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Theriogenology Nov 2012The impact of successful cryopreservation of spermatozoa can be found in many fields, including agriculture, laboratory animal medicine, and human assisted reproduction,...
The impact of successful cryopreservation of spermatozoa can be found in many fields, including agriculture, laboratory animal medicine, and human assisted reproduction, providing a cost-effective and efficient method to preserve genetic material for decades. The success of any cryobiologic protocol depends critically on understanding the fundamentals that underlie the process. In this review, we summarize the biophysical fundamentals critical to much of the research in sperm cryobiology, provide a synopsis of the development of sperm cryobiology as a discipline, and present the current state and directions for future research in sperm cryobiology in the three major areas outlined above-agriculture, laboratory animal medicine, and human clinical assisted reproduction. There is much room for new research, both empiric and fundamental, in all areas, including refinement of mathematical models, optimization of cryoprotective agent addition and removal procedures for spermatozoa from many species, development of effective, efficient, and facile cryopreservation protocols and freezing containers for agricultural sperm cryopreservation, and tailoring cryopreservation protocols for individual human samples.
Topics: Agriculture; Animals; Animals, Laboratory; Aquaculture; Cryopreservation; Cryoprotective Agents; Humans; Male; Mice; Models, Theoretical; Osmosis; Reproductive Techniques, Assisted; Semen Preservation; Spermatozoa; Swine
PubMed: 23062722
DOI: 10.1016/j.theriogenology.2012.06.007 -
Oral Surgery, Oral Medicine, Oral... Nov 2010The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA).
STUDY DESIGN
Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model.
RESULTS
Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively.
CONCLUSIONS
The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.
Topics: Acyclovir; Administration, Topical; Adult; Antifungal Agents; Antineoplastic Agents, Phytogenic; Antiviral Agents; Candidiasis, Oral; Double-Blind Method; Female; Follow-Up Studies; Guanine; HIV Infections; HIV Seropositivity; Heterosexuality; Humans; Leukoplakia, Hairy; Male; Middle Aged; Neoplasm Recurrence, Local; Podophyllin; Proportional Hazards Models; Remission Induction; Time Factors; Tongue Neoplasms; Treatment Outcome; Young Adult
PubMed: 20813564
DOI: 10.1016/j.tripleo.2010.05.015 -
The Western Journal of Emergency... Oct 2019The management of sepsis includes the prompt administration of intravenous antibiotics. There is concern that sepsis treatment protocols may be inaccurate in identifying...
INTRODUCTION
The management of sepsis includes the prompt administration of intravenous antibiotics. There is concern that sepsis treatment protocols may be inaccurate in identifying true sepsis and exposing patients to potentially harmful antibiotics, sometimes unnecessarily. This study was designed to investigate those concerns by focusing on in-hospital Clostridium difficile infection (CDI), which is a known complication of exposure to antibiotics.
METHODS
Our emergency department (ED) recently implemented a protocol to help combat sepsis and increase compliance with the 2017 Sepsis CMS Core Measures (SEP-1) guidelines. In this single-center, retrospective cohort analysis we queried the electronic health record to gather data on nosocomial CDI and antibiotics prescribed over a five-year period to analyze the effect of the introduction of a sepsis protocol order set. The primary goal of this study was to measure the hospital-wide CDI rate for three years prior to implementation of the sepsis bundle, and then compare this to the hospital-wide CDI rate two years post-implementation. As a secondary outcome, we compared the number of antibiotics prescribed in the ED 12 months prior to administration of the sepsis protocol vs 12 months post-initiation.
RESULTS
Over the course of five years, the hospital averaged 9.4 nosocomial CDIs per 10,000 patient hours. Prior to implementation of the sepsis bundle, the average CDI rate was 11.6 (±1.11, 95%) and after implementation the average rate dropped to 6.2 (±1.27, 95%, p<0.01). The mean number of antibiotics ordered per patient visit was 0.33 (±0.015, 95%) prior to bundle activation, and, following sepsis bundle activation, the rate was 0.38 (±0.019, 95%, p<0.01). This accounted for 38% of all ED patient visits receiving antibiotics, a 5% increase after the sepsis bundle was introduced.
CONCLUSION
In this study, we found that CDI infections declined after implementation of a sepsis bundle. There was, however an increase in the number of patients being exposed to antibiotics after this hospital policy change. There are more risks than just CDI with antibiotic exposure, and these were not measured in this study. Subsequent studies should focus on the ongoing effects of timed, protocolized care and the associated risks.
Topics: Anti-Bacterial Agents; Clinical Protocols; Clostridium Infections; Emergency Service, Hospital; Humans; Incidence; Retrospective Studies; Sepsis
PubMed: 31738730
DOI: 10.5811/westjem.2019.10.42070 -
Pharmacotherapy Jun 2017Induction immunosuppression significantly improves graft outcomes after kidney transplantation, but protocols vary among transplant centers due to the lack of data...
STUDY OBJECTIVE
Induction immunosuppression significantly improves graft outcomes after kidney transplantation, but protocols vary among transplant centers due to the lack of data identifying an optimal induction agent. The objective of this study was to assess the effectiveness of an evidence-based protocol change in induction therapy in adult kidney transplant recipients.
DESIGN
Retrospective cohort study.
SETTING
Large tertiary care academic medical center.
PATIENTS
A total of 349 patients transplanted between August 2011 and December 2013 were included in the study. A protocol revision in 2012 reserved the use of lymphocyte-depleting induction therapy to a select group of traditionally high-risk patients based on the findings of a previous randomized controlled trial performed at this center.
MEASUREMENTS AND MAIN RESULTS
The primary outcome was biopsy-proved acute rejection and graft loss. The use of nondepleting induction therapy increased significantly after the protocol revision, with no significant differences in rejection or infection rates identified between protocols. When comparing graft survival between the protocol cohorts, there was no significant difference. A cost-minimization analysis indicated that the revised protocol was associated with considerable medication cost savings.
CONCLUSION
A protocol targeting the use of lymphocyte-depleting induction to a select group of high-risk recipients appears to have equivalent efficacy and safety and is less costly compared with a more traditional induction protocol.
Topics: Adult; Clinical Protocols; Cohort Studies; Evidence-Based Medicine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Induction Chemotherapy; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Transplant Recipients; Treatment Outcome
PubMed: 28475248
DOI: 10.1002/phar.1941 -
AJR. American Journal of Roentgenology May 2016The objective of our study was to compare a flavored beverage containing a thickening agent for enterography with a low-Hounsfield-value barium suspension for side... (Clinical Trial)
Clinical Trial
OBJECTIVE
The objective of our study was to compare a flavored beverage containing a thickening agent for enterography with a low-Hounsfield-value barium suspension for side effects, taste, subjects' willingness to repeat the drinking protocol, and small-bowel distention.
SUBJECTS AND METHODS
The following five drinking protocols were administered to 10 volunteers: 1000 mL of flavored beverage followed by 350 mL of water, 1500 mL of flavored beverage, 900 mL of low-Hounsfield-value barium suspension followed by 450 mL of water, 1350 mL of low-Hounsfield-value barium suspension followed by 150 mL of water, and 1500 mL of water. MR images were obtained 50 and 60 minutes after initiation of drinking. Subjects completed a questionnaire evaluating the side effects, the taste of the drink, and their willingness to repeat the drinking protocol. Reviewers assigned scores evaluating small-bowel distention and ranked the examinations in order of preference.
RESULTS
There was no significant difference in nausea or vomiting among the protocols (p = 0.20 and 0.42, respectively), but larger volumes of flavored beverage and low-Hounsfield-value barium suspension resulted in more cramping and diarrhea (p = 0.001 and 0.002, respectively). The taste of the low-Hounsfield-value barium suspension was rated the worst (p < 0.0001). The subjects' willingness to repeat the drinking protocol was highest for the 1000 mL of flavored beverage or water alone (p < 0.05). There were no significant differences in subjective small-bowel distention except that water was rated the worst by two of the three readers (p < 0.02). There was no significant difference in the diameter of the most dis-tended small bowel for any segment or reader (p > 0.23).
CONCLUSION
A flavored beverage containing a thickening agent has a similar side effect profile and results in equivalent small-bowel distention compared with a low-Hounsfield-value barium suspension, but subjects rate taste and their willingness to repeat the drinking protocol higher for this new agent.
Topics: Administration, Oral; Adult; Barium Sulfate; Contrast Media; Diagnostic Techniques, Digestive System; Dilatation; Female; Flavoring Agents; Humans; Intestine, Small; Male; Patient Preference; Prospective Studies; Young Adult
PubMed: 26998661
DOI: 10.2214/AJR.15.15260 -
Cryobiology Dec 2022Vitrification can extend the banking life of articular cartilage (AC) and improve osteochondral transplantation success. Current vitrification protocols require...
Vitrification can extend the banking life of articular cartilage (AC) and improve osteochondral transplantation success. Current vitrification protocols require optimization to enable them to be implemented in clinical practice. Sucrose as a non-permeating cryoprotective agent (CPA) and clinical grade chondroitin sulfate (CS) and ascorbic acid (AA) as antioxidants were investigated for their ability to improve a current vitrification protocol for AC. The aim of this study was to assess the impact of sucrose and CS/AA supplementation on post-warming chondrocyte viability in vitrified AC. Porcine osteochondral dowels were randomly vitrified and warmed with one established protocol (Protocol 1) and seven modified protocols (Protocols 2-8) followed by chondrocyte viability assessment. Sucrose supplementation in both vitrification and warming media (Protocol 4) resulted in significantly higher (p = 0.018) post-warming chondrocyte viability compared to the protocol without sucrose (Protocol 1). There was no significant difference (p = 0.298) in terms of post-warming chondrocyte viability between sucrose-supplemented DMEM + CS solution (Protocol 4) and Unisol-CV (UCV) + CS (Protocol 6) solution. Clinical grade CS and AA contributed to similar post-warming chondrocyte viability to previous studies using research grade CS and AA, indicating their suitability for clinical use. The addition of an initial step (step 0) to reduce the initial concentration of CPAs to minimize osmotic effects did not enhance chondrocyte viability in the superficial layer of AC. In conclusion, sucrose-supplemented DMEM + clinical grade CS (Protocol 4) could be an ideal protocol to be investigated for future use in clinical applications involving vitrified AC.
Topics: Swine; Animals; Vitrification; Chondrocytes; Cartilage, Articular; Cryopreservation; Cryoprotective Agents; Sucrose; Ascorbic Acid; Chondroitin Sulfates; Dietary Supplements
PubMed: 36155184
DOI: 10.1016/j.cryobiol.2022.09.004 -
Current Topics in Medicinal Chemistry 2012Combining several cytotoxics is the current mainstay for treating breast cancer patients. The combination between capecitabine and docetaxel was found to be more...
Combining several cytotoxics is the current mainstay for treating breast cancer patients. The combination between capecitabine and docetaxel was found to be more efficient than capecitabine or docetaxel when both were used as single agents. However, the administration protocol for this combination has been empirically chosen from single-agent trials. Based on already available population analysis, we propose here to optimize the administration protocol of this association so as to enhance efficacy while limiting treatment-related toxicity. Efficacy parameters evaluated from population analysis using a disturbed tumor growth model and safety characteristics from the available databases evidenced that: 1) Docetaxel is more efficient than capecitabine at the start of the treatment, but becomes less efficient next because of acquisition of resistance; 2) Over a long period of time, capecitabine is better tolerated than docetaxel. These characteristics allowed the following recommendations for an optimized modality of combination: 1) The treatment has to be started at the maximum tolerated dose for docetaxel; this dose should be individualized right from the start of the second cycle of treatment; 2) In parallel, capecitabine has to be started at a dose lower than its maximum tolerated dose. 3) When docetaxel becomes less efficient than capecitabine because of resistance, docetaxel dose has to be reduced but not discontinued. 4) If adverse events show during the treatment, it is recommended to reduce docetaxel, rather than capecitabine dosage. Combining modeling and statistical analysis of clinical data permit to optimize combination treatments. This procedure could be extended to others treatments involving combination of several cytotoxics.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Databases as Topic; Deoxycytidine; Docetaxel; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Maximum Tolerated Dose; Models, Statistical; Neoplasm Metastasis; Taxoids; Treatment Outcome
PubMed: 22978334
DOI: 10.2174/156802612803531306 -
Human Reproduction (Oxford, England) Apr 2014What is the optimal vitrification protocol according to the cryoprotective agent (CPA) for ovarian tissue (OT) cryopreservation?
Optimal vitrification protocol for mouse ovarian tissue cryopreservation: effect of cryoprotective agents and in vitro culture on vitrified-warmed ovarian tissue survival.
STUDY QUESTION
What is the optimal vitrification protocol according to the cryoprotective agent (CPA) for ovarian tissue (OT) cryopreservation?
SUMMARY ANSWER
The two-step protocol with 7.5% ethylene glycol (EG) and 7.5% dimethyl sulfoxide (DMSO) for 10 min then 20% EG, 20% DMSO and 0.5 M sucrose for 5 min showed the best results in mouse OT vitrification.
WHAT IS KNOWN ALREADY
Establishing the optimal cryopreservation protocol is one of the most important steps to improve OT survival. However, only a few studies have compared vitrification protocols with different CPAs and investigated the effect of in vitro culture (IVC) on vitrified-warmed OT survival. Some recent papers proposed that a combination of CPAs has less toxicity than one type of CPA. However, the efficacy of different types and concentrations of CPA are not yet well documented.
STUDY DESIGN, SIZE, DURATION
A total of 644 ovaries were collected from 4-week-old BDF1 mice, of which 571 ovaries were randomly assigned to 8 groups and vitrified using different protocols according to CPA composition and the remaining 73 ovaries were used as controls. After warming, each of the eight groups of ovaries was further randomly divided into four subgroups and in vitro cultured for 0, 0.5, 2 and 4 h, respectively. Ovaries of the best two groups among the eight groups were autotransplanted after IVC.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The CPA solutions for the eight groups were composed of EDS, ES, ED, EPS, EF, EFS, E and EP, respectively (E, EG; D, DMSO; P, propanediol; S, sucrose; F, Ficoll). The IVC medium was composed of α-minimal essential medium, 10% fetal bovine serum and 10 mIU/ml follicle-stimulating hormone (FSH). Autotransplantation of vitrified-warmed OTs after IVC (0 to 4 h) using the EDS or ES protocol was performed, and the grafts were recovered after 3 weeks. Ovarian follicles were assessed for morphology, apoptosis, proliferation and FSH level.
MAIN RESULTS AND THE ROLE OF CHANCE
The percentages of the morphologically intact (G1) and apoptotic follicles in each group at 0, 0.5, 2 and 4 h of IVC were compared. For G1 follicles at 0 and 4 h of IVC, the EDS group showed the best results at 63.8 and 46.6%, respectively, whereas the EP group showed the worst results at 42.2 and 12.8%, respectively. The apoptotic follicle ratio was lowest in the EDS group at 0 h (8.1%) and 0.5 h (12.7%) of IVC. All of the eight groups showed significant decreases in G1 follicles and increases in apoptotic follicles as IVC duration progressed. After autotransplantation, the EDS 0 h group showed a significantly higher G1 percentage (84.9%) than did the other groups (42.4-58.8%), while only the ES 4 h group showed a significant decrease in the number of proliferative cells (80.6%, 87.6-92.9%). However, no significant differences in apoptotic rates and FSH levels were observed between the groups after autotransplantation.
LIMITATIONS, REASONS FOR CAUTION
The limitation of this study was the absence of in vitro fertilization using oocytes obtained from OT grafts, which should be performed to confirm the outcomes of ovarian cryopreservation and transplantation.
WIDER IMPLICATIONS OF THE FINDINGS
We compared eight vitrification protocols according to CPA composition and found the EDS protocol to be the optimal method among them. The data presented herein will help improve OT cryopreservation protocols for humans or other animals.
Topics: Animals; Apoptosis; Cell Proliferation; Cryopreservation; Cryoprotective Agents; Female; Follicle Stimulating Hormone; Mice; Mice, Inbred Strains; Ovary; Vitrification
PubMed: 24365801
DOI: 10.1093/humrep/det449 -
Critical Care (London, England) 2010Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not... (Review)
Review
Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.
Topics: Cardiac Surgical Procedures; Heart Failure; Humans; Perioperative Care; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis
PubMed: 20497611
DOI: 10.1186/cc8153 -
Journal of the Egyptian National Cancer... Jun 2022The therapy design of childhood acute lymphoblastic leukemia (ALL) has evolved over the past 60 years. The St. Jude Children's Research Hospital has developed 17... (Review)
Review
The therapy design of childhood acute lymphoblastic leukemia (ALL) has evolved over the past 60 years. The St. Jude Children's Research Hospital has developed 17 treatment protocols from 1962 to 2017, aiming to have the most effective and least toxic treatment form. This review summarizes each protocol's objectives, inclusion criteria, treatment phases, pharmacological agents, irradiation therapy, response criteria, risk stratification, type of relapse, and overall survival. The enhancement and successful application of preventive therapy for ALL and following a risk-stratified approach have progressively improved the cure rate of childhood ALL, with relatively few adverse sequelae. Moreover, St. Jude's scientific theme serves as a reminder of the principal factor of research directed to a catastrophic disease such as ALL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Hospitals, Pediatric; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 35696003
DOI: 10.1186/s43046-022-00126-3