tbuckley/cabot-search huggingface dataset:
Successful bone marrow transplantation in children with severe aplastic anemia using HLA‐partially matched family donors
Authors: Franco Locatelli, Fulvio Porta, Marco Zecca, Paolo Pedrazzoli, Rita Maccario, Simona Giani, Vito Vitale, Myriam Martinetti, Evelina Mazzolari, Arnalda Lanfranchi, Luigi Nespoli, Andrea Bacigalupo, Francesca Severi
Journal: American Journal of Hematology (1993)

Abstract Bone marrow transplantation (BMT) using HLA‐partially matched family donors has produced disappointing results (25–30% of long‐term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA‐partially matched family donor. Both cases presented 2 first class HLA‐antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine‐arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine‐A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long‐lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA‐identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA‐identical donor. © 1993 Wiley‐Liss, Inc.
Unilateral headache and loss of vision
Authors: G. Ohringer, T. Burke, A. Shaikh
Journal: BMJ (2014)

A 45 year old man was referred to the medical team with a one week history of unilateral headache associated with nausea and photophobia. Simple analgesia proved ineffective. His symptoms were relieved only by draping a towel over his eyes and head while avoiding movement. He usually had three or four self described “migraines” a year but said “this was the worst ever” and that he felt generally unwell.

On examination, he had marked epiphora in his right eye. Visual acuity was reduced to hand movements and the pupil was fixed and mid-dilated. Severe corneal oedema made funduscopy impossible. His left eye was white with visual acuity of 6/6. There was no fever or signs of meningism. Routine blood tests were unremarkable and a computed tomogram of the head was within normal limits.

The patient, who is of Middle Eastern descent, was normally fit and well and did not use regular drugs. He had no ocular history and denied trauma to the eye. He did not wear glasses.



### 1 What is the most likely diagnosis?

#### Short answer

Acute primary angle closure glaucoma (APACG).

#### Long answer

The presenting symptoms of nausea, headache, and photophobia are non-specific but can be indicative of serious neurological disease that requires urgent investigation and intervention. Subarachnoid haemorrhage and meningitis both deserve consideration, as well as some of the headache syndromes such as migraine and cluster headache. Although common to many neurological conditions, the patient’s symptoms could also have an ophthalmic cause so history taking and an appropriate examination are essential. Indeed, on closer questioning it may transpire that what was initially described as a headache is actually retro-orbital or ocular pain. Failure to consider ophthalmic disease properly and to clearly …
Prospective Study of Type 1 and Type 2 Diabetes and Risk of Stroke Subtypes
Authors: Mohsen Janghorbani, Frank B. Hu, Walter C. Willett, Tricia Y. Li, Joann E. Manson, Giancarlo Logroscino, Kathryn M. Rexrode
Journal: Diabetes Care (2007)

The aim of this study was to examine the relationship between type 1 and type 2 diabetes and risk of stroke subtypes in women.We followed 116,316 women aged 30-55 years in 1976 through 2002 for incidence of stroke. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for stroke.During 2.87 million person-years of follow-up, 3,463 incident strokes occurred. In multivariate analyses, the incidence of total stroke was fourfold higher in women with type 1 diabetes (relative risk [RR] 4.7 [95% CI 3.3-6.6]) and twofold higher among women with type 2 diabetes (1.8 [1.7-2.0]) than for nondiabetic women. The multivariate RR of ischemic stroke was increased sixfold (6.3 [4.0-9.8]) in type 1 diabetes and twofold (2.3 [2.0-2.6]) in type 2 diabetes. Risks for large-artery infarction and lacunar stroke were similar. Type 1 diabetes was also significantly associated with the risk of hemorrhagic stroke (3.8 [1.2-11.8]), but type 2 diabetes was not (1.0 [0.7-1.4]).Both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke.
Legal Issues Concerning Electronic Health Information
Authors: James G. Hodge, Jr, Lawrence O. Gostin, Peter D. Jacobson
Journal: JAMA (1999)

Personally identifiable health information about individuals and general medical information is increasingly available in electronic form in health databases and through online networks. The proliferation of electronic data within the modern health information infrastructure presents significant benefits for medical providers and patients, including enhanced patient autonomy, improved clinical treatment, advances in health research and public health surveillance, and modern security techniques. However, it also presents new legal challenges in 3 interconnected areas: privacy of identifiable health information, reliability and quality of health data, and tortbased liability. Protecting health information privacy (by giving individuals control over health data without severely restricting warranted communal uses) directly improves the quality and reliability of health data (by encouraging individual uses of health services and communal uses of data), which diminishes tort-based liabilities (by reducing instances of medical malpractice or privacy invasions through improvements in the delivery of health care services resulting in part from better quality and reliability of clinical and research data). Following an analysis of the interconnectivity of these 3 areas and discussing existing and proposed health information privacy laws, recommendations for legal reform concerning health information privacy are presented. These include (1) recognizing identifiable health information as highly sensitive, (2) providing privacy safeguards based on fair information practices, (3) empowering patients with information and rights to consent to disclosure (4) limiting disclosures of health data absent consent, (5) incorporating industry-wide security protections, (6) establishing a national data protection authority, and (7) providing a national minimal level of privacy protections.
Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer
Authors: Zheng Cai, Xiaolu Lei, Zhufen Lin, Jie Zhao, Feizhen Wu, Zhaoxiang Yang, Junxue Pu, Zhongqiu Liu
Journal: Acta Pharmaceutica Sinica B (2014)

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug "Tianma" (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.
175 TERLIPRESSIN GIVEN AS CONTINUOUS INTRAVENOUS INFUSION VERSUS TERLIPRESSIN GIVEN AS INTRAVENOUS BOLUSES IN THE TREATMENT OF TYPE 1 HEPATORENAL SYNDROME (HRS) IN PATIENTS WITH CIRRHOSIS
Authors: P. Angeli, S. Fasolato, M. Cavallin, E. Trotta, G. Maresio, A. Callegaro, A. Galioto, E. Mazza, A. Sticca, G. Benetti, A. Gatta
Journal: Journal of Hepatology (2009)
SEQUELAE OF ENCEPHALITIS LETHARGICA: NOTES ON 128 CASES
Authors: C. M. Smith
Journal: BMJ (1927)

CAN we demonstrato experimiientally the reason for the very localized starting-point of a tumour, althou'gh a great number of epithelial cells had been in contact during days and weeks with the cancer-producing agent (tar in the case of the experimental tar cancer)?
Aldosterone related blood volume expansion in cirrhosis before and during the early phase of ascites formation.
Authors: M Bernardi, F Trevisani, C Santini, R De Palma, G Gasbarrini
Journal: Gut (1983)

Thirty-seven patients with liver cirrhosis (16 without ascites: group 1; 21 with untreated ascites at the first onset: group 2) were studied during controlled sodium intake (40 mmol/day). Renal plasma flow, glomerular filtration rate, urinary sodium excretion, plasma sodium and potassium, plasma renin activity, plasma aldosterone concentration, blood volume, and arterial pressure were evaluated. All the patients had normal renal perfusion, plasma sodium and potassium, and arterial pressure. Mean plasma renin activity and plasma aldosterone concentration were significantly depressed in group 1 (p less than 0.001, p less than 0.005 respectively) compared with 21 normal controls in identical experimental conditions. This was possibly a consequence of expanded blood volume (p less than 0.001 compared with controls) which was directly correlated with plasma aldosterone concentration (p less than 0.001). In group 2 plasma renin activity and plasma aldosterone concentration were normal in over 50% of cases. Blood volume was lower than in group 1 (p less than 0.002), but again related to plasma aldosterone concentration (p less than 0.01). In both groups plasma aldosterone concentration was hyperbolically and inversely correlated with urinary sodium excretion, but the two curves were progressively shifted to the left in respect to controls suggesting an enhanced renal tubular sensitivity to the hormone. The results suggest that aldosterone related renal sodium retention, with consequent blood volume expansion, occurs before ascites formation. The mineralocorticoid activity of aldosterone is amplified by an enhanced sensitivity of renal tubules which appears to increase as the disease progresses.
One billion people are affected by global shortage of healthcare workers
Authors: P. Moszynski
Journal: BMJ (2011)

The critical shortage of skilled health personnel, especially in remote areas of the world, is a major obstacle to meeting the United Nations’ millennium development goals by 2015, say the organisers of the second Global Forum on Human Resources for Health, held last week in Bangkok.

The Global Health Workforce Alliance, a partnership of national governments, civil society groups, international agencies, finance institutions, researchers, educators, and professional associations that aims to bridge the gap in the supply of healthcare personnel, says that a billion people in 57 countries “face …
Activated Clotting Time as an Appropriate Test to Compare Heparin and Direct Thrombin Inhibitors Such as Hirudin or Ro 46-6240 in Experimental Arterial Thrombosis
Authors: Jean Pierre Carteaux, Alain Gast, Thomas B. Tschopp, Sébastien Roux
Journal: Circulation (1995)

Background Specific thrombin inhibitors are considered to be more potent antithrombotics than heparin. However, the relation between the systemic anticoagulation generated by thrombin inhibitors and their antithrombotic effect is not well defined. In a guinea pig carotid thrombosis model, the activated clotting time (ACT), the activated partial thromboplastin time (aPTT), and thrombin-generation tests were evaluated for their ability to predict the arterial antithrombotic effect of direct thrombin inhibitors such as hirudin and Ro 46-6240 compared with heparin. Methods and Results Thrombosis of the carotid artery was induced by subendothelial damage in guinea pigs, and the subsequent cyclic flow variations were monitored. The effects of pretreatment with intravenous heparin, hirudin, and Ro 46-6240 were tested. After doubling the baseline aPTT, 1 IU · kg −1 · min −1 heparin was inactive, whereas either hirudin or Ro 46-6240 (30 μg · kg −1 · min −1 ) prevented thrombus formation by 80%. Heparin (10 IU · kg −1 · min −1 ) induced the same antithrombotic effect but with indefinite aPTT prolongation. However, for similar prolongation of the ACT, the three compounds had equivalent antithrombotic effects. Thrombin generation was predictive of the antithrombotic effect of the thrombin inhibitors but not of heparin. Conclusions The arterial antithrombotic effect of direct thrombin inhibitors, when compared with those of heparin, should be evaluated by the ACT and not the aPTT or thrombin-generation assays. For a “therapeutic” aPTT prolongation, thrombin inhibitors induce higher systemic anticoagulation than does heparin and thus might unduly have higher bleeding liability.
In vivo differentiation of blast-phase chronic granulocytic leukemia. Expression of c-myc and c-abl protooncogenes.
Authors: C A Koller, V W Campbell, D A Polansky, A Mulhern, D M Miller
Journal: Journal of Clinical Investigation (1985)

A patient with chronic granulocytic leukemia in acute blastic transformation was treated with mithramycin, an RNA synthesis inhibitor, after in vitro exposure of her leukemic cells to mithramycin showed differentiation to normal appearing granulocytes. Mithramycin therapy in vivo resulted in a prompt and dramatic hematologic response. Before therapy, the patient's leukemic cells had high levels of transcription of the cellular myc and abl protooncogenes. After initiation of therapy, protooncogene mRNA decreased rapidly. These observations indicate that mithramycin can induce differentiation both in vitro and in vivo and suggest that such changes may be associated with altered oncogene expression.
Coronary Heart Disease and Job Stress in Two Cohorts of Bank Clerks
Authors: F. Kittel, M. Kornitzer, M. Dramaix
Journal: Psychotherapy and Psychosomatics (1980)

Two cohorts of Belgian bank clerks were observed during 10 years, with follow-up examinations at 5 and 10 years. Cohort I consisted of 447 males, aged 40-59, free of coronary heart disease at entry. They belong to a private bank whereas the 768 males of cohort II work in semipublic savings bank. 5 and 10 years' incidence of new "hard' coronary events (sudden deaths, myocardial infarction fatal or nonfatal) were significantly higher for cohort I as compared to cohort II. These differences are not explained through the major coronary risk factors introduced in a multiple logistic function, as expected hard events in cohort I were 50% higher than predicted by the MLF computed for cohort II.
Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.
Authors: C Walker, W Bauer, R K Braun, G Menz, P Braun, F Schwarz, T T Hansel, B Villiger
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
Increased renal vasodilator prostanoids prevent hypertension in mice lacking the angiotensin subtype-2 receptor
Authors: Helmy M. Siragy, Takaaki Senbonmatsu, Toshihiro Ichiki, Tadashi Inagami, Robert M. Carey
Journal: Journal of Clinical Investigation (1999)

The angiotensin subtype-1 (AT1) receptor mediates renal prostaglandin E2 (PGE2) production, and pharmacological blockade of the angiotensin subtype-2 (AT2) receptor potentiates the action of angiotensin II (Ang II) to increase PGE2 levels. We investigated the role of the AT2 receptor in prostaglandin metabolism in mice with targeted deletion of the AT2 receptor gene. Mice lacking the AT2 receptor (AT2-null) had normal blood pressure that was slightly elevated compared with that of wild-type (WT) control mice. AT2-null mice had higher renal interstitial fluid (RIF) 6-keto-PGF1α (a stable hydrolysis product of prostacyclin [PGI2]) and PGE2 levels than did WT mice, and had similar increases in PGE2 and 6-keto-PGF1α in response to dietary sodium restriction and Ang II infusion. In contrast, AT2-null mice had lower PGF2α levels compared with WT mice during basal conditions and in response to dietary sodium restriction or infusion of Ang II. RIF cAMP was markedly higher in AT2-null mice than in WT mice, both during basal conditions and during sodium restriction or Ang II infusion. AT1 receptor blockade with losartan decreased PGE2, PGI2, and cAMP to levels observed in WT mice. To determine whether increased vasodilator prostanoids prevented hypertension in AT2-null mice, we treated AT2-null and WT mice with indomethacin for 14 days. PGI2, PGE2, and cAMP were markedly decreased in both WT and AT2-null mice. Blood pressure increased to hypertensive levels in AT2-null mice but was unchanged in WT. These results demonstrate that in the absence of the AT2 receptor, increased vasodilator prostanoids protect against the development of hypertension.
Microvascular changes in the heart during chronic arterial hypertension.
Authors: G A Laine
Journal: Circulation Research (1988)

Changes of myocardial microvascular permeability in chronic renovascular arterial hypertension were studied. Hypertension was induced in dogs utilizing a one-kidney, one-clip Goldblatt model. Systemic arterial pressure, coronary sinus pressure, systemic venous pressure, myocardial lymph flow rate, myocardial interstitial fluid pressure, and the lymph-to-plasma protein concentration ratio for total plasma proteins and for beta-lipoprotein (CL/CP) were determined in control animals and 4-6 weeks following the Goldblatt procedure in hypertensive animals. Control values for the normotensive animals were 123 +/- 17 mm Hg, 7.3 +/- 1.3 mm Hg, 2.5 +/- 2.1 mm Hg, 3.1 +/- 2.1 ml/hr, 14.9 +/- 3.1 mm Hg, 0.82, and 0.33, respectively, while control values for the chronically hypertensive dogs were 160 +/- 20 mm Hg, 7.8 +/- 1.9 mm Hg, 2.9 +/- 2.5 mm Hg, 10.5 +/- 2.5 ml/hr, 24.8 +/- 3.7 mm Hg, 0.87, and 0.31, respectively. Under control conditions, myocardial lymph flow rate was significantly higher in the hypertensive group while no difference could be demonstrated in CL/CP between the two groups. This is indicative of either a change in myocardial microvascular permeability or an increase in microvascular exchange surface area. Coronary sinus pressure was elevated in both groups in order to increase transmicrovascular fluid flux and determine the filtration-independent reflection coefficient (sigma) for each group. Sigma is a surface area-independent indicator of microvascular permeability when determined for specific protein molecules at high transmicrovascular fluid fluxes.(ABSTRACT TRUNCATED AT 250 WORDS)