anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time.

There are several analytical methods used to estimate megestrol acetate plasma concentrations, including gas chromatography-mass fragmentography (GC-MF), high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). The GC-MF and HPLC methods are specific for megestrol acetate and yield equivalent concentrations. The RIA method reacts to megestrol acetate metabolites and is, therefore, non-specific and indicates higher concentrations than the GC-MF and HPLC methods. Plasma concentrations are dependent, not only on the method used, but also on intestinal and hepatic inactivation of the drug, which may be affected by factors such as intestinal tract motility, intestinal bacteria, antibiotics administered, body weight, diet and liver function.

The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5 to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7 to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1 and 94.7% (mean 86.2%). Megestrol acetate metabolites which were identified in urine constituted 5 to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.

Plasma steady state pharmacokinetics of megestrol acetate were evaluated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of megestrol acetate oral suspension for 21 days. Plasma concentration data obtained on day 21 were evaluated for up to 48 hours past the last dose.

Mean (±1SD) peak plasma concentration (Cmax) of megestrol acetate was 753 (±539) ng/mL. Mean area under the concentration time-curve (AUC) was 10476 (±7788) ng x hr/mL. Median Tmax value was five hours. Seven of 10 patients gained weight in three weeks.

Additionally, 24 adult, asymptomatic HIV seropositive male subjects were dosed once daily with 750 mg of megestrol acetate oral suspension. The treatment was administered for 14 days. Mean Cmax and AUC values were 490 (±238) ng/mL and 6779 (±3048) ng x hr/mL, respectively. The median Tmax value was three hours. The mean Cmin value was 202 (±101) ng/mL. The mean % of fluctuation value was 107 (±40).

The effect of food on the bioavailability of megestrol acetate oral suspension has not been evaluated.
PURPOSE:To industrially and advantageously obtain the titled compound useful as an anesthetic agent, etc., by successively reacting an N-substituted Tyr ester with a Gly ester in the presence of a specific enzyme in an aqueous medium, then reacting the resultant reaction product with a Gly ester, Phe ester and then Leu amide. CONSTITUTION:An N-substituted tyrosine (Tyr) lower alkyl ester is reacted with glycine (Gly) lower alkyl ester in the presence of serine protease (e.g. alpha-chymotrypsin) in an aqueous medium containing a water-soluble organic solvent (e.g. dimethylformamide) and the resultant product is then reacted a glycine lower alkyl ester and phenylalanine (Phe) lower ester in the presence of thiol protease (e.g. papain). The obtained reaction product is subsequently reacted with leucinamide (Leu amide) in the presence of serine protease to extend the peptide and afford the aimed compound.
Only prescribers registered in the CD TOUCH® Prescribing Program may prescribe TYSABRI for Crohn's disease [see Warnings and Precautions (5.2)]. 

The recommended dose of TYSABRI for Crohn's disease is 300 mg intravenous infusion over one hour every four weeks. TYSABRI should not be used with concomitant immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or concomitant inhibitors of TNF-α. Aminosalicylates may be continued during treatment with TYSABRI. 

If the patient with Crohn's disease has not experienced therapeutic benefit by 12 weeks of induction therapy, discontinue TYSABRI. For patients with Crohn's disease who start TYSABRI while on chronic oral corticosteroids, commence steroid tapering as soon as a therapeutic benefit of TYSABRI has occurred; if the patient with Crohn's disease cannot be tapered off of oral corticosteroids within six months of starting TYSABRI, discontinue TYSABRI. Other than the initial six-month taper, prescribers should consider discontinuing TYSABRI for patients who require additional steroid use that exceeds three months in a calendar year to control their Crohn's disease.
Participants with advanced solid tumors will receive JNJ-87704916 alone and in combination with cetrelimab. Ascending dose levels will be sequentially tested.
Manual cranial therapy consisting of massage and cranial relaxing techniques, lasting 30 minutes each session approximately, for 3 weeks and one month follow-up. Manual therapy consists of a prone and supine cranial massage.
OBJECTIVE: Diabetes mellitus (DM) is an important risk factor for the development of osteoarthritis (OA), increasing OA progression and OA pain. To gain insight into the underlying mechanisms of how DM exacerbates OA processes and OA pain, this study analyzed histological differences of synovial tissues from non-DM and DM patients with OA and correlated these differences with knee pain severity.
MATERIALS AND METHODS: Synovial tissue was obtained from 12 non-DM and 10 DM patients with advanced knee OA who underwent total knee arthroplasty. Synovial inflammation was assessed using the Synovitis score developed by Krenn. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess knee pain intensity and disability in OA patients. The number of mast cells, macrophages, nerve fibers, capillaries, larger vessels and erythrocyte extravasation were analyzed microscopically in histological and immunostained synovial sections from non-DM and DM patients. Association analyses were performed to determine associations between OA knee pain and synovial changes affected by DM.
RESULTS: Synovial tissue from OA patients with DM had a higher synovitis score, more erythrocyte extravasation, and contained higher numbers of mast cells and macrophages compared to non-DM patients. The number of capillaries and vessels in the lining/sublining layer of the synovial tissue was reduced in DM patients. OA patients with DM had more severe knee pain compared to non-DM patients. The KOOS pain score was associated with the synovitis score, the number of tissue macrophages, and the number of mast cells in the synovial tissue (adjusted for age, sex, and BMI). In addition, the erythrocyte extravasation score was associated with the KOOS pain score and with the synovitis score.
CONCLUSION: The study suggests that increased OA progression and pain severity in patients with DM result from more pronounced synovitis and synovial vascular leakage and increased infiltration of macrophages and mast cells.
For the retrospective study, we will enrol 3,000 patients \>18 years old who underwent CCTA and meet all of the inclusion and exclusion criteria, with at least 4-year follow-up. The primary endpoint and patient characteristics will be those of the CTP-PRO study. Since women are less affected by CAD, at a ratio of 35:65, to correct for this expected imbalance we will weight recruitment to obtain relatively sex-balanced cohorts. In subgroups of patients, available data from invasive coronary angiography, FFR and OCT will be collected to help develop, test and refine the diagnostic performance of the automated AI tools.
Previously, we demonstrated that palmatine (PALM) - an isoquinoline alkaloid from Berberis sibrica radix, exerted antiseizure activity in the pentylenetetrazole (PTZ)-induced seizure assay in larval zebrafish. The aim of the present study was to more precisely characterize PALM as a potential anticonvulsant drug candidate. A range of zebrafish and mouse seizure/epilepsy models were applied in the investigation. Immunostaining analysis was conducted to assess the changes in mouse brains, while in silico molecular modelling was performed to determine potential targets for PALM. Accordingly, PALM had anticonvulsant effect in ethyl 2-ketopent-4-enoate (EKP)-induced seizure assay in zebrafish larvae as well as in the 6 Hz-induced psychomotor seizure threshold and timed infusion PTZ tests in mice. The protective effect in the EKP-induced seizure assay was confirmed in the local field potential recordings. PALM did not affect seizures in the gabra1a knockout line of zebrafish larvae. In the scn1Lab-/- zebrafish line, pretreatment with PALM potentiated seizure-like behaviour of larvae. Repetitive treatment with PALM, however, did not reduce development of PTZ-induced seizure activity nor prevent the loss of parvalbumin-interneurons in the hippocampus of the PTZ kindled mice. In silico molecular modelling revealed that the noted anticonvulsant effect of PALM in EKP-induced seizure assay might result from its interactions with glutamic acid decarboxylase and/or via AMPA receptor non-competitive antagonism. Our study has demonstrated the anticonvulsant activity of PALM in some experimental models of seizures, including a model of pharmacoresistant seizures induced by EKP. These results indicate that PALM might be a suitable new drug candidate but the precise mechanism of its anticonvulsant activity has to be determined.
The present invention relates to a method for manufacturing Chinese medicine viscosity reducing capsules and application thereof. The capsule is prepared in a mode that raw guangdong earthworm, raw leech, centipede, radix et rhizoma rhei, oriental wormwood and red sage root are processed by specified methods, ground and loaded into the capsules. The capsules are mainly suitable for treating and preventing hyperviscous blood diseases, can also prevent and treat cerebral infarction diseases, and have the functions of preventing and treating hypertensive diseases. The use method of the capsules comprises the following steps that: a relevant patient takes the medicine three times in one day and takes two capsules every time; one month is a treatment course. Then, the patient's blood flow variation index changes are inspected. If pathogenetic conditions are improved, a second treatment course can be carried out; if the pathogenetic conditions are slightly normal, the patient can take the capsules three times in one day, and takes one capsule every time to maintain therapeutic effects.
COPD is a leading cause of morbidity and mortality worldwide. Comorbid diseases are an important factor in the prognosis and functional capabilities of COPD patients. There is a relationship between cardiac comorbidity and COPD exacerbation frequency within COPD patients. The main objective of this study is to compare the rate of moderate-severe COPD exacerbations in patients of all COPD severities with and without cardiovascular diseases. Secondary objectives will characterize the prevalence, severity and incidence over time of comorbidities and explore the relationships between comorbidities and rate of COPD exacerbations, force expiratory volume in 1 second (FEV1) decline and quality of life. This will be a prospective, observational, non-drug interventional, non-randomized study that will be carried out in up to 8 European countries. All patients will be enrolled by GP outpatient clinics and data will be collected over 4 visits (screening \[-3 months\], baseline, 12 months post baseline 24 months post baseline) and, additionally by 6 telephone calls (at 3, 6, 9, 15, 18 and 21 months post baseline). The study population will consist of 3330 evaluable patients with diagnosed COPD of any severity grade with and without comorbidities. Subjective and objective data on pre-defined comorbidities will be collected and analyzed.
Acute leukemia is a heterogeneous group of clonal diseases. Leukemia relapse remains the main cause of treatment failure, including the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. The investigator's previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD positive AML patients, which was associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Recent studies have shown that sorafenib is also effective in patients with FLT3-negative acute leukemia. The investigator's previous exploratory study found that salvage therapy such as sorafenib combined with chemotherapy and donor lymphocyte infusion could significantly improve the CR rate and survival in patients with recurrent FLT3-negative acute leukemia after allo-HSC. More and more studies have shown that sorafenib and allo-HSCT have synergistic GVL effect. Some studies have demonstrated that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the exact mechanism of sorafenib enhancing the GVL effect and the influence of gut microbiome on sorafenib maintenance after allo-HSCT in FLT3 negative acute leukemia patients remain unknown.
Participants in this group will be prescribed to routine respiratory care, Routine respiratory care involves the use of a standard incentive spirometer that is not a digital device and does not include any built-in reminder. As per routine care, the nurse or respiratory therapist will remind the subjects to perform a series of at least 10 deep breaths every hour.
A method is claimed for prepg. proteins or peptides without a terminal methionine gp. from peptides and proteins with the sequence Met-Y-X-Pro-A (I), where X = Thr, Ala or Ser; Y = an amino acid sequence contg. at least two residues, which ends with the sequence Pro (or when X = Ser) can end with Pro-Ala-Pro; A = a further amino acid sequence. The method involves transforming a prokaryotic cell with a recombinant DNA and/or a recombinant vector coding for (I). The transformed cell is cultivated and the Met-Y-X-Pro-A is recovered from the medium, and cleaved with an IgA protease. The first cleavage prod., a G-CSF deriv. which has the sequence X-Pro-A, is isolated. Also claimed is the recombinant G-CSF itself and medicaments contg. it. USE/ADVANTAGE - The X-Pro-A produced has no N-terminal methionine; such peptides are difficult to synthesise by prior methods. It is a G-CSF deriv. useful for treatment of cancer and leukaemia, in bone marrow transplants, and for treating burns and opportunistic infections affecting patients with weakened immune systems.
Infants 6 weeks of age, part of the dose-finding cohort, randomized to receive 3 doses of the iNTS-GMMA Dose A vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with the following vaccines: Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine administered concomitantly during the last iNTS-GMMA administration at Day 232, and the pentavalent vaccine (DTPwHepB-Hib), the Pneumococcal conjugate vaccine, and the inactivated polio vaccine administered at the same time, at 6, 10 and 14 weeks of age, at the local EPI vaccination centers, and not part of the current clinical trial.
Total 37 patients who had undergone PCNL were included between June 2007-June 2009. All patients were evaluated routinely with physical examination, complete blood count (CBC), blood urine nitrogen (BUN), creatinine levels, and urinalysis. None of the patients had experienced pyelonephritis, and none had a solitary kidney, renal ectopy or history of any other urinary abnormality. At least one of the following techniques; namely computed tomography (CT), intravenous urography or ultrasonography, was preferred routinely before surgery in order to visualize the urinary system. Unilateral PCNL was performed in all patients. Postoperative CBC and BUN creatine levels were repeated.

Preoperative DMSA scans were performed a day before the surgery, whereas postoperative scans were randomized to indicate early and late term. The aim of randomization was to determine an optimal time for assessing patients. A DMSA scan was read by using a technique that divides both kidneys into three paired poles. In addition the uptake of all opposite poles was measured together and calculated as a percentage value separately (Figure-1), e.g., the two upper poles' uptake was measured together as if they were renal units and each poles' own portion in this total uptake was declared separately as a percentage. How the differential functions were changed between the sides undergoing PCNL and the opposite sides, as well the changes before and 6 months after surgery are manifested by using these parameters.

Twenty six of 37 cases underwent PCNL with a single access site (70.3%) and 11 separately with multiple accesses (29.7%). When each of the poles of a kidney was considered as a surgical unit, there were 51 units. In this manner the functional change of a unit would show the surgical trauma inflicted on the poles by PCNL access.
### Risk Summary 

Published literature reports that ciprofloxacin is present in human milk following intravenous and oral administration. There is no information regarding effects of CIPRO on milk production or the breastfed infant. Because of the potential risk of serious adverse reactions in breastfed infants, including arthropathy shown in juvenile animal studies [see Use in Specific Populations (8.4), (Clinical Considerations)], for most indications a lactating woman may consider pumping and discarding breast milk during treatment with CIPRO and an additional two days (five half-lives) after the last dose. Alternatively, advise a woman that breastfeeding is not recommended during treatment with CIPRO and for an additional two days (five half-lives) after the last dose. 

However, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on CIPRO may be acceptable [see Dosage and Administration (2.2), Pediatric Use (8.4), and Clinical Studies (14.2)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CIPRO and any potential adverse effects on the breastfed child from CIPRO or from the underlying maternal condition. 

### Clinical Considerations 

Ciprofloxacin may cause intestinal flora alteration of the breastfeeding infant. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).
PURPOSE: A daphnane-type diterpene ester compound is provided to suppress melanogenesis and to prevent or treat disease caused by hyperpigmentation. CONSTITUTION: A daphnane-type diterpene ester compound is denoted by chemical formula 1. In chemical formula 1, R is -CH3 or phenyl. A composition for skin whitening contains the compound of chemical formula 1 as an active ingredient. The composition is a cosmetic composition. A pharmaceutical composition for preventing or treating diseases caused by hyperpigmentation contains the compound of chemical formula 1 as an active ingredient. The pharmaceutical composition is an external use skin formulation.
Dehydration: Administration of hypertonic diatrizoate meglumine and diatrizoate sodium solutions may lead to hypovolemia and hypotension due to fluid loss from the intestine. A 1 in 4.6 (1:4.6) dilution of diatrizoate meglumine and diatrizoate sodium yields an approximately isotonic 16.5 percent diatrizoate salts solution; less dilute solutions are hypertonic and may lead to intraluminal movement of fluid with resulting hypovolemia. In young or debilitated children and in elderly cachectic persons, the loss of plasma fluid may be sufficient to cause a shock-like state. If diatrizoate meglumine and diatrizoate sodium solution is used in infants and children (under 10 kg) or in dehydrated or debilitated patients, the solution must be prepared using the specific dilutions described in DOSAGE AND ADMINISTRATION.In debilitated patients and in patients with electrolyte imbalances, postprocedural monitoring of hydration, serum osmolarity, electrolytes and clinical status is essential. In pediatric or severely debilitated patients, the maintenance of an open intravenous fluid line for rehydration may be advisable should hypotension or shock supervene. Electrolyte disturbances must be corrected prior to the administration of any hypertonic diatrizoate meglumine and diatrizoate sodium solutions.   
  
Aspiration: Aspiration of diatrizoate meglumine and diatrizoate sodium solution into the trachea and airways may result in serious pulmonary complications including, pulmonary edema, pneumonitis or death bronchial entry of any orally administered contrast medium causes a copious osmotic effusion. Therefore, avoid use of diatrizoate meglumine and diatrizoate sodium solution in patients with esophagotracheal fistula and minimize risks for pulmonary aspiration in all patients. If diatrizoate meglumine and diatrizoate   
sodium solution is given by nasogastric tube, the position of the tube in the stomach must be verified before administration.   
  
Anaphylactic reactions: Anaphylactic reactions, including fatalities, have been reported with the use of diatrizoate meglumine and diatrizoate sodium solution. Patients at increased risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to iodine, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies). Medical personnel trained in the treatment of anaphylactic reactions and the necessary drugs and medical equipment should always be readily available when diatrizoate meglumine and diatrizoate sodium solution is used.
In a 2-year carcinogenicity study conducted in rats, fentanyl was not associated with an increased incidence of tumors at subcutaneous doses up to 33 mcg/kg/day in males or 100 mcg/kg/day in females (0.16 and 0.39 times the human daily exposure obtained via the 100 mcg/hr patch based on AUC0-24h comparison). There was no evidence of mutagenicity in the Ames Salmonella mutagenicity assay, the primary rat hepatocyte unscheduled DNA synthesis assay, the BALB/c 3T3 transformation test, and the human lymphocyte and CHO chromosomal aberration in vitro assays.

The potential effects of fentanyl on male and female fertility were examined in the rat model via two separate experiments. In the male fertility study, male rats were treated with fentanyl (0, 0.025, 0.1 or 0.4 mg/kg/day) via continuous intravenous infusion for 28 days prior to mating; female rats were not treated. In the female fertility study, female rats were treated with fentanyl (0, 0.025, 0.1 or 0.4 mg/kg/day) via continuous intravenous infusion for 14 days prior to mating until day 16 of pregnancy; male rats were not treated. Analysis of fertility parameters in both studies indicated that an intravenous dose of fentanyl up to 0.4 mg/kg/day to either the male or the female alone produced no effects on fertility (this dose is approximately 1.6 times the daily human dose administered by a 100 mcg/hr patch on a mg/m2 basis). In a separate study, a single daily bolus dose of fentanyl was shown to impair fertility in rats when given in intravenous doses of 0.3 times the human dose for a period of 12 days.