tbuckley/cabot-search huggingface dataset:
Effect of the PEG component of certolizumab pegol on calcium flux in cellular systems
Authors: G. Fossati, A. Nesbitt
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Certolizumab pegol (the only polyethylene glycolylated (PEG) Fab9 anti-tumour necrosis factor (CZP)) has a very low incidence of injection site pain (ISP) in clinical studies. This could be due to inhibition of mast cell degranulation by the CZP PEG component. Mast cells could be involved in mediating ISP: they are present at high numbers in the skin and can rapidly secrete inflammatory mediators in preformed granules. Changes in Ca<sup>2+</sup> flux are primary indicators of cell activation, and mast cell degranulation is preceded by Ca<sup>2+</sup> flux into the cell. PEG binds to metal ions (in particular Ca<sup>2+</sup>). The aim of this study was therefore to determine if PEG could inhibit Ca<sup>2+</sup> flux in a cellular system. <h3>Materials and methods</h3> Peripheral blood monocytes, isolated using MACS beads, were incubated with the fluorophore Fluo-4. Ca<sup>2+</sup> flux was measured using flow cytometry by detecting the Fluo-4 emission at 515–535 m. Ionomycin was added at 2 μg/ml and the emission measured over a 4 min period relative to background (assessed prior to ionomycin addition). The effect of a range of concentrations of the 40 kDa PEG component of CZP on Ca<sup>2+</sup> flux induced by ionomycin was assessed. The effect of PEG on an ionomycin-induced Ca<sup>2+</sup> flux in cultured mast cells was determined by a similar method but flux was measured using a fluorimeter. <h3>Results</h3> Ionomycin caused a dramatic flux of Ca<sup>2+</sup> in the monocytes. PEG caused a dose-dependent inhibition of Ca<sup>2+</sup> flux over a range of concentrations from a minimum of 40 mg/ml. This is a physiological concentration of PEG as the equivalent local concentration of PEG which is injected into patients is 88.9 mg/ml. The inhibitory concentration (IC<sub>50</sub>) for inhibition of the Ca<sup>2+</sup> flux caused by PEG was around 10 mg/ml. The maximum inhibition observed was 84.2% obtained at 40 mg/ml, with the effect titrating out around 1 mg/ml. In mast cells the IC<sub>50</sub> was around 11 mg/ml. <h3>Conclusion</h3> The PEG component of CZP inhibits Ca<sup>2+</sup> flux in monocytes and mast cells at a concentration relevant at the site of injection. This inhibition of Ca<sup>2+</sup> flux could potentially explain the low levels of ISP observed with CZP in the clinic. This effect would only be observed at the site of injection as systemic concentrations of the drug are below the levels where an effect is seen.
Autoimmune Hypoglycemia in a Type 2 Diabetic Patient With Anti-Insulin and Insulin Receptor Antibodies
Authors: Chong Hwa Kim, Tae Sun Park
Journal: Diabetes Care (2004)

The results of the 5th and final year, Fiscal Year 2003, are included in Table 1.We obviously did not come close to realizing this ambitious goal.In my 1998 Presidential Address, I compared the ADA to a large ship in which a new course first required a change of direction (which would occur slowly) before proceeding toward and hopefully reaching a new port.It's obvious that we have not reached that port, and realistically speaking, we probably never will.However, I would be remiss if I didn't point out the following.In each of the previous years, the increase in funding for Research Awards and Grants was much less than
Distribution of 2,4-D in air and on surfaces inside residences after lawn applications: comparing exposure estimates from various media for young children.
Authors: M G Nishioka, R G Lewis, M C Brinkman, H M Burkholder, C E Hines, J R Menkedick
Journal: Environmental Health Perspectives (2001)

We collected indoor air, surface wipes (floors, table tops, and window sills), and floor dust samples at multiple locations within 11 occupied and two unoccupied homes both before and after lawn application of the herbicide 2,4-D. We measured residues 1 week before and after application. We used collected samples to determine transport routes of 2,4-D from the lawn into the homes, its subsequent distribution between the indoor surfaces, and air concentration as a function of airborne particle size. We used residue measurements to estimate potential exposures within these homes. After lawn application, 2,4-D was detected in indoor air and on all surfaces throughout all homes. Track-in by an active dog and by the homeowner applicator were the most significant factors for intrusion. Resuspension of floor dust was the major source of 2,4-D in indoor air, with highest levels of 2,4-D found in the particle size range of 2.5-10 microm. Resuspended floor dust was also a major source of 2,4-D on tables and window sills. Estimated postapplication indoor exposure levels for young children from nondietary ingestion may be 1-10 microg/day from contact with floors, and 0.2-30 microg/day from contact with table tops. These are estimated to be about 10 times higher than the preapplication exposures. By comparison, dietary ingestion of 2,4-D is approximately 1.3 microg/day.
STUDIES ON ENTRY AND EGRESS OF POLIOMYELITIC INFECTION
Authors: Harold K. Faber, Luther Dong
Journal: The Journal of Experimental Medicine (1954)

At 56, 60, and 72 hours after simple feeding of poliomyelitis virus, typical, discrete lesions were found in the ganglia supplying the mouth and pharynx, which were most numerous and severe in the Gasserian ganglia. Lesions were also found in the nerve bundles adjacent to the infected ganglia. The character, localizations, and time of appearance of lesions point to nerve-conducted entry of infection from the mucosa of the mouth and pharynx. The possibility is suggested that under natural conditions of exposure, in which only small amounts of virus are involved, artificially induced immunity, active and probably passive, may block primary neural entry at the oropharyngeal portal by virtue of antibodies in the overlying mucus.
Side‐effects of complementary and alternative medicine
Authors: B. Niggemann, C. Grüber
Journal: Allergy (2003)

Complementary and alternative medicine are increasingly used to diagnose or treat allergic diseases, and numerous studies have reported benefits of this type of medicine. This article presents a review of the literature on risks of these methods. The potential sensitizing capacity of numerous herbal remedies may lead to allergic contact dermatitis and more rarely to IgE‐mediated clinical symptoms. Mechanical injuries may be observed following acupuncture leading to pneumothorax, cardiac tamponade or spinal injury. Infectious complications after acupuncture include hepatitis and bacterial endocariditis. Organ toxicity has been observed associated with various herbal preparations involving the liver, kidneys, and the heart. Some herbs may have cancerogenic properties. Severe nutritional deficiencies can occur in infants and small children given strict alternative diets, resembling ‘kwashiorkor’. Finally, among other miscellaneous adverse effects, adulteration with steroids, and herbal and drug interactions are discussed. The pattern of side‐effects is similar to that observed by the use of conventional medicine. Therefore, caution may be justified using both conventional and unconventional methods. Only if the benefit is proven and the side‐effects are established, should a given method be chosen.
Adult outcome of normal children who are short or underweight at age 7 years
Authors: L. Greco, C. Power, C. Peckham
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objectives</b>: To evaluate the adult growth outcome (at age 23) of children who are short or underweight at age 7 years in whom no identifiable pathological cause exists for their poor growth. <b>Design</b>: Longitudinal follow up of a birth cohort. <b>Setting</b>: The national child development study (1958 birth cohort) of Great Britain. <b>Subjects</b>: 523 children with a height or a weight below the fifth centile at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding ilness that could account for their poor growth. The remaining 453 subjects, who were followed to age 23, provided the base group from which those with additional data, such as parental height, were obtained. <b>Results</b>: 55/174 (31.6%) boys who were short at age 7 became short men; 60/211 (28.4%) girls who were short at age 7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%) were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7 became underweight women. Having short parents did not increase the probability of being small as an adult. Children with delayed puberty were as likely to remain small as those in whom puberty was not delayed. <b>Conclusions</b>: One in three normal children who was short or underweight at age 7 became a short or underweight adult. This informs the management of short children and may be valuable when prolonged growth hormone treatment for short stature is being considered. <h3>Key messages</h3> Key messages Follow up of national population samples starting early in life are ideal for monitoring such outcomes and associated mediating influences In this study one in three normal children who was short or underweight at age 7 became a short or underweight adult Fluctuating growth patterns in childhood are likely to account for the finding that the remaining two in three children were no longer short or underweight by early adulthood
STUDIES ON THE PNEUMONIC EXUDATE
Authors: Robert N. Nye
Journal: The Journal of Experimental Medicine (1922)

1. Washed cellular suspensions of pneumonic lungs, previously preserved with chloroform and toluene, contain a protease or proteolytic ferment, derived chiefly from the leucocytes of the exudate. 2. This protease is able to convert horse fibrin to a non-coagulable split product. In a pH range of 4.0 to 8.0 the digestion is slight at the most acid end. With decrease in acidity there is a gradual rise in activity to pH 6.0, and then a sharp increase up to the maximum digestion at pH 8.0. Judging from the amino nitrogen determinations, the most complete splitting occurs at pH 7.0. The degree of autolysis occurring in the pneumonic lung cellular suspension controls suggests that the active enzyme is identical with that causing the digestion of the fibrin. 3. Washed cellular suspensions of normal lungs, previously preserved with chloroform and toluene, contain a proteolytic enzyme which is active in a moderately acid medium (pH 4.0) and essentially inactive in less acid, neutral, and slightly alkaline media.
Local Surgical, Ablative, and Radiation Treatment of Metastases
Authors: R. D. Timmerman, C. S. Bizekis, H. I. Pass, Y. Fong, D. E. Dupuy, L. A. Dawson, D. Lu
Journal: CA A Cancer Journal for Clinicians (2009)

Because local therapies directed toward a specific tumor mass are known to be effective for treating early-stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination. However, with a higher likelihood of patients surviving longer after effective systemic therapy, even if not cured, the goal of the eradication of residual metastases via potent local therapies can be rationalized. However, this rationalization should be evidence-based so as to avoid harming patients for no established benefit. Although surgical metastectomy remains the most common and first-line standard among local therapies, nonsurgical alternatives, including thermal ablation and stereotactic body radiotherapy, have become increasingly popular because they are generally less invasive than surgery and have demonstrated considerable promise in eradicating macroscopic tumor. Rather than eliminating the need for local therapies, improvements in systemic therapies appear to be increasing the prudent utilization of modern local therapies in patients presenting with more advanced cancer.
Karaoke can damage singers voices and hearing
Authors: R. Dobson
Journal: BMJ (2003)

Researchers have confirmed what many people unlucky enough to listen to karaoke singing already knew—it can have adverse effects on health.

Strenuous singing can damage the voice and increase the risk of noise induced hearing loss, according to two new studies. The popularity of karaoke singing, where the singer's voice is amplified against background accompanying music, has spread from Asia to Europe and North America, but few studies had looked at its …
Immuno‐electronmicroscopic identification and localization of the antigenic proteins of tree pollen grains
Authors: M. Grote, H. Vik, S. Elsayed
Journal: Allergy (1988)

The localization of antigenic proteins on ultrathin sections of pollen grains represents an interesting approach to understanding the release mechanisms of these antigens when the pollen grains come in contact with various physiological fluids. Using different rabbit antibodies we have demonstrated the locations of these antigens in the various structures of pollen grains. We further demonstrated the cross‐reactivities between alder ( Alnus incana ), birch ( Betula verrucosa ) and hazel ( Corylus avellana ) pollen allergens. Ultrathin sections of the pollen grains were prepared and allowed to react with two individually raised rabbit antibodies, (Ab‐BV and Ab‐ALK), against birch pollen. The sites of the Ag/Ab complex on the sections were labelled by protein A/gold, and identified in a transmission electron microscope. The two birch antibodies showed either quantitative or qualitative differences regarding their binding to various structures on the pollen sections. Using Ab‐BV, the antigen‐binding sites were located in the apertural region of the pollen grain and in the cytoplasm, while almost no gold labelling could be seen on the pollen surface. With the other antibodies (Ab‐ALK), we could visualize the antigen‐binding locations on the surface material of the pollen grains, particularly in the exine part of the wall and in the cytoplasm. A few gold particles could also be seen in the apertural region of the pollen. In hazel and alder pollen the exine part of the wall was the most densely labelled, whereas the cytoplasm and the aperture bound smaller numbers of gold particles. Cross‐incubations: birch pollen incubated with antibodies against hazel (Ab‐GA), or alder (Ab‐AI), showed various intensities of gold labelling for each of the three species. Statistically, the differences in the number of gold particles bound per μm 2 grain section between birch, hazel and alder, were highly significant. The cross‐reactivities between these antigens from the three pollen species were further tested using house‐produced rabbit antisera against antigens of the three species by means of electrophoretic and autoradiographic techniques (GIE and GRIE). The three antibodies could precipitate the major IgE‐binding antigen from all three pollen species.
Limb Salvage and Amputation in Survivors of Pediatric Lower-Extremity Bone Tumors: What Are the Long-Term Implications?
Authors: Rajaram Nagarajan, Joseph P. Neglia, Denis R. Clohisy, Leslie L. Robison
Journal: Journal of Clinical Oncology (2002)

The past four decades have seen tremendous progress in the treatment of pediatric and adolescent cancers. As a consequence, there are increasing numbers of adult childhood cancer survivors. This has prompted investigation into the long-term consequences of cancer treatments. One group that merits special study is the survivors of lower-extremity bone tumors. Their function and quality of life may depend in part on both the surgery and the age at which it was performed. Comparisons between studies are difficult because small numbers of patients and the use of varying research designs and methods have limited research in this area. The purpose of this article is to review the major surgical approaches to lower-limb bone tumors and their impact on pediatric patients. The results show that survival is equivalent between amputation and limb salvage. Complications occur more frequently in limb salvage. The long-term outcomes of those undergoing amputation and limb salvage have not been found to be substantially different in regard to quality of life. In conclusion, prospective long-term follow-up of pediatric patients with lower-limb tumors is needed to (1) determine in a uniform manner the long-term complications, quality of life, and functionality of this population and describe differences within this patient population based on age at diagnosis and surgical procedure, (2) identify areas of concern that are amenable to intervention, and (3) provide clinicians and future patients a better understanding of the surgical options.
411 EFFECT OF INTRAPERITONEAL SALINE INFUSION FOR PERCUTANEOUS RADIOFREQUENCY ABLATION OF HEPATOCELLULAR CARCINOMA
Authors: W.Y. Tak, Y.J. Chung, S.Y. Lee, S.J. Yoon, S.Y. Park, E.S. Kim, M.K. Jung, S.W. Jeon, C.M. Cho, Y.O. Kweon, S.K. Kim, Y.H. Choi
Journal: Journal of Hepatology (2008)
A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase
Authors: Neal Weinreb, John Taylor, Timothy Cox, John Yee, Stephan vom Dahl
Journal: American Journal of Hematology (2008)

To assess the extent to which patients with type 1 Gaucher disease (GD1) receiving individualized enzyme replacement therapy with imiglucerase attain six defined therapeutic goals. One hundred and ninety-five GD1 patients enrolled in the ICGG Gaucher Registry, all of whom had data available for hemoglobin, platelet count, liver volume, spleen volume, bone pain, and bone crises at first infusion and after 4 years of therapy with imiglucerase, were evaluated for achievement of published therapeutic goals. The proportion of patients who met all six therapeutic goals increased from 2.1% at first infusion to 41.5% at 4 years; > or =5 goals from 12.8% to 76.9%; > or =4 goals from 37.4% to 92.8%; > or =3 goals from 70.8% to 99.0%; and > or =2 goals from 95.4% to 99.5%. All patients met at least one goal at first infusion and after 4 years of treatment. The proportion of patients meeting specific therapeutic goals increased for all parameters between first infusion and 4 years of therapy: platelet count (24.6%-79.5%), spleen volume (25.6%-78.5%), liver volume (45.6%-90.8%), bone pain (62.6-70.3%), hemoglobin (68.2-91.8%), and bone crises (91.8-99.0%). On average, patients who received higher doses of imiglucerase achieved a greater number of therapeutic goals. This analysis provides a benchmark for evaluating the utility of a disease management approach for GD1 based on monitoring achievement of therapeutic goals after treatment with imiglucerase.
Radio-Frequency Electrophrenic Respiration
Authors: John P. Judson
Journal: JAMA (1968)

Radio-frequency electrophrenic respiration (EPR) has been used successfully on a long-term intermittent basis to manage a patient with primary hypoventilation. The ability to use it only when desired, to adjust the amplitude of stimulation, and to control the rate of stimulation externally, has been made possible by use of the technique of radio-frequency transmission. Electrophrenic respiration by stimulation of one phrenic nerve has been carried out each night for ten months. Moderate fatigue of the stimulated diaghragm could be demonstrated after ten hours of stimulation. Further observation is required to determine if such fatigue is progressive. The future uses of radio-frequency electrophrenic respiration may include any condition of hypoventilation associated with an intact phrenic nerve and diaphragm. Whether its use will be of long-term benefit in the early stages of some hypoventilatory situations secondary to parenchymal disease is under study.
ERCP training: for the few, not for all
Authors: J BAILLIE
Journal: Gut (1999)

See article on page 154 

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that requires considerable training and experience to perform effectively and safely.1 It is the most dangerous procedure regularly performed by gastrointestinal endoscopists, with morbidity and mortality of 5–10% and 0.1–1%, respectively.2 In the United States, recommendations for ERCP training have evolved from ridiculously low “guesstimates” of procedure numbers required for competence3 (e.g. 25, 50) to the current consensus—based on a large prospective study4—that at least 180–200 diagnostic and therapeutic procedures are needed. ERCP is an integral part of the management of hepatobiliary and pancreatic (HBP) disorders, but it is only a part. Trainee gastroenterologists wishing to become experts in dealing with these disorders need to learn many clinical as well as procedural skills; it is useful to think of this as HBP training. The would be HBP specialist must work as part of a multidisciplinary team, and learn a great deal about body imaging (e.g. ultrasound, computed tomography, magnetic resonance), interventional radiology, gastrointestinal pathology and cytology, hepatology, oncology, surgery, and nutrition. Although perhaps only half of the cases seen in a specialist unit require ERCP, those intending to perform this procedure should be fully trained. There is no place for the purely “diagnostic” ERCP endoscopist: all endoscopists who perform ERCP must be able to decompress an obstructed biliary tree by sphincterotomy, stenting or nasobiliary drainage.5 The trained ERCP endoscopist’s success rate for cannulating the duct …
When is it time to get married? Or when should the assay user and the assay developer collaborate?
Authors: S H Swan, B L Lasley
Journal: Environmental Health Perspectives (1991)

Hormone assays are being developed in the laboratory to detect specific molecular markers in nonclinical populations. Epidemiology is increasingly using these assays to improve the precision with which disease processes and exposures can be defined. This growing body of molecular epidemiology requires a high degree of cooperation between the assay developer and the assay user. We draw on our experience in using a sensitive hormone assay for the detection of early pregnancy via urinary human chorionic gonadotropin to illustrate these points. We conclude that this collaborative effort, in addition to making this study possible, has provided unexpected rewards.
Magnetic Resonance Imaging of the Central Nervous System
Authors: Henry J. Kaminski
Journal: JAMA (1988)

To the Editor.—  The American Medical Association's Council on Scientific Affairs 1 sings the praises of magnetic resonance imaging (MR I) and indeed this praise is well deserved in many areas. Imaging of the posterior fossa and intrinsic spinal cord lesions is clearly superior with MR I. However, the enthusiasm for this new tool needs to be tempered in at least two very important areas.  In the evaluation of multiple sclerosis, MRI is much more sensitive in detecting abnormalities than computed tomography, but an abnormal study result is not synonymous with the disease. The diagnosis remains a clinical one. 2 In the study by Ormerod et al 3 of disseminated lesions in isolated optic neuritis, three of 37 controls had lesions on MRI consistent with multiple sclerosis. Kent and Larson 4 estimated a false-positive rate of 0.06 (false-positive studies divided by all positive studies in the studied population) from the