of evidence: (a) an effective HLA-A2–restricted, CEA691-specific CTL response; (b) specific in vitro killing of CEA-A2Kb transduced MC-38 colon carcinoma cells; and (c) protective immunity induced in vaccinated mice against challenges of these tumor cells. Importantly, peripheral T cell tolerance against CEA in CEA-A2Kb double transgenic mice was broken by the CEA691 (IMIGVLVGV) minigene vaccine. In conclusion, CEA-A2Kb double transgenic mice were demonstrated to be good candidates for in vivo testing of human CEA–based vaccines. This result suggests a potential for these vaccines in future human vaccine development. The feasibility of using nonmutated self-antigens as targets for therapeutic vaccinations was indicated, provided that such antigens are presented in an immunogenic context; that is, as a DNA minigene in a bacterial carrier system.
Homocysteine Lowering and Severe Kidney Disease
Authors: Coen van Guldener
Journal: JAMA (2008)

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
Wiskott-Aldrich Syndrome Protein-Deficient Mice Reveal a Role for WASP in T but Not B Cell Activation
Authors: Scott B. Snapper, Fred S. Rosen, Emiko Mizoguchi, Paul Cohen, Wasif Khan, Ching-Hui Liu, Tracy L. Hagemann, Sau-Ping Kwan, Roger Ferrini, Laurie Davidson, Atul K. Bhan, Frederick W. Alt
Journal: Immunity (1998)
Diet and Infrequent Peritoneal Dialysis in Chronic Anuric Uremia
Authors: Sidney Levin, Jerry A. Winkelstein, Genevieve Barnes
Journal: New England Journal of Medicine (1967)

ALTHOUGH significant advances have been made in the fields of renal transplantation and chronic hemodialysis, these forms of therapy can be applied only to a select few of the several thousand patients afflicted each year with chronic uremia. Peritoneal dialysis offers the advantages of relative technical simplicity and wider application, but its use on a chronic basis has been limited because of relative inefficiency and the dangers of infection and adhesions.1 , 2 It is well known that some amelioration of uremia can be accomplished by diet alone.3 4 5 6 The dietary regimen described below, when combined with infrequent peritoneal dialysis, sustained the life . . .
The Molecular Basis of Severe Hemophilia B in a Girl
Authors: Perry Nisen, Judith Stamberg, Ralph Ehrenpreis, Susana Velasco, Ashok Shende, Jane Engelberg, Gungor Karayalcin, Lewis Waber
Journal: New England Journal of Medicine (1986)

Severe phenotypic expression of recessive X-linked disorders in females is rare, although examples have been reported. Cases have been documented in females who were homozygous for a recessive allele1 and in female patients with Turner's syndrome2 or a structural abnormality of the X chromosome.3 4 5 In females with apparently normal X chromosomes, "extreme lyonization" (that is, deviation from random X-chromosome inactivation) has been postulated to be the cause of severe clinical expression of X-linked recessive disorders.6 , 7 Nonrandom inactivation has been documented in females with structural X-chromosome abnormalities such as deletions8 , 9; inactivation of the abnormal X chromosome tends to minimize the . . .