Acute Toxicity Evaluation of Proliferol: A Dose-Escalating, Placebo-Controlled Study in Swine

2009 ◽  
Vol 28 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Simon Dagenais ◽  
James Wooley ◽  
Mark Hite ◽  
Robert Green ◽  
John Mayer
Keyword(s):  
Soft Tissues ◽  
Clinical Chemistry ◽  
Clinical Results ◽  
Skeletal Muscle Regeneration ◽  
Controlled Study ◽  
Miniature Swine ◽  
Clinical Observations ◽  
Urine Concentrations ◽  
The Many ◽  
Connective Tissue Repair

Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1×), medium (5×), or high (10×) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.

Acute Toxicity Evaluation of Proliferol: A Dose-Escalating, Placebo-Controlled Study in Rats

2007 ◽  
Vol 26 (5) ◽  
pp. 451-463 ◽  
Author(s):  
Simon Dagenais ◽  
John Mayer ◽  
James R. Wooley ◽  
Scott Haldeman ◽  
Mark Hite
Keyword(s):  
Acute Toxicity ◽  
Skeletal Muscle Regeneration ◽  
Controlled Study ◽  
High Dose ◽  
Normal Limits ◽  
Normal Ranges ◽  
Human Dose ◽  
Tissue Changes ◽  
Urine Concentrations ◽  
Soft Tissue Changes

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phe­nol 1.0% in aqueous solution. Despite extensive human experience with similar drugs administered by intraligamentous injection for chronic musculoskeletal disorders, little is known concerning preclinical toxicity. The purpose of this study was to assess the acute toxicity of intramuscular Proliferol in 96 (48 male, 48 female) Charles River strain rats, which were randomly assigned to low-(1×), medium- (5×), or high- (10×) dose Proliferol (derived from a human dose of 20 ml on a volume per bodyweight basis), or high-dose saline placebo. Observations included clinical observations, biochemistry, hematology, urinalysis, and full histopathology after 24 h or 14 days. There were no signs of ill health or reaction to treat­ment, and gait and body temperature were within normal limits. Biochemistry findings at 24 h included elevated aspartate aminotransferase, alanine aminotransferase, and haptoglobin; at 14 days all values were within normal ranges. Urinalysis findings at 24 h included increased urobilinogen and blood in all dose groups com­pared with placebo. Urine concentrations of phenol and lidocaine were greatest at 2 h and absent at 24 h. Histopathology findings included localized acute inflammatory soft tissue changes at the injection sites at 24 h and skeletal muscle regeneration at 14 days, which were consistent with the anticipated mechanism of action of Proliferol. There was no evidence of systemic toxicity from intra­muscular injection of Proliferol in rats at up to 10× the human dose.

Abstract 657: A New Translational Model of Hypercholesterolemia and Atherosclerosis: Effect of Statins on LDLR KO Miniature Swine

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Dale E Mais ◽  
Thomas Vihtelic ◽  
Chidozie Amuzie ◽  
Steven Denham ◽  
John R Swart ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Clinical Chemistry ◽  
Small Animal ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Wild Type ◽  
High Fat ◽  
Miniature Swine

Small animal models of atherosclerosis are commonly used in drug studies; however, the results often fail to translate into the clinic. A large animal model that more accurately reflects the human disease is needed. We recently developed a transgenic Yucatan pig model in which the LDL receptor (LDLR) gene is knocked out. Five groups of Yucatan pigs (N=4 per group), either wild type (LDLR+/+) or heterozygote (LDLR+/-) were fed a normal diet or a high fat diet for a six month period. One of the heterozygote/high fat diet groups in addition received a daily dose of a statin (atorvastatin) at 3 mg/kg. Every two weeks during the study a variety of clinical chemistry parameters were measured. At study termination, select arteries were collected, stained for lipid deposits and quantitated. In addition, sections of these arteries were prepared for immunohistochemistry to detect selected markers of macrophage infiltration into the atherosclerotic plaques. As expected, pigs fed a high fat diet gained significantly more weight at six months whether they were wild type or LDLR+/-. Atorvastatin appeared to attenuate this weight gain. There were significant increases in total cholesterol, HDL and LDL in pigs fed the high fat diet compared to their corresponding control group. The group receiving the atorvastatin had reduced values of these parameters compared to controls showing that a statin had a beneficial effect on lipid levels even in a high fat diet scenario. VLDL levels were not affected but there were triglyceride changes across the groups. Liver function was unchanged based on total bilirubin and AST while ALT measurements were altered in some of the groups. Immunohistochemistry and histomorphometry was performed on some arteries. Atorvastatin-induced amelioration of hypercholesterolemia in this model underscores its translational utility.

OXYGEN ADMINISTRATION AND RETROLENTAL FIBROPLASIA

PEDIATRICS ◽  
1954 ◽  
Vol 14 (5) ◽  
pp. 543-546
Author(s):  
HARRY H. GORDON
Keyword(s):  
New York ◽  
Original Description ◽  
Conclusive Evidence ◽  
Controlled Study ◽  
Low Oxygen ◽  
Retrolental Fibroplasia ◽  
Epidemiologic Survey ◽  
Oxygen Administration ◽  
Clinical Observations ◽  
Second Year

THE ORIGINAL description by the Owens of the clinical evolution of the lesions of retrolental fibroplasia stimulated a wide search for a postnatal cause. Conclusive evidence that the administration of oxygen is the major cause has been reviewed. This editorial comment is prompted by the confusion about translating the evidence into Practice. The data proving the importance of administration of oxygen consist of both clinical and laboratory observations. In 1952 Patz, Hoeck and de la Cruz reported a series of careful, controlled clinical observations from the District of Columbia General Hospital. Alternate infants weighing less than 3.5 pounds at birth were assigned to high or low oxygen and followed with careful ophthalmoscopic examinations for at least 6 months. Oxygen concentrations were measured 3 times daily and flows adjusted to maintain the desired concentrations. In a group of 28 infants kept in 65 to 70% oxygen for 4 to 7 weeks, seven or 25% showed permanent residua which included detachment of the retina. In 37 infants who received minimal oxygen, never more than 40%, from 1 day to 2 weeks, none developed residual changes. During a second year of alternation, these results were confirmed: of a total of 60 infants in high oxygen, 12 showed residua as compared with 1 in low oxygen. These clinical studies have been supported by independent uncontrolled studies from Australia, England, Switzerland, Denver, and Montreal, a more recent controlled study from New York, and an epidemiologic survey in Maryland; they bear out the original suggestion of Kinsey and Zacharias, that increased use of oxygen was one of the changes in care of premature infants which might be responsible for retrolental fibroplasia.

scholarly journals Ellenőrző lista hatása a légútbiztosítás korai szövődményeire felnőttekben

2019 ◽  
Vol 160 (26) ◽  
pp. 1025-1035 ◽  
Author(s):  
Zoltán Pál Szűcs ◽  
János Farkas ◽  
Péter Schimert ◽  
Zsolt Baranyai ◽  
Elek Dinya
Keyword(s):  
Airway Management ◽  
Primary Endpoint ◽  
Soft Tissues ◽  
Controlled Study ◽  
Data Collection Sheet ◽  
Before And After ◽  
Secondary Endpoints ◽  
Short And Long Term ◽  
Prospective Controlled Study

Abstract: Introduction: Airway management is an integral part of general anaesthesia, which may lead to severe short- and long-term complications. Aim: We assessed whether the application of a checklist for the steps of airway management reduces the number of complications in our institute. Method: In our observational, prospective, controlled study we made a checklist and a data collection sheet. Each airway management was performed for one month without the checklist and then for one month in the possession of the checklist. We evaluated the outcome of airway maneuvers and the occurrence of related early complications before and after the introduction of the checklist. The primary endpoint was the incidence of unexpected difficult airway. The secondary endpoints were difficult intubation, successful first intubation, aspiration, cardiac arrest, post-induction hypotension and desaturation, soft tissues/teeth injuries. Our results were also corrected for factors that affect the risk of complications (urgency of interventions, medical experience). Results: We did not find any difference in the frequency of acute complications before the introduction of the checklist (n = 439) and during the subsequent period (n = 423). At the primary endpoint (7.29% and 6.14%), there was no substantive difference (1.15%, 95% CI: –2.26%–4.56%, p = 0.5). No differences were found regarding the secondary and other endpoints. Following the correction of risk factors, there was no impact of the checklist on the incidence of complications. Conclusion: The introduction of the checklist in itself did not result in a significant change in the risk of short-term complications of airway management in our institution. Orv Hetil. 2019; 160(26): 1025–1035.

Combination Chemiotherapy with 5-(3,3 dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC; NSC-45388), 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU; NSC-409962) and Vincristine (VCR; NSC - 67574) in Metastatic Malignant Melanoma

1973 ◽  
Vol 59 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Gianni Beretta ◽  
Emilio Bajetta ◽  
Gianni Bonadonna ◽  
Gabriele Tancini ◽  
Sergio Orefice ◽  
...  
Keyword(s):  
Side Effects ◽  
Malignant Melanoma ◽  
Complete Remission ◽  
Soft Tissues ◽  
Average Duration ◽  
Metastatic Malignant Melanoma ◽  
Controlled Study ◽  
Bone Lesions ◽  
Therapeutic Effects ◽  
Males And Females

The toxic and therapeutic effects obtained with a triple drug combination (BCNU, DTIC and VCR) administered in a cyclic fashion to 41 unselected evaluable patients with metastatic malignant melanoma are reported. Side effects were moderate and reversible. The overall regression rate was 44% without difference between males and females. Partial remission (> 50%) plus complete remission was 19.5% with an average duration of 5.1 months (1–20+). With the exclusion of bone lesions, all types of metastases showed regression especially those located in the soft tissues (lymph nodes and skin). The actuarial analysis of survival shows that responders live twice as long as non responders (median survival 12 months versus 6 months). However, the superior therapeutic efficacy of BCNU + DTIC + VCR over DTIC alone in metastatic melanoma remains to be demonstrated. A controlled study with different triple combinations is now in progress.

scholarly journals Reducing Nasopharyngeal Trauma: The Urethral Catheter–Assisted Nasotracheal Intubation Technique

2011 ◽  
Vol 58 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Allen Wong ◽  
Paul Subar ◽  
Heidi Witherell ◽  
Konstantin J Ovodov
Keyword(s):  
Soft Tissues ◽  
Nasotracheal Intubation ◽  
Mouth Opening ◽  
Urethral Catheter ◽  
Alternative Methods ◽  
Nasal Intubation ◽  
Intubation Technique ◽  
Invasive Approach ◽  
Dental Procedures ◽  
The Many

Nasal intubation is an advantageous approach for dental procedures performed in the hospital, ambulatory surgery center, or dental office, when possible. Although many who provide anesthesia services are familiar and comfortable with nasal intubation techniques, some are reluctant and uncomfortable because of lack of experience or fear of nasopharyngeal bleeding and trauma. It has been observed from experiences in various settings that many approaches may be adapted to the technique of achieving nasal intubation. The technique that is described in this paper suggests a minimally invasive approach that introduces the nasoendotracheal tube through the nasopharyngeal pathway to the oropharynx in an expedient manner while preserving the nasopharyngeal structures, thus lessening nasal bleeding and trauma to soft tissues. The technique uses a common urethral catheter and can be incorporated along with current intubation armamentaria. As with all techniques, some limitations to the approach have been identified and are described in this paper. Cases with limited mouth opening, neck injury, and difficult airways may necessitate alternative methods. However, the short learning curve along with the many benefits of this technique offers the anesthesia professional additional options for excellent patient care.

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