tbuckley/cabot-search huggingface dataset:
STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF MONKEYS
Authors: Peter K. Olitsky, Jerome T. Syverton, Joseph R. Tyler
Journal: The Journal of Experimental Medicine (1933)

In the bacteriological study here reported, we undertook an investigation of the flora associated with spontaneous conjunctival folliculosis. Following the plan of Noguchi (2), monkeys and chimpanzees were inoculated with the different organisms recovered from affected tissues. By this means, we disclosed among the bacteria a new species, Bacterium simiae, which was found to be specifically active, in that it induced follicular reactions in the conjunctiva apparently indistinguishable from the disease as it occurs in nature. The specific action of the bacterium in animals is the more striking when it is compared with the innocuousness of other organisms isolated from cases of folliculosis, and also when considered in relation to the behavior of quarantined animals. While the disease arises spontaneously in stock animals, of some 300 normal rhesus monkeys- these being isolated in lots of ten to twenty and quarantined from 6 to 14 weeks-not one has as yet shown folliculosis. With the insignificant exception already mentioned (1), the experimental disease was produced only when the inoculum contained either folliculosis tissue or cultures of the simian organism. Apart from these findings, the experimental results indicate that (a) the bacterium has thus far been recovered only from folliculosis cases and not from other forms of conjunctivitis nor from normal tissues; (b) the microorganism has been isolated not only from affected conjunctivae of stock monkeys but also from the tissue of animals- macaques and apes-experimentally infected with the bacterium, and (c) such recovered cultures have, in turn, been found to be specifically pathogenic in normal rhesus monkeys and chimpanzees. We may therefore postulate from this experimental study that an intimate relation exists between Bacterium simiae and spontaneous conjunctival folliculosis of simians.
The Hantaviruses, Etiologic Agents of Hemorrhagic Fever with Renal Syndrome: A Possible Cause of Hypertension and Chronic Renal Disease in the United States
Authors: J W LeDuc, J E Childs, G E Glass
Journal: Annual Review of Public Health (1992)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Dyspepsia, Helicobacter pylori, and peptic ulcer in a randomly selected population in India.
Authors: P H Katelaris, G H Tippett, P Norbu, D G Lowe, R Brennan, M J Farthing
Journal: Gut (1992)

There seems to be a worldwide geographic variation in the prevalence of peptic ulcer disease, although there are few reliable population based studies. This study aimed to determine the prevalence of peptic ulcer disease in a community in southern India and to evaluate the relationship between dyspeptic symptoms, Helicobacter pylori infection, gastritis, and peptic ulcer disease. A sample population was selected randomly from a rural monastic settlement in southern India. Subjects were interviewed using a standardised symptom and demography questionnaire then underwent upper endoscopy and antral biopsy for histology and CLO rapid urease test. Altogether 197 subjects from a population of 1499 (13.1%) were studied. All were male monks and ethnically Tibetan. The median age was 28 years (range: 21-81). None smoked or took NSAIDs. The six month period prevalence of dyspeptic symptoms was 68.5%. Current symptoms were present in 58.9% of subjects. Dyspepsia was more common in subjects aged 40 years or younger (p &lt; 0.0001). H pylori was detected in 77.2% subjects. There was no association between dyspepsia and the presence of H pylori or histological gastritis, although there was a strong correlation between symptoms and ulcer (p &lt; 0.003). The point prevalence of active peptic ulcer was 6.6% (13/197). All ulcers detected were either prepyloric or pyloroduodenal in location. A further 6.6% of subjects had definite evidence of scarring or deformity indicative of ulceration in the past. Subjects with past or present ulcers comprised 17.8% of dyspeptic subjects. H pylori was present in all subjects with active ulcers and in 12/13 of those with scarring. Dyspepsia, H pylori infection, gastritis, and peptic ulcer are all more common in this population than in those from developed countries. Ulcer disease, however, accounts for only a small proportion of subjects with symptoms and neither H pylori infection nor gastritis are significantly associated with the presence of dyspepsia.
Testicular Cancer: A Reflection on 50 Years of Discovery
Authors: Nasser Hanna, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

Introduction The advances in the treatment of testicular cancer are among the great achievements in medicine. Cancer researchers from around the globe have asked and answered nearly every fundamental question about the treatment of patients with testicular cancer. The results are astonishing: cure in 95% of all patients; refined surgical techniques that preserve sexual function; minimization of short-term and longterm toxicities of therapy; FDA approval of several agents due entirely or in part from trials in testicular cancer including vinblastine in the 1960’s, bleomycin in 1973, cisplatin in 1978, etoposide in 1983, and ifosfamide in 1988. This article will help the reader understand this journey to a cure, which in many ways mirrors the history of drug development and cancer management during the 20th century. The basic tenets of cancer care were established, reinforced, or challenged during the methodical study of testicular cancer. These tenets include the use of randomized clinical trials to minimize toxicity and maximize outcomes; the rational utilization of combination chemotherapy; and the integration of care involving medical and surgical specialties.
Historical perspectives in gonadotrophin therapy
Authors: Bruno Lunenfeld
Journal: Human Reproduction Update (2004)

The 20th century witnessed the steady development of knowledge about the reproductive process in animals and humans. These advances led to the identification of higher centres governing the dynamics of ovarian function and to the discovery of gonadotrophic hormones. As the mechanisms of action of these hormones became increasingly understood, they began to be used in the management of infertility during the early 1930s. Hormone extracts were originally prepared from animal pituitaries and pregnant mare serum, as well as from human pituitaries, placenta and urine, with pregnancies reported following their use in the late 1930s. This review traces the constant quest to reduce risks and improve safety and efficacy of hormone preparations for patients. It describes the complex path and perils leading to the pure hormone preparations that are available today, concluding with an optimistic glimpse towards the future. Small molecules that are orally active and specific are currently being investigated, some with the capacity to bypass many parts of the receptor conformation. Here lies the immediate future of this field, utilizing low-cost, small, defined molecules to stimulate follicle growth, ovulation and corpus luteum formation. Perhaps one day the classical gonadotrophins will no longer be required in clinical treatment.
A prescribing incentive scheme for non-fundholding general practices: an observational study
Authors: D N Bateman, M Campbell, L J Donaldson, S J Roberts, J M Smith
Journal: BMJ (1996)

To examine the effects of a financial incentive scheme on prescribing in non-fundholding general practices.Observational study.Non-fundholding general practices in former Northern region in 1993-4.Target savings were set for each group of practices; those that achieved them were paid a portion of the savings.Financial performance; prescribing patterns in major therapeutic groups and some specific therapeutic areas; rates of generic prescribing; and performance against a measure of prescribing quality.459 non-fundholding general practices, grouped into three bands according to the ratio of their indicative prescribing amount to the local average (band A > or = 10% above average, B between average and 10% above, C below average).102 (23%) of 442 practices achieved their target savings (18%, 19%, and 27% of bands A, B, and C respectively). Band C practices that achieved their target had a lower per capita prescribing frequency for gastrointestinal drugs, inhaled steroids, antidepressants, and hormone replacement therapy. There were no other significant differences in prescribing frequency, and no reduction in the quality of prescribing in achieving practices. Total savings of pounds 1.54 m on indicative prescribing amounts were achieved. Payments from the incentive scheme and discretionary quality awards resulted in pounds 463,000 being returned to practices for investment in primary care.The prescribing behaviour of non-fundholding general practitioners responded to financial incentives in a similar way to that of fundholding practitioners. The incentive scheme did not seem to reduce the quality of prescribing.
A Tumor Growth Inhibition Model for Low-Grade Glioma Treated with Chemotherapy or Radiotherapy
Authors: Benjamin Ribba, Gentian Kaloshi, Mathieu Peyre, Damien Ricard, Vincent Calvez, Michel Tod, Branka Čajavec-Bernard, Ahmed Idbaih, Dimitri Psimaras, Linda Dainese, Johan Pallud, Stéphanie Cartalat-Carel, Jean-Yves Delattre, Jérôme Honnorat, Emmanuel Grenier, François Ducray
Journal: Clinical Cancer Research (2012)

To develop a tumor growth inhibition model for adult diffuse low-grade gliomas (LGG) able to describe tumor size evolution in patients treated with chemotherapy or radiotherapy.Using longitudinal mean tumor diameter (MTD) data from 21 patients treated with first-line procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) chemotherapy, we formulated a model consisting of a system of differential equations, incorporating tumor-specific and treatment-related parameters that reflect the response of proliferative and quiescent tumor tissue to treatment. The model was then applied to the analysis of longitudinal tumor size data in 24 patients treated with first-line temozolomide (TMZ) chemotherapy and in 25 patients treated with first-line radiotherapy.The model successfully described the MTD dynamics of LGG before, during, and after PCV chemotherapy. Using the same model structure, we were also able to successfully describe the MTD dynamics in LGG patients treated with TMZ chemotherapy or radiotherapy. Tumor-specific parameters were found to be consistent across the three treatment modalities. The model is robust to sensitivity analysis, and preliminary results suggest that it can predict treatment response on the basis of pretreatment tumor size data.Using MTD data, we propose a tumor growth inhibition model able to describe LGG tumor size evolution in patients treated with chemotherapy or radiotherapy. In the future, this model might be used to predict treatment efficacy in LGG patients and could constitute a rational tool to conceive more effective chemotherapy schedules.
Cortical and Subcortical Contributions to Activity-Dependent Plasticity in Primate Somatosensory Cortex
Authors: Edward G. Jones
Journal: Annual Review of Neuroscience (2000)

After manipulations of the periphery that reduce or enhance input to the somatosensory cortex, affected parts of the body representation will contract or expand, often over many millimeters. Various mechanisms, including divergence of preexisting connections, expression of latent synapses, and sprouting of new synapses, have been proposed to explain such phenomena, which probably underlie altered sensory experiences associated with limb amputation and peripheral nerve injury in humans. Putative cortical mechanisms have received the greatest emphasis but there is increasing evidence for substantial reorganization in subcortical structures, including the brainstem and thalamus, that may be of sufficient extent to account for or play a large part in representational plasticity in somatosensory cortex. Recent studies show that divergence of ascending connections is considerable and sufficient to ensure that small alterations in map topography at brainstem and thalamic levels will be amplified in the projection to the cortex. In the long term, slow, deafferentation-dependent transneuronal atrophy at brainstem, thalamic, and even cortical levels are operational in promoting reorganizational changes, and the extent to which surviving connections can maintain a map is a key to understanding differences between central and peripheral deafferentation.
Phase II Evaluation of Low-Dose Oral Etoposide for the Treatment of Relapsed or Progressive AIDS-Related Kaposi’s Sarcoma: An AIDS Clinical Trials Group Clinical Study
Authors: Scott R. Evans, Susan E. Krown, Marcia A. Testa, Timothy P. Cooley, Jamie H. Von Roenn
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Liposomal anthracyclines and paclitaxel are considered the best available cytotoxic therapies for Kaposi’s sarcoma (KS), but relapse is common. To identify new interventions for relapsed or progressive KS, a phase II study of low-dose etoposide to assess its toxicity and efficacy was conducted. PATIENTS AND METHODS: Thirty-six patients with high-risk KS were treated with oral etoposide 50 mg/d for 7 consecutive days of every 2-week cycle. All patients’ disease had relapsed or progressed after prior combination chemotherapy or anthracycline therapy. For patients without a complete or partial response after two cycles of therapy and no toxicity greater than grade 2, the dose of etoposide was escalated to 100 mg/d orally on days 1 to 7 of each 14-day cycle. Treatment-related and disease-specific quality of life was evaluated using patient reports on the General Health Self-Assessment Form and a KS-specific measure. RESULTS: One patient achieved a complete response, 12 patients had a partial response (overall response rate, 36.1%), and stable disease was observed in 12 patients (33.3%). Tumor responses were seen in all disease sites. Fourteen patients had their dose escalated, of whom five responded. The median time to response was 17.7 weeks; the median duration of response was 25 weeks. The most frequent hematologic abnormality was neutropenia, which was grade 4 in seven patients and grade 3 in six. Opportunistic infections occurred in eight patients during the treatment period. Both response to treatment and toxicity influenced patient-reported quality of life. CONCLUSION: We conclude that low-dose oral etoposide at a dose of 50 mg/d is safe and effective for the treatment of refractory or progressed AIDS-related KS and has an overall positive effect on the quality of life of responding patients.
Intradialytic Parenteral Nutrition Does Not Improve Survival in Malnourished Hemodialysis Patients
Authors: Noe[Combining Diaeresis]l J.M. Cano, Denis Fouque, Hubert Roth, Michel Aparicio, Raymond Azar, Bernard Canaud, Philippe Chauveau, Christian Combe, Maurice Laville, Xavier M. Leverve
Journal: Journal of the American Society of Nephrology (2007)

Although intradialytic parenteral nutrition (IDPN) is a method used widely to combat protein-calorie malnutrition in hemodialysis patients, its effect on survival has not been thoroughly studied. We conducted a prospective, randomized trial in which 186 malnourished hemodialysis patients received oral nutritional supplements with or without 1 year of IDPN. IDPN did not improve 2-year mortality (primary end point), hospitalization rate, Karnofsky score, body mass index, or laboratory markers of nutritional status. Instead, both groups demonstrated improvement in body mass index and the nutritional parameters serum albumin and prealbumin (P < 0.05). Multivariate analysis showed that an increase in prealbumin of >30 mg/L within 3 months, a marker of nutritional improvement, independently predicted a 54% decrease in 2-year mortality, as well as reduced hospitalizations and improved general well-being as measured by the Karnofsky score. Therefore, although we found no definite advantage of adding IDPN to oral nutritional supplementation, this is the first prospective study demonstrating that an improvement in prealbumin during nutritional therapy is associated with a decrease in morbidity and mortality in malnourished hemodialysis patients.
ORGANELLES AND TRAFFICKING MACHINERY FOR POSTSYNAPTIC PLASTICITY
Authors: Matthew J. Kennedy, Michael D. Ehlers
Journal: Annual Review of Neuroscience (2006)

Neurons are among the largest and most complex cells in the body. Their immense size and intricate geometry pose many unique cell-biological problems. How is dendritic architecture established and maintained? How do neurons traffic newly synthesized integral membrane proteins over such long distances to synapses? Functionally, protein trafficking to and from the postsynaptic membrane has emerged as a key mechanism underlying various forms of synaptic plasticity. Which organelles are involved in postsynaptic trafficking, and how do they integrate and respond to activity at individual synapses? Here we review what is currently known about long-range trafficking of newly synthesized postsynaptic proteins as well as the local rules that govern postsynaptic trafficking at individual synapses.
Circulating T cell subtypes in polymyalgia rheumatica and giant cell arteritis: variation in the percentage of CD8+ cells with prednisolone treatment.
Authors: G S Panayi
Journal: Annals of the Rheumatic Diseases (1994)

Matters arising al7 did not show the results of their assay in patients with other rheumatic diseases.However, the fact that 2/5 of their control sera were also positive indicates that their assay is not specific.Finally, since ANA are found in a very large proportion of pauciarticular onset JCA patients (88% in our study), we do not think that the presence of anti-RA 33 antibodies in this particular subset of patients could add any useful in- formation.In addition, anti-RA 33 antibody assay is clearly longer to perform and less widely available than ANA test.In conclusion, we think that there is not enough evidence to support a wider use of APF and anti-RA 33 antibody assay in JCA.
Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals.
Authors: G L Stahl, B Halliwell, J C Longhurst
Journal: Circulation Research (1992)

Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 mumols) to the gallbladder (n = 14) significantly (p less than 0.05) increased mean arterial blood pressure (MAP) by 37 +/- 6 mm Hg, left ventricular dP/dt by 1,893 +/- 416 mm Hg/sec, heart rate by 6 +/- 1 beats per minute, and systemic vascular resistance from 0.34 +/- 0.01 to 0.42 +/- 0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 mumols H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p less than 0.05) attenuated 44 mumols H2O2-induced increases in MAP from 36 +/- 3 to 2 +/- 2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 mumols H2O2-induced increases in MAP from 40 +/- 7 to 19 +/- 10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2 activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion.
Surfactant protein B and RAGE increases in the plasma during cardiopulmonary bypass: a pilot study
Authors: P. Agostoni, C. Banfi, M. Brioschi, D. Magrì, S. Sciomer, G. Berna, C. Brambillasca, G. Marenzi, E. Sisillo
Journal: European Respiratory Journal (2010)

Surfactant derived protein B (SPB) and plasma receptor for advanced glycation end products (RAGE) have been proposed as markers of lung injury. The former is produced specifically by pneumocytes while RAGE production is present in several body tissues. Cardiopulmonary bypass (CPB) generates a transient lung injury. We measured SPB and RAGE in plasma before surgery and after CPB, as well as 24 h and 48 h later. We analysed plasma samples from 20 subjects scheduled for elective coronary artery bypass grafting. We performed a quantitative analysis of plasma levels of RAGE and SPB mature form (8 kDa) by ELISA and a semi-quantitative analysis of SPB immature form (∼40 kDa) by Western blotting. Surgery procedures were uneventful. After CPB RAGE median (75th–25th interquartile difference) increased from 633 (539) pg·mL −1 to 1,362 (557) pg·mL −1 (p&lt;0.01), while mature SPB increased from 5,587 (3,089) ng·mL −1 to 20,307 (19,873) ng·mL −1 (p&lt;0.01). RAGE and mature SPB returned to normal values within 48 h. This behaviour was confirmed when RAGE and SPB were normalised for protein content. Parallel changes were observed for immature SPB. Plasma RAGE and SPBs are sensitive and rapid markers of lung distress.
MHC Class II–Mediated Apoptosis by a Nonpolymorphic MHC Class II Peptide Proceeds by Activation of Protein Kinase C
Authors: Weiping Zang, Safa Kalache, Marvin Lin, Bernd Schroppel, Barbara Murphy
Journal: Journal of the American Society of Nephrology (2005)

It was demonstrated previously that a peptide derived from a conserved region of MHC class II, HLA-DQA1, inhibits proliferation of allogeneic T cells in vitro. Administration of HLA-DQA1 in conjunction with allogeneic cells at the time of priming or at the time of rechallenge prevented the development of the delayed type hypersensitivity response in vivo. The immunomodulatory effects of HLA-DQA1 were associated with the induction of apoptosis in B cells, macrophages, and dendritic cells via a caspase-independent pathway. This study investigated the binding site and mechanism that mediates cell death induced by HLA-DQA1. It was demonstrated that HLA-DQA1 binds to MHC class II on the cell surface, causing MHC class II signaling, initiation of protein kinase C signaling, and mitochondrial membrane depolarization with resultant apoptosis. The data indicate that HLA-DQA1 binds to MHC class II outside the groove, in a manner similar to superantigen. These results suggest that HLA-DQA1 is a novel immunotherapy that may provide an effective means of targeting professional antigen-presenting cells, in particular B cells.