tbuckley/cabot-search huggingface dataset:
Subtypes of depression identified by the KDS-3A: a pilot study
Authors: P N Wold, K Dwight
Journal: American Journal of Psychiatry (1979)

To devise a system of classifying depression subtypes at intake, the authors administered the Kupfer Detre Scale (KDS-3A) to depressed outpatients at intake and after one, three, and six months of treatment with tricyclic antidepressants or lithium carbonate. None of the 10 tricyclic responders scored below 8 on the 14-point chronic anxiety scale at intake while 7 of the 12 lithium responders did, suggesting that any patient scoring below 8 is a probable candidate for lithium therapy. Patients scoring 8 or above on the chronic anxiety scale fell into two categories, those who had a low impulisivity score and responded to tricyclic antidepressants and those who had a high impulsivity score, responded to lithium, and had cyclothymic disorder or emotionally unstable character disorder.
Comprehensive sex therapy training: a new approach
Authors: V V Sadock, B J Sadock, H I Kaplan
Journal: American Journal of Psychiatry (1975)

The authors have developed a two-year part-time sex therapy training program for physicians. The first year emphasizes instruction in human sexuality as it relations to dysfunctional states. A highly selected group continues to a year of clinical experience using dual-sex (trainee-supervisor) therapy teams; trainess treat an average of four dysfunctional couples. The authors suggest that the program can serve as a possible model for other centers.
Correlation of PD-L1 expression with immune cell infiltrates, genome-wide copy number aberrations and survival in mesothelioma.
Authors: Bibhusal Thapa, Marzena Walkiewicz, Carmel Murone, Malaka Ameratunga, Khashayar Asadi, Siddhartha Deb, Xihui Lin, Adriana Salcedo, Stephen Barnett, Simon Knight, Paul Mitchell, Paul C Boutros, Neil Watkins, Thomas John
Journal: Journal of Clinical Oncology (2016)

8518 Background: Recent clinical studies using immune checkpoint inhibitors in mesothelioma (MM) have shown promise in shifting treatment paradigms. However, the immune environment and targets of these treatments such as program death receptor 1 (PD-1) and its ligand PD-L1 have not been well characterised in MM. In a large cohort of patients, we investigated PD-L1 expression, the surrounding immune infiltrate and genome-wide copy number status and correlated these parameters to clinicopathological features. Methods: Tissue microarrays (TMA) were constructed and stained with PD-L1 (E1L3N, CST, Massachusetts), CD4, CD8 and Foxp3 antibodies. PD-L1 positivity (PD-L1+) was defined as > 5% membranous staining regardless of intensity and high positive as > 50%. Genomic DNA obtained from tumour of a representative subset (68 patients) was used for genome-wide copy number analysis (CNA) using Affymetrix’s OncoScan platform. Percent Genome Aberrated (PGA) was computed for each sample. Results: Amongst 329 patients evaluated, the median age was 67 years. Most were male 274(83.2%). Epithelioid histology (N = 203; 62.9%) was the commonest. PD-L1+ was seen in 41.7% with high positivity in 9.6%. PD-L1+ correlated with non–epitheloid histology (P = < 0.0001) and increased infiltration with CD4, CD8 and FOXP3 lymphocytes. High PD-L1 expression correlated with worse prognosis (HR = 2.37; 95%CI: 1.57-3.56; P = < 0.0001) on univariate analysis. On multivariate analysis histology, stage, Neutrophil-Lymphocyte ratio (NLR) and ECOG status were found to be independently associated with survival, but not PD-L1+. PD-L1 gene (CD274) copy number gains were seen in seven (11.2%) of patients but did not correlate with PD-L1 expression. Higher PGA was seen in epithelioid histology, was not associated with PD-L1 expression but trended towards poorer survival (HR = 1.5; 95%CI: 0.89-2.68; P = 0.14). Conclusions: High PD-L1 expression was associated with non-epithelioid MM, poor clinical outcome and increased immunological infiltrates. Interestingly, increased genomic alterations did not correlate with PD-L1 expression but was associated with poorer survival.
Human LAT mutation results in immune deficiency and autoimmunity but also raises questions about signaling pathways
Authors: Arthur Weiss
Journal: The Journal of Experimental Medicine (2016)

The Journal of Experimental Medicine TCR signaling, necessary for normal T cell development and T cell function, proceeds through the induction of protein phosphorylation of downstream molecules, including the membrane-anchored adaptor LAT.LAT, a substrate of the ZAP70 tyrosine kinase, is phosphorylated on multiple tyrosines that serve as docking sites for the recruitment of several effector molecules, including PLCγ1, Gads/SLP-76, and Grb2/SOS, that are responsible for induced increase in Ca 2+ and activation of the Ras/MAPK pathway.Human immune deficiencies often reveal unexpected functions or highlight differences between human and mouse immune systems.In this issue, Keller et al. describe a family with three children that are homozygous for LAT mutations leading to premature LAT truncation, eliminating all of its known tyrosine phosphorylation sites.The clinical phenotypes of these patients were heterogeneous, characterized by aspects of immune deficiency and autoimmunity.Most noteworthy, some T cells developed in these patients.Interestingly, stimulation of the TCR on the T cells of the one patient that could be studied resulted in a substantial calcium increase and evidence of NF-κB activation but no Erk activation.The development of some T cells in these patients is surprising, as are the signaling studies.Germline deletion of LAT in mice results in profound early thymocyte developmental arrest, resulting in complete absence of peripheral T cells.It is possible that some LAT-related molecule might compensate for the loss of LAT function in the human, but efforts to identify such molecules were not productive.Alternatively, the truncated LAT protein might not represent a complete loss-offunction mutant.However, the authors examined the function of the truncated mutant in a LAT-deficient Jurkat T cell where they confirmed that the mutant LAT molecule did not support PLCγ1 phosphorylation, Ca 2+ increase, Erk phosphorylation, or CD69 induction.Thus, the authors' findings with the mutant LAT provided the expected phenotype based on previous studies with LAT mutants in Jurkat and in mice.So what accounts for the preserved signaling and somewhat preserved T cell development in the patient cells?There is no clear explanation.The mouse and Jurkat systems may differ from signaling systems in human T cells.Most puzzling, however, is the observation that increases in Ca 2+ and Erk, which are usually coupled and downstream of PLCγ1 activity, are discordant here.These studies would suggest a pathway leading to calcium increase that is dissociated from the activation of PLCγ1 operates in human but not in mouse or Jurkat T cells.These studies present an interesting and puzzling set of observations that await explanation.
Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects
Authors: Karina Stein, Stephanie Brand, André Jenckel, Anna Sigmund, Zhijian James Chen, Carsten J. Kirschning, Marion Kauth, Holger Heine
Journal: Journal of Allergy and Clinical Immunology (2016)
Provenance
Authors: J. O. Ballard
Journal: JAMA (2009)

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 Journals 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
Author's reply
Authors: Alan R Watson
Journal: BMJ (2007)

The guideline on urinary tract infection (UTI) in children from the National Institute for Health and Clinical Excellence (NICE) will precipitate debate, but hopefully cause less consternation than that expressed by Coulthard (previous letter). The published clinical guideline runs to 150 pages and 271 references with many systematic reviews.1 We can all quote observational studies that don't pass the scrutiny of evidence based medicine, but perhaps we should remember that the 1991 Royal College of Physicians guidelines were produced by 18 “experts” at a one day consensus meeting with medical audit in mind. Achieving a further consensus has been difficult, with imaging modalities changing from intravenous urogram and micturating cystogram for all to ultrasound, radionuclide imaging, and more selective cystograms. At the same time, recognition has been increasing that a lot of what we called reflux nephropathy is reflux associated damage in association with congenital dysplastic and obstructive kidneys.

The UTI algorithms that were devised didn't really distinguish between upper tract and lower tract infection. As most children only have a single episode and recover there has been legitimate concern about over-investigation. The NICE guideline does help us focus on important groups—young people and patients with unexplained fever, atypical UTI, or recurrent UTI. Prompt diagnosis and treatment are emphasised, but debate will continue about the relative merits of microscopy and dipsticks. One point to bear in mind is that UTI is a combination of symptoms and growth of organisms from an appropriately taken urine sample. Clinical decision making can be difficult, but it is clearly stated in the NICE guidelines that “the guidance does not, however, override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.” This may certainly be appropriate in the debated area of antibiotic prophylaxis. A recently published Cochrane review quoted only two small studies where no significant differences in risk for UTI were found between antibiotic prophylaxis and no treatment.2 We urgently need a controlled trial in this area, especially as compliance with long term prophylaxis is probably worse than we think and some parents and carers express concern about long term usage. However, children are our priority and we must justify to them the taking of the nasty medicine and the need for potentially nasty invasive tests.
Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria
Authors: Jeremy R. Beitler, Scott A. Sands, Stephen H. Loring, Robert L. Owens, Atul Malhotra, Roger G. Spragg, Michael A. Matthay, B. Taylor Thompson, Daniel Talmor
Journal: Intensive Care Medicine (2016)
The Antiproteolytic Reaction, Iodoacetate Index and Least Coagulable Protein Reactions in Relation to Malignant Neoplasia: Correlation of Tests<xref ref-type="fn" rid="fn1"><sup>1</sup></xref>
Authors: Eugene E. Cliffton, M.D.
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article The Antiproteolytic Reaction, Iodoacetate Index and Least Coagulable Protein Reactions in Relation to Malignant Neoplasia: Correlation of Tests Get access Eugene E. Cliffton, M.D. Eugene E. Cliffton, M.D. Department of Surgery (Oncology), Yale University School of Medicine, New Haven, Conn. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 3, December 1949, Pages 719–723, https://doi.org/10.1093/jnci/10.3.719 Published: 01 December 1949 Article history Received: 13 October 1949 Published: 01 December 1949
Case 12-1962
Authors: Alexander S. Nadas
Journal: New England Journal of Medicine (1962)

Presentation of CaseA six-week-old female infant was admitted to the hospital because of respiratory distress.The child was well until three days previously, when she began to feed poorly. One day before entry respiration became labored. Penicillin and tetracycline caused some improvement, but two hours before admission the respiratory difficulty increased, and an ashen color developed. She had coughed a few times, but no rhinorrhea or fever occurred.The child was the product of a normal sixth pregnancy of a healthy mother and at birth weighed 4 pounds, 11 ounces. The neonatal period was unremarkable except for a persistent . . .
18F-FDG PET/CT of Primary Cervical Granulocytic Sarcoma
Authors: Li-Chun Zheng, Xiang-Liu OuYang, Wen-Jun Zhang, Gui-Chao Liu, Xiao-Ming Zhang
Journal: Clinical Nuclear Medicine (2015)

Granulocytic sarcoma is an uncommon solid extramedullary tumor composed of immature leukocytes and commonly associated with acute myelogenous leukemia. Isolated granulocytic sarcoma in the cervix of uterus is exceedingly rare. Hereby we describe a case of FDG PET/CT finding of cervical granulocytic sarcoma without acute myelogenous leukemia in a 51-year-old patient.
Circulation clonale de Salmonella enterica sérovar Heidelberg en Italie
Authors: C Mammina, M Talini, M Pontello, A M Di Noto, A Nastasi
Journal: Eurosurveillance (2003)

L'etude decrite porte sur les caracteristiques phenotypiques et genetiques de 21 souches de Salmonella serovar Heidelberg isolees entre 1999 et 2003, provenant de differentes sources en Italie. Ont ete pris comme marqueurs epidemiologiques les profils de resistance aux antibiotiques, l'analyse plasmidique et le profil d'electrophorese en champ pulse. Malgre l'heterogeneite des deux premiers, les resultats de l'electrophorese en champ pulse sont en faveur d'une dissemination clonale a l'echelle nationale de ce serotype associe a la volaille.
Reduced Expression of HDAC3 Contributes to the Resistance Against HDAC Inhibitor, Vorinostat (SAHA) in Mature Lymphoid Malignancies
Authors: Jianming (Diane) Ding, Masaki Ri, Tomoko Narita, Ayako Masaki, Fumiko Mori, Asahi Ito, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Yukimasa Shiotsu, Akio Niimi, Shinsuke Iida
Journal: Blood (2012)
Sex Ratio in Offspring of Patients with Non-Hodgkin Lymphoma
Authors: H Olsson, L Brandt
Journal: New England Journal of Medicine (1982)

To the Editor: In a letter in the November 5 issue, Alperovitch and Feingold reported an increased sex ratio (male:female) among children of women with multiple sclerosis.1 We have observed a remarkably decreased sex ratio in the offspring of young adults with non-Hodgkin lymphoma. We recorded the sex of the children of 197 patients with this disease who were participating in an epidemiologic study and obtained the same information from a control group of 240 patients without any evident malignant disease. Interviewing the control patients established that they had mainly cardiovascular or respiratory disorders. The results of this study are. © 1982, Massachusetts Medical Society. All rights reserved.
Pharmacokinetics (PK) of crizotinib (PF-02341066) in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.
Authors: C. Li, C. Alvey, A. Bello, K. D. Wilner, W. Tan
Journal: Journal of Clinical Oncology (2011)

e13065 Background: Crizotinib is a selective, ATP-competitive, small molecule inhibitor of the ALK and MET/HGF receptor tyrosine kinases. Crizotinib is currently being developed as an orally administered agent in treatment of advanced ALK-positive NSCLC. The recommended clinical dose is 250 mg BID. Methods: Plasma crizotinib concentration data were collected in an ongoing, open-label, multi-center phase I study (J Clin Oncol 28:15s, 2010). A total of 167 patients receiving crizotinib at a dose of 250 mg BID who had at least 1 measurable plasma concentration of crizotinib were included in this PK analysis. Of these, 118 patients were ALK-positive NSCLC patients; and 42 were Asian and 125 were non‐Asian (including White, Black, and Other). The mean age was 51.0 years, and the mean weight was 70.7 kg. Results: After a single crizotinib dose of 250 mg, crizotinib Cmax was achieved at a median Tmax of 4.0 hours and the mean apparent terminal half life was 42 hours. Neither age, gender, race or body weight appeared to have overt effects on the single-dose crizotinib PK. After repeated dosing at 250 mg BID, crizotinib plasma concentrations appeared to reach steady state within 15 days. Crizotinib appeared to exhibit non-linear PK as reflected by decreases in CL/F observed with multiple dosing. The geometric mean values for CL/F following 15 and 28 Days of dosing of 64.5 L/hr and 60.1 L/hr, respectively, were lower than that seen after a single dose (100 L/hr). Crizotinib PK in the ALK-positive NSCLC patients was similar to that seen for patients with other tumor types. Mean values for crizotinib Cmax and AUC in Asian patients were 1.57- (90% CI: 1.16-2.13) and 1.50- (90% CI: 1.10 2.04) fold those seen in non-Asian patients, respectively. Comparison of BW-adjusted crizotinib PK parameters suggests that body size may be a factor that influences the observed PK difference. Conclusions: The observed change in CL/F prior to and after achievement of steady-state was likely due to autoinhibition of CYP3A. Increased systemic exposure to crizotinib was seen in Asian patients, however, based on the safety and efficacy profile, no dose adjustment is warranted seen in this population.
An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels
Authors: D H Mielke, D M Gallant, C Kessler
Journal: American Journal of Psychiatry (1977)

Sulpiride is a new and chemically different neuroleptic. In a study of 16 severely ill schizophrenic patients, this compound displayed definite evidence of antipsychotic activity while producing few adverse reactions. The relative absence of extrapyramidal side effects may indicate that sulpride has a low potential for producing tardive dyskinesia. Two patients who did not develop significant increases in prolactin levels did show a definite therapeutic response to sulpiride. Thus it appears that central dopaminergic blockade in the hypothalamic area is not a prerequisite for antipsychotic activity.
Case 45-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Allan I. Sandler, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. An 84-year-old man was admitted to the hospital because of pain in the hip.Five weeks previously he had fallen, with the immediate onset of pain in the left hip. There was a vague past history of episodic abdominal pain. He drank wine in quantities believed to be moderate.The temperature was 38.1°C, the pulse 100, and the respirations 20. The blood pressure was 110 systolic, 70 diastolic.Physical examination revealed a vigorous man. No lymph nodes were palpable. The lungs were clear. The heart was enlarged by 2 cm; the rhythm was irregular, and . . .
Updated results of a phase III randomized, controlled study of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL).
Authors: Jeffrey Alan Jones, Tadeusz Robak, Malgorzata Wach, Jennifer R. Brown, Alexander R. Menter, Elizabeth Vandenberghe, Loic Ysebaert, Nina D. Wagner-Johnston, Jonathan Polikoff, Farrukh Tauseef Awan, Xavier Camille Albert Badoux, Steven Coutre, Stephen Edward Forbes Spurgeon, Javier Loscertales, Lyndah Dreiling, Guan Xing, Sissy Peterman, Ronald L. Dubowy, Ian Flinn, Carolyn Owen
Journal: Journal of Clinical Oncology (2016)

7515 Background: Idelalisib (IDELA) is an oral PI3Kd inhibitor approved for use with rituximab in pts with relapsed CLL. This open-label study (NCT01659021) compared IDELA + ofatumumab (OFA) v OFA in pts with relapsed CLL. Results of the primary (1°) endpoint analysis were previously reported(Jones et al, ASCO 2015) and are updated here with an additional 8.5 mos of follow-up. In the 1° analysis, the combination yielded superior PFS and the KM estimated median OS was 20.9 and 19.4 mos in the IDELA+OFA and OFA arms. Methods: Pts with CLL progressing ≤ 24 mo from last therapy, who had received ≥ 2 cycles of a purine analogue or bendamustine, were randomized 2:1 to either Arm A (IDELA 150 mg BID continuously plus OFA, 300 mg IV wk 1, then 1 g IV q wk x 7 and q 4 wk x 4) or Arm B (OFA, same as Arm A except 2 g was substituted for 1 g dosing) with stratification factors relapsed v refractory, del17p and/or TP53 mutation, and IGHV mutation. The 1° endpoint was PFS based on IRC using modified IWCLL 2008 criteria. Results: Pt characteristics were balanced in the 2 arms: med age 67; Rai II/III/IV 18/13/51%, med no. prior regimens 3, refractory 49%, del17p/TP53mut 40%, IGHV unmut 78%. Exposure, disposition, and efficacy are shown in the table. Results were consistent across risk groups. Gr ≥ 3 AEs in Arm A included diarrhea/colitis (23.1%), pneumonia (19.7%), and pneumonitis (4.6%). Conclusions: With > 8 mos longer follow-up, IDELA + OFA vs OFA continues to show superior PFS and ORR, and now demonstrates superior OS in pts with del17p/TP53mut and a trend of improvement of OS in the ITT population. Clinical trial information: NCT01659021. Arm A (IDELA+OFA) N = 174 Arm B (OFA) N = 87 HR / OR2 Months on study (range) 16.1 (1.1 - 28.5)1 5.8 (0 - 25.4) - Reason for study D/C3 (%) 78 (44.8) 50 (57.5) - PD/Death 29 (16.7) 19 (21.8) - AE/Physician decision 15 (8.6) 17 (19.5) - Withdrew consent/other Med PFS4, mo 16.4 8.0 HR = 0.27, p < 0.0001 ORR, % 75.3 18.4 OR = 15.9, p < 0.0001 Q15 of OS4 (95% CI), mo 18.2 (12.3, 22.7) 12.7 (6.0, 19.3) - Med OS4 (95% CI), mo NR (25.8, NR) NR (21.7, NR) HR = 0.75, p = 0.27 Del17p/TP53mut: Med OS4 (95% CI), mo 25.8 (22.7, NR) 19.3 (10.7, NR) HR = 0.52, p = 0.03 1IDELA med exposure 12.3 mo (0.2-23.9); 2odds ratio;3per physician; 4KM estimation; 51st quartile
Medical boards often shield doctors guilty of sexual misconduct, investigation finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Sexual misconduct by doctors is common in the United States, but its extent is hard to determine because of a lack of transparency among state medical boards, a national investigation by the Atlanta Journal-Constitution has found.1 The newspaper launched the investigation after finding that in the state of Georgia two thirds of doctors disciplined for sexual misconduct were permitted to practice again.

The investigation found that US state medical boards often kept penalties secret, used vague language in public …