tbuckley/cabot-search huggingface dataset:
Steroids and depression
Authors: A. Mitchell, V. O'Keane
Journal: BMJ (1998)

Adrenal steroids are commonly prescribed drugs, the central effects of which are rarely alluded to in routine clinical practice or systematically investigated in medical research. Glucocorticoids are important in the pathogenesis of depression, but this potentially serious psychological side effect is often overlooked in clinical practice.

The unwanted behavioural effects of anabolic steroids are widely known, but those of glucocorticoid therapy, though recognised for over 45 years, receive less attention. Placebo controlled studies have reported that a third of patients taking glucocorticoids experience significant mood disturbance and sleep disruption.1 More importantly, up to 20% of patients on high dose glucocorticoids report psychiatric disorders including depression, mania, psychosis, or a mixed affective state.2 A recent double blind placebo controlled trial of corticosteroid administration in healthy individuals showed that 75% of subjects developed disturbances in mood and cognition, which reversed when steroids were stopped.3 We do not know the characteristics of those who are vulnerable to adverse effects, but those with higher cumulative dosages …
P16.17 * F-18-FET PET IMAGING FOR DIAGNOSIS OF LATE PSEUDOPROGRESSION IN PATIENTS WITH HIGH-GRADE GLIOMAS
Authors: S. Kebir, N. Schafer, F. Mack, C. Schaub, M. Niessen, G. Stoffels, N. Galldiks, K. Langen, M. Glas, U. Herrlinger
Journal: Neuro-Oncology (2014)

BACKGROUND: Pseudoprogression is characterized by increasing contrast-enhancement in the tumor area mimicking tumor progression, which, however, remains stable or subsides in control MRI 4-8 weeks later. Pseudoprogression is thought to be a sign of response to therapy rather than rapid tumor growth. It mainly occurs within three months after radiochemotherapy but it is increasingly observed that pseudoprogression may also develop substantially later and may be particularly difficult to distinguish from true tumor progression which is much more prevalent at this stage. As conventional MRI lacks specificity for pseudoprogression, there is still an unmet need for additional imaging modalities in this setting. PATIENTS AND METHODS: Twenty-two clinically stable patients diagnosed with high-grade glioma were examined by F-18-fluoroethyl-tyrosine PET (FET PET) at the time of either new contrast enhancement or ≥25% increase of an existing contrast-enhanced lesion on conventional MRI ≥12 weeks after last radiochemotherapy. For static analysis, maximum and mean tumor/brain ratios (TBRmax, TBRmean) of FET uptake were determined. In addition, dynamic FET PET parameters were analysed: time-to peak (TTP) and time-activity curve patterns. Diagnosis of late pseudoprogression or progression was established according to RANO criteria relying on follow-up MRI obtained at least 6-8 weeks from the index MRI and served as reference for PET data evaluation. RESULTS: Based upon follow-up MRI 11 patients were diagnosed with late pseudoprogression, in 72.7% (8 out of 11) of whom MGMT methylation was tested positive. Both TBRmax and TBRmean were significantly lower compared with progressive tumor (TBRmax, 2.12 ± 0.22 vs. 3.63 ± 0.18; TBRmean, 1.47 ± 0.17 vs. 2.19 ± 0.05; both p < 0.001). Receiver-operating-characteristic (ROC) analysis yielded an optimal cut-off of 3.05 for TBRmax (sensitivity, 100%; specificity, 91.7%; AUC, 0.96; 95% CI, 0.88 - 1.0; p < 0.001) and 1.95 for TBRmean (specificity, 91.7%; sensitivity, 77.8%; AUC, 0.94; 95% CI, 0.47 - 1.0; p = 0.001). ROC analysis of TTP revealed at an optimal cutoff of 19 min a sensitivity of 100% along with a specificity of 90% for predicting pseudoprogression (AUC, 0.92; 95% CI, 0.76 - 1.0; p = 0.01). However, there was no significant association between the type of curve pattern and the diagnosis of late pseudoprogression (χ2 (1) = 3.19, p = 0.117). CONCLUSION: F-18-FET PET may provide valuable information for the assessment of late pseudoprogression. Systematic prospective analyses are warranted.
The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.
Authors: C Hassager, B J Riis, V Strøm, T T Guyene, C Christiansen
Journal: Circulation (1987)

The long-term effect of percutaneous and oral estrogen replacement therapy on blood pressure, plasma renin substrate, and serum estrogens was examined in a 2 year placebo-controlled study with 110 early postmenopausal women. The women were allocated to four treatment groups: (1) oral cyclical combination of 2 mg estradiol valerate and cyproterone acetate, (2) oral placebo, (3) percutaneous 17 beta-estradiol, supplemented by 200 mg oral progesterone during the second year, or (4) percutaneous placebo cream. Systolic and diastolic blood pressure remained unchanged in both hormone treatment groups, whereas the diastolic blood pressure tended to increase in both placebo groups. Plasma renin substrate increased during oral treatment with estradiol, but remained unchanged with percutaneous estradiol. No correlation was found between blood pressure and plasma renin substrate. During percutaneous administration of estradiol, the serum concentrations of estrone and estradiol continued to rise after 3 months and reached a plateau at 6 months of therapy. Serum estrone but not estradiol showed the same pattern during oral estradiol therapy. No further changes in any of the measured variables were observed in the women treated with percutaneous estradiol after addition of cyclical oral progesterone. We conclude that both oral and percutaneous treatment with estradiol may provide protection against the age-related increase in diastolic blood pressure observed in early postmenopausal women, and that the metabolic steady state is not attained until after 3 months of estradiol therapy.
Panautonomic Dysfunction and Guillain-Barré Syndrome
Authors: Richard L. Levy
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In response to the letter from Michael I. Weintraub, MD (242:513, 1979), autonomic dysfunction is a well-documented complication of Guillain-Barré syndrome. In his review of 28 patients, Lichtenfeld<sup>1</sup>found that the disease took the form of either excessive or insufficient sympathetic or parasympathetic activity, or both. Hypertension was seen in 61% of the patients, postural hypotension in 43%, abnormal sweating and flushing in 15% to 25%, and ECG abnormalities in 64%. Dr Weintraub makes a provocative suggestion, that early Swan-Ganz monitoring be used to predict incipient autonomic dysfunction in those patients with Guillain-Barré syndrome. However, as the following case illustrates, there are simpler, less invasive methods of making the diagnosis and, in fact, because of the rapid fluctuations in autonomic activity, the Swan-Ganz measurements are of limited therapeutic value in those patients. <h3>Report of a Case.—</h3> A 39-year-old man came to a Veterans Administration Hospital with
Cure of Exomphalos in a Two-hour-old Infant
Authors: B. S. S. Acharya, R. W. Burslem
Journal: BMJ (1948)

MEDICAL MEMORANDA.which yielded another pint (570 ml.) of yellow pus.On this latter finding the cavity was drained after the instillation of 100,000 units of penicillin.Convalescence following operation was uneventful.The pus from the abscess was sterile and yielded no amoebae.Repeated examinations of the stools failed to demonstrate the entamoeba, either in the cyst or vegetative form.X-ray examination of the bowel showed no pathological change.Sigmoidoscopy at this stage revealed the smooth, pale, glassy and rather rigid mucous membrane associated with chronic amoebiasis.A full anti-amoebic course was therefore given, the response being immediate and dramatic.This patient was carefully questioned in order to elicit a possible source of infection.He lives in a Surrey suburb.Neither he nor any of his family has ever been out of the country, nor have any of his friends or business associates.He had no illnesses or symptoms until the day of admission to hospital.
Interferon-γ/CCR5 expression in invariant natural killer T cells and CCL5 expression in capillary veins of dermal papillae correlate with development of psoriasis vulgaris
Authors: F. Kono, T. Honda, W. Aini, T. Manabe, H. Haga, T. Tsuruyama
Journal: British Journal of Dermatology (2013)

Background There have been extensive studies regarding which types of T lymphocytes are involved in psoriasis vulgaris (PV). However, it has remained unclear which types of T lymphocytes might directly contribute to psoriasiform epidermal and vascular hyperplasia. Objectives To understand the role of T-cell receptor (TCR)Vα24+ invariant natural killer (iNK)T cells in the development of PV. Methods Seventeen patients were enrolled in this study. Using biopsy samples of PV plaques, TCRVα24+ iNKT cells were investigated regarding their cytokine production to understand their roles in development of disease. Results The number of interferon (IFN)-γ+ iNKT cells correlated with the length of the psoriasiform hyperplasia rete ridge and the Psoriasis Area and Severity Index. IFN-γ+ iNKT cells in psoriatic skin exhibited higher C-C chemokine receptor (CCR)5 expression, and the amount of C-C chemokine ligand (CCL)5, a ligand for CCR5, was increased in capillary veins of psoriasis plaques. CCR5+ iNKT-cell numbers significantly correlated with the number of capillary vein endothelial cells expressing CCL5 in PV. Furthermore, the number of CCL5+ capillary veins correlated with the maximum rete ridge length. Conclusions IFN-γ/CCR5 expression in iNKT cells and CCL5 expression in vessels of dermal papillae correlate with the development of psoriasiform hyperplasia and microabscess. We propose that these iNKT cells may become useful targets for development of novel therapeutic approaches to PV.
Abnormal Extracellular Matrix Protein Transport Associated With Increased Apoptosis of Vascular Smooth Muscle Cells in Marfan Syndrome and Bicuspid Aortic Valve Thoracic Aortic Aneurysm
Authors: Maria Nataatmadja, Malcolm West, Jenny West, Kim Summers, Philip Walker, Michio Nagata, Teruo Watanabe
Journal: Circulation (2003)

Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)-2 in VSMC apoptosis was studied in MS aneurysm.Aneurysm tissue was obtained from patients undergoing surgery (MS: 4 M, 1 F, age 27-45 years; BAV: 3 M, 2 F, age 28-65 years). Normal aorta from subjects with nonaneurysm disease was also collected (4 M, 1 F, age 23-93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS (27+/-8%) and BAV (32+/-14%) compared with control (7+/-5%).In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.
Radiation Exposure and Cancer-Reply
Authors: V. P. Bond
Journal: JAMA (1981)

In Reply.—  Drs Lyon and Gardner beg the question, since they begin by accepting as valid the very point that our editorial challenged. We did not gloss over the issues, nor did we impugn the motives of the authors of these studies. Furthermore, if we have interpreted their remarks correctly, they place at least equal weight on studies of small populations as on those of large. However, there is one point they raise that requires specific comment.  The consistencies between the studies cited by Lyon and Gardner are questionable. In neither the findings on the Marshallese nor the Caldwell study on military personnel present at Smoky at 1957 were all of the doses of radiation necessarily low. In the Marshallese, a single case of leukemia developed in the group exposed to an estimated 175 rad of external radiation, hardly ascribable to a low dose of fallout. One does not know
CEA for Monitoring Colon Cancer-Reply
Authors: Charles G. Moertel
Journal: JAMA (1994)

In Reply.  —Dr Chu and associates criticize our study because we did not regiment and standardize the conduct and interpretation of CEA monitoring. It was not our intention to do so. We wished only to document the results of monitoring as employed by a large and diverse group of physicians reasonably representative of those in cancer practice today. In this setting the CEA test performed poorly. If after nearly 30 years of CEA use American physicians haven't learned to do it right, it is doubtful that they ever will. Furthermore, if there is some nuance in the use of the CEA test that could accomplish the sow's-ear-to-silk-purse phenomenon, the burden of proof must be borne by those who make this claim.  Drs Corman and Prager wishfully hope for some additional tests that will allow more rational decisions to be made regarding CEA-directed surgical intervention. They point to laparoscopy or immunoscintigraphy,
Leonard Anthony Price
Authors: B. Williams
Journal: BMJ (2002)

Oncologist whose chemotherapy research promised better survival rates with fewer side effects


Len Price trained in medical oncology at the Royal Marsden Hospital and was senior lecturer at the Institute of Cancer Research from 1973 to 1980. Working with Bridget Hill he showed that the antileukaemic drug DDMP—a diaminopyrimidine derivative of the antimalarial pyrimethamine—discarded on account of toxicity to bone marrow, was an effective and safe treatment for solid tumours when used in combination with folinic acid. They went on to show that the side effects of antitumour drugs, particularly the damage to bone marrow, were markedly reduced and that patients had a better quality of life if the drugs were administered intensively over 24 hours every three or four weeks rather than over several consecutive days. 




Moving to the London Clinic he developed this approach, especially for the adjuvant treatment of breast cancer in younger women with poor prognostic factors. Using the Price-Hill method he was able to give ultra-high doses of a combination of eight anticancer drugs over 24 hours, together with peripheral blood stem cell rescue. This research was proceeding when he died. It promises to achieve better survival rates with fewer side effects than combinations of fewer drugs at lower doses given with bone marrow transplantation.

He lectured on these themes all over the world. His work was followed with close interest at the Chemotherapy Foundation in New York, on whose scientific committee he was the UK representative.

In 1989 he had a myocardial infarction. Three years later he had a heart transplant. He worked to within a month of his death. He leaves a wife, Val; two children; and three grandchildren.

Consultant physician London Clinic (b London 1935; q London 1962; MD, MRCP), died from multiple organ failure on 19 December 2001.
Urinary Fibrinogen Derivative Excretion and Intraglomerular Fibrin Deposition in Glomerulonephritis
Authors: P. Naish, D. J. Evans, D. K. Peters
Journal: BMJ (1974)

The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur. Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.
A Structural and Dynamic Investigation of the Facilitating Effect of Glycoprotein IIb/IIIa Inhibitors in Dissolving Platelet-Rich Clots
Authors: J.Ph. Collet, G. Montalescot, C. Lesty, J.W. Weisel
Journal: Circulation Research (2002)

Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors were shown recently to facilitate the rate and the extent of pharmacological thrombolysis. However, their synergistic potential with rtPA in dissolving thrombotic vaso-occlusions is not fully understood. We have therefore developed a dynamic and structural approach for analysis of fibrinolysis to assess the inhibiting effect of platelets and the facilitating effect of GPIIb/IIIa inhibitors in dissolving platelet-rich clots (PRCs). Fluorescent rtPA was used to study the architecture of PRCs, to follow the progression of the rtPA binding front, and to measure the lysis-front velocity using confocal microscopy. Fibrinolysis resistance of PRCs was related to a reduction of both rtPA binding and lysis-front velocities of platelet-rich areas compared with platelet-poor areas (2.4 +/- 0.2 versus 3.5 +/- 0.4 microm/min for rtPA binding velocity, P=0.04, and 1.2 +/- 0.6 versus 2.8 +/- 0.2 microm/min for lysis-front velocity, P=0.008, in platelet-rich and platelet-poor areas, respectively). Fibrinolysis appeared heterogeneous, leaving platelet-rich areas un-lysed. Adding pharmacological concentrations of abciximab (0.068 micromol/L) or eptifibatide (1 micromol/L) before clotting decreased the average surface of platelet-rich areas by 64% (P=0.0005) and 72% (P=0.0007), respectively. The resulting equalization of rtPA binding rate and rtPA binding-front velocity between platelet-rich and platelet-poor areas led to a 3-fold increase of the lysis-front velocity in platelet-rich areas of either abciximab-PRC (P=0.006) or eptifibatide-PRC (P=0.03). The overall lysis rate of treated-PRC was increased by 74% compared with control-PRC (P<0.01). These results demonstrate that fibrinolysis resistance of PRCs is related primarily to the heterogeneity in the clot structure between platelet-rich and platelet-poor areas. GP IIb/IIIa inhibitors facilitate the rate and the extent of fibrinolysis by improving rtPA binding velocity and, subsequently, the lysis rate in platelet-rich areas. These findings provide new insights on the synergistic potential of GP IIb/IIIa inhibitors and fibrinolytic agents.
Proliferative retinopathy in a woman with growth hormone deficiency and diabetes mellitus.
Authors: C H Thivolet, P Mirakian, P Chatelain, P Fournier, J Tourniaire
Journal: BMJ (1990)

In each of two years 1-2% of all patients referred as emergencies had had a seizure. One fifth of the patients who had just experienced their first fit were treated with an anticonvulsant drug. Current practice recommends starting treatment only after two or more seizures have been witnessed by someone else.4 Almost one fifth of the patients with first seizures were discharged immediately, some without an outpatient appointment. Just over half spent less than 48 hours in a short stay facility; a third were subsequently lost to follow up. Three fourths of those attending as outpatients were seen in a general medical clinic. The immediate care of patients who have a first seizure is important because over half can be expected to have a further seizure within five years.Early referral to a specialist will avoid a premature diagnosis of epilepsy and unnecessary treatment with anti convulsant drugs. Regular review will prepare the patient for the diagnosis and ensure that suitable treatment is started. Patients who present to our casualty department with a first fit are now reviewed urgently at our epilepsy clinic.
Targeting the endocannabinoid system in the treatment of fragile X syndrome
Authors: Arnau Busquets-Garcia, Maria Gomis-González, Thomas Guegan, Carmen Agustín-Pavón, Antoni Pastor, Susana Mato, Alberto Pérez-Samartín, Carlos Matute, Rafael de la Torre, Mara Dierssen, Rafael Maldonado, Andrés Ozaita
Journal: Nature Medicine (2013)
Cellular and humoral immunity to hepatitis-B surface antigen in active chronic hepatitis.
Authors: W M Lee, W D Reed, C G Mitchell, R M Galbraith, A L Eddleston, A J Zuckerman, R Williams
Journal: BMJ (1975)

The hepatitis-B surface antigen (HBsAG) may be persistently present in the serum in a few cases of active chronic hepatitis but the cause of the disease in most patients is unknown. In a study of 39 HBsAg-negative cases cell-mediated immunity to HBsAg was observed in 24 (62%), suggesting a high frequency of previous infection with the hepatitis-B virus. Hepatitis-B surface antibody was detectable by radioimmunoassay in six patients, in all of whom complexes of HBsAg were present in the serum on electron microscopy. Out of 12 patients with HBsAg-positive active chronic hepatitis who were also studied eight, including all those untreated at the time, showed a cellular response to the antigen. Evidence of sensitization to a liver-specific cell surface lipoprotein was found with similar frequency in the two groups. These results are consistent with the hypothesis that hepatitis-B virus infection is important in initiating the disease in many cases of active chronic hepatitis and that sensitization to the liver cell membrane antigen is the autoimmune process responsible for the perpetuation of the liver injury.
Research Activities of Faculty in Academic Departments of Medicine
Authors: HARRY N. BEATY
Journal: Annals of Internal Medicine (1986)

To assess the involvement of current medical faculty in research, a research activities questionnaire and a faculty roster form were sent to all full-time, salaried faculty of departments of medicine in medical schools in the United States. Valid responses from 7483 faculty members were received from 119 medical schools. About 88% of respondents are men; 83% have M.D. degrees; 8% have a Ph.D. degree; and 7% have both degrees. Twenty-four percent of the faculty who have done research had little preparation for a research career. However, 45% of faculty with M.D. degrees had 2 or more years of research training. Seventy-seven percent of faculty with only an M.D. degree reported research activity from 1982 to 1983; the median effort of all faculty with an M.D. is 25%. Faculty with both degrees are more involved in research and the median effort for those with a Ph.D. is 95%.