1) The study examined nasal lesion distribution patterns in rats from one inhalation study, two drinking water studies, and three gavage studies conducted by the NTP.
2) Nasal lesions from the inhalation study were predominantly bilateral, dorsal, and located in the anterior nasal sections. Lesions from the drinking water studies were uniformly located in the middle and posterior nasal sections and affected only the olfactory epithelium.
3) Nasal lesions from the gavage studies varied in character and distribution, tended to be more posterior and ventral, and were predominantly unilateral. Lesions in the nasopharyngeal duct only occurred in the gavage studies.
4) Differences in nasal lesion distribution provide clues
This document studied the nasal parameters of two ethnic groups in southern Nigeria - the Ibibio and Yakurr peoples. It measured the nasal length, width and index of 400 subjects (200 from each group, split evenly between males and females). The results found significant differences in the nasal parameters between genders within each ethnic group, and between the two ethnic groups. Based on nasal index, the study classified nose shapes as platyrrhine or mesorrhine. It concluded that nasal parameters can be useful for distinguishing gender and ethnicity between these groups.
This document discusses oral malodour (bad breath). It begins by defining oral malodour and noting its various synonyms. It then classifies oral malodour into genuine, physiological, pathological, pseudo, and halitophobia categories. The document outlines intraoral and extraoral causes of oral malodour and describes methods for diagnosis, including medical history, examination, and laboratory tests. Key diagnostic tests mentioned are organoleptic rating, portable sulfide monitors, and BANA testing. The document concludes by discussing treatments for oral malodour which include mechanical reduction of substrates, chemical reduction of microorganisms, conversion of volatile sulfur compounds, and masking of malodour.
Breath malodor has important socioeconomic consequences and can reveal important diseases. A proper diagnosis and determination of the etiology allow initiation of the proper etiologic treatment.
ABSTRACT- Mosquitoes are important groups of arthropods that inhabit freshwater habitats. The distribution pattern
of adult mosquitoes is related to habitat preference of the immature stages. These habitats may be natural or man-made
and temporary or permanent. Mosquitoes are carriers of number of diseases; mostly in the tropics, causing illness and
death on a large scale. The survey was carried out during June 2015 to May 2016 from different ten villages of
Kopargaon teshil (M.S.). Mosquito larvae were collected at different habitats, these are temporary and permanent,
larvae collections were carried out regular month wise. A total 3627 mosquito larvae were collected of which were
density of Culicinae were 90.21% and Anophelinae were 9.79%. During the study period seven mosquito species were
identified, which are Anopheles stephensi, Culex vishnui, Culex pseudovishnui, Culex quinquefasciatus, Aedes aegypti,
Aedes albopictus and Armigeres subalbatus. Their densities are Anopheles stephensi 9.79%, Culex vishnui 13.51%,
Culex pseudovishnui 10.34%, Culex quinquefasciatus 7.2%, Aedes aegypti 26.16%, Aedes albopictus 15.08% and
Armigeres subalbatus 17.92% respectively. The mosquito larval fauna providing primary checklist of mosquito vector
diversity from study area.
Key-words- Larval habitat, Density, Vector mosquitoes, Anopheles stephensi, Culex quinquefasciatus, Aedes aegypti,
Aedes albopictus
The main purpose of a Pathology Peer Review is to improve the quality of the pathology data and narrative. This can be achieved in several ways. A peer review can help to ensure that the data are presented in a manner that meets the requirements of the regulatory agency to which the data will be submitted. A peer review may help to increase the accuracy of the data, thus increasing the confidence in it both for the Sponsor and for the regulatory agencies. This is true whether the study was completed at the Sponsor’s facility, at a Contract Research Organization (CRO), or in an academic laboratory. A peer review can also confirm the target organs identified in the original evaluation and confirm the No Observed Effect Level (NOEL). Our unique PQA software program is a computerized pathology peer review procedure developed at EPL that operates on a portable laptop computer. Study data can be interfaced between the laboratory and EPL’s pathology peer review program through the use of electronic ASCII text files. This assures that the accuracy of the data is maintained during the entire review process and that comparison between the preliminary histopathology data from the laboratory and the pathology quality assurance audit can be made rapidly. In this manner, differences can be easily identified and resolved by the study pathologist and reviewing pathologist, thus allowing the laboratory to complete the draft study report in a timely manner.
Peer review also serves as a source of continuing education and training, for both the study pathologist and the reviewing pathologist. In many cases the study pathologist will have a limited amount of experience, and can benefit from the broader range of experience of the reviewing pathologist. On the other hand, the reviewing pathologist almost always sees something new and learns something different during every peer review. EPL’s team of experienced pathologists have been providing peer review services to the NCI/NTP carcinogenesis testing program and commercially for companies in the pharmaceutical, biotechnology and chemical industry for over 30 years. We provide these services to clients in North America, Europe and Asia. When conducting a peer review, we take our team to the testing laboratory where the study pathologist is located. This eliminates the cost and risk associate with shipping the glass microscope slides and by working directly with the study pathologist to finalize the findings speeds up the reporting process.
This document studied the nasal parameters of two ethnic groups in southern Nigeria - the Ibibio and Yakurr peoples. It measured the nasal length, width and index of 400 subjects (200 from each group, split evenly between males and females). The results found significant differences in the nasal parameters between genders within each ethnic group, and between the two ethnic groups. Based on nasal index, the study classified nose shapes as platyrrhine or mesorrhine. It concluded that nasal parameters can be useful for distinguishing gender and ethnicity between these groups.
This document discusses oral malodour (bad breath). It begins by defining oral malodour and noting its various synonyms. It then classifies oral malodour into genuine, physiological, pathological, pseudo, and halitophobia categories. The document outlines intraoral and extraoral causes of oral malodour and describes methods for diagnosis, including medical history, examination, and laboratory tests. Key diagnostic tests mentioned are organoleptic rating, portable sulfide monitors, and BANA testing. The document concludes by discussing treatments for oral malodour which include mechanical reduction of substrates, chemical reduction of microorganisms, conversion of volatile sulfur compounds, and masking of malodour.
Breath malodor has important socioeconomic consequences and can reveal important diseases. A proper diagnosis and determination of the etiology allow initiation of the proper etiologic treatment.
ABSTRACT- Mosquitoes are important groups of arthropods that inhabit freshwater habitats. The distribution pattern
of adult mosquitoes is related to habitat preference of the immature stages. These habitats may be natural or man-made
and temporary or permanent. Mosquitoes are carriers of number of diseases; mostly in the tropics, causing illness and
death on a large scale. The survey was carried out during June 2015 to May 2016 from different ten villages of
Kopargaon teshil (M.S.). Mosquito larvae were collected at different habitats, these are temporary and permanent,
larvae collections were carried out regular month wise. A total 3627 mosquito larvae were collected of which were
density of Culicinae were 90.21% and Anophelinae were 9.79%. During the study period seven mosquito species were
identified, which are Anopheles stephensi, Culex vishnui, Culex pseudovishnui, Culex quinquefasciatus, Aedes aegypti,
Aedes albopictus and Armigeres subalbatus. Their densities are Anopheles stephensi 9.79%, Culex vishnui 13.51%,
Culex pseudovishnui 10.34%, Culex quinquefasciatus 7.2%, Aedes aegypti 26.16%, Aedes albopictus 15.08% and
Armigeres subalbatus 17.92% respectively. The mosquito larval fauna providing primary checklist of mosquito vector
diversity from study area.
Key-words- Larval habitat, Density, Vector mosquitoes, Anopheles stephensi, Culex quinquefasciatus, Aedes aegypti,
Aedes albopictus
The main purpose of a Pathology Peer Review is to improve the quality of the pathology data and narrative. This can be achieved in several ways. A peer review can help to ensure that the data are presented in a manner that meets the requirements of the regulatory agency to which the data will be submitted. A peer review may help to increase the accuracy of the data, thus increasing the confidence in it both for the Sponsor and for the regulatory agencies. This is true whether the study was completed at the Sponsor’s facility, at a Contract Research Organization (CRO), or in an academic laboratory. A peer review can also confirm the target organs identified in the original evaluation and confirm the No Observed Effect Level (NOEL). Our unique PQA software program is a computerized pathology peer review procedure developed at EPL that operates on a portable laptop computer. Study data can be interfaced between the laboratory and EPL’s pathology peer review program through the use of electronic ASCII text files. This assures that the accuracy of the data is maintained during the entire review process and that comparison between the preliminary histopathology data from the laboratory and the pathology quality assurance audit can be made rapidly. In this manner, differences can be easily identified and resolved by the study pathologist and reviewing pathologist, thus allowing the laboratory to complete the draft study report in a timely manner.
Peer review also serves as a source of continuing education and training, for both the study pathologist and the reviewing pathologist. In many cases the study pathologist will have a limited amount of experience, and can benefit from the broader range of experience of the reviewing pathologist. On the other hand, the reviewing pathologist almost always sees something new and learns something different during every peer review. EPL’s team of experienced pathologists have been providing peer review services to the NCI/NTP carcinogenesis testing program and commercially for companies in the pharmaceutical, biotechnology and chemical industry for over 30 years. We provide these services to clients in North America, Europe and Asia. When conducting a peer review, we take our team to the testing laboratory where the study pathologist is located. This eliminates the cost and risk associate with shipping the glass microscope slides and by working directly with the study pathologist to finalize the findings speeds up the reporting process.
Protocol Design and Recruitment StrategyGregg Sweet
1) Recruitment strategy should be developed during protocol design rather than waiting until after protocol completion and site selection. Starting recruitment planning early increases the chances of enrollment success.
2) Marketing support is usually necessary for clinical trials as relying solely on investigators and sites often leads to under-enrollment. Integrated marketing programs are needed to create awareness of trials.
3) Recruitment support should involve a cohesive, organized strategy with consistent messaging across sites and tactics, rather than leaving recruitment planning to individual sites. Specialized recruitment professionals usually have better marketing skills than clinical staff.
VL Presentation: Managing Protocol Deviation using Authorization CodesVeracity Logic, LLC
The document discusses how Veracity Logic's Interactive Response Technology (VLIRT) can be used to manage protocol deviations using authorization codes. It describes setting up authorization codes to be used for subjects outside an age range or for recording activity outside a predefined window. It shows how the system prompts for an authorization code in these situations and generates a report afterward listing the codes used, subjects, and reasons. Contact information is provided for any questions.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise stimulates the production of endorphins in the brain which elevate mood and reduce stress levels.
El documento describe diferentes tipos de mundos literarios, incluyendo mundos cotidianos que representan nuestro mundo realista, mundos míticos que contienen relatos orales de hechos fabulosos del pasado, y mundos oníricos que representan los sueños a través de la narrativa subjetiva. También describe mundos según el efecto perseguido, como mundos realistas que buscan reflejar la realidad de manera objetiva, mundos fantásticos que provocan enigmas sobre la naturaleza del mundo, y mundos utópicos que
El documento define el medio ambiente como todo lo que rodea a un ser vivo, incluyendo seres vivos, objetos, agua, suelo, aire y sus interacciones, así como elementos culturales. Explica que el medio ambiente comprende los valores naturales, sociales y culturales de un lugar y tiempo que influyen en la vida humana y futuras generaciones. Además, describe el origen etimológico de las palabras "medio" y "ambiente" del latín.
Parminder Jhaj is seeking a full-time position in information systems, analytics, or IT operations utilizing their analytical and problem-solving skills. They graduated from the University of Illinois at Chicago with a Bachelor of Science in Information & Decision Sciences and a 3.8 GPA. Relevant experience includes gathering requirements for an SDLC restaurant automation project and creating a website and ATM simulator using programming languages. Additional skills include Microsoft Office, databases, project management, digital marketing, and information security.
This document is a resume for Aricka Marshall providing her contact information, objective, skills, education, and work experience. She has over 10 years of experience in retail, customer service, assembly, and warehouse roles. Her most recent positions include office manager, house keeper, and various temp roles in machining, assembly, and receiving. She aims to utilize her experiences and skills like attention to detail, teamwork, and computer skills to provide quality customer service.
Geotourism Means Accessible & InclusiveScott Rains
The document provides a list of questions for geotourism projects to consider regarding inclusiveness for travelers with disabilities. It asks if information is provided in accessible formats, if websites follow accessibility standards, if activities can be inclusive of all abilities, if marketing portrays people with disabilities respectfully, if employees with disabilities are hired in mainstream roles, and if universal design principles are followed to ensure accessibility for all. The questions also address legal obligations under the UN Convention on Rights of Persons with Disabilities and how sustainable tourism criteria can enhance experiences for travelers, employees and local residents with disabilities.
In the Bible, Colossians 2:8 reads – “Beware lest any man take you captive through vain and deceitful philosophy, after the tradition of men, after the rudiments of the world, and not after Christ.” Since Darwin published his book of Origins 150 years ago, civilization has been on a dangerous journey of replacing God and His creation of the Universe, with what the Bible calls the “vain and deceitful” philosophies of men. These men…and women….. have been teachers, politicians, rock stars, news anchors, even some pastors and preachers. Those philosophies are evolution, naturalism, humanism, Nazism, Marxism, socialism, etc.. These philosophies have led to the social diseases of racism, abortion, eugenics, materialism, and more......
Comunicado Venezuela contra injerencia de Luis AlmagroteleSUR TV
El Gobierno de Venezuela repudió este martes el "ilegítimo e ilícito pretendido informe sobre Venezuela" presentado por el secretario general de la Organización de Estados Americanos (OEA), Luis Almagro, que promueve una intervención extranjera.
This document summarizes a study that investigated sex-based differences in bronchiolar epithelial injury and repair following naphthalene inhalation in rats. The key points are:
1) Male and female rats were exposed to naphthalene vapor and sacrificed at various time points to assess injury and regeneration of bronchiolar epithelium.
2) Naphthalene exposure induced bronchiolar cell exfoliation peaking at 24 hours in both sexes. Male epithelium fully regenerated by 14 days, while females still had some exfoliated cells at 14 days that disappeared by 21 days.
3) Injury occurred earlier and involved more cells in females, while regeneration occurred earlier in males
Nasal drug delivery provides direct access to the systemic circulation while avoiding first-pass metabolism and potential degradation in the gastrointestinal tract. The nasal cavity has a large surface area and highly vascularized nasal mucosa that allows for rapid drug absorption. Various nasal drug formulations have been developed, including sprays, gels, and powders, to enhance drug retention and absorption in the nasal cavity. The nasal route is promising for local and systemic delivery of peptides, proteins, and central nervous system targeting of drugs.
—Fungal organisms are ubiquitous. A common location for these organisms to enter the human body is through the external acoustic canal, oral cavity, and pharynx and sino-nasal cavity. A study was conducted with clinical and mycological analysis of various fungal infections in ENT. Patients suspected for having fungal infections attending at Department of ENT were interrogated and analysed. Swabs collected from these cases were sent for direct microscopy by KOH mounts for fungal examination and fungal culture. Microbiological confirmed 100 cases were finally included in the study Histopathological examination of nasal mass and polyposis was also done. It was observed in this present study otomycosis was most common and accounted for 84% of the total cases followed by candidiasis in oral cavity and pharynx in 9%, allergic fungal rhinosinusitis in 4% and rhinosporidiosis in 3%. Aspergillus niger was that most common fungus isolated in 61% cases, followed by Candida albicans in 24% cases, Aspergillus flavus in 9% cases, Aspergillus fumigatus and Rhinosporodium seeberi in 3% cases each. All the cases of fungal infection of oral cavity and oropharynx were due to Candida albicans.
1) The growth pattern and role of the tonsils and adenoids in dentofacial development are controversial topics that have been debated for many years. While enlarged tonsils and adenoids can affect breathing and dentofacial structure, the criteria for determining when surgical removal is needed are not well-defined.
2) Tonsils and adenoids play an important role in the immune system as the primary sites of exposure to antigens. However, it is unclear whether surgical removal compromises immune function. Some studies have found lower antibody levels or increased cancer risk after removal, while others have not.
3) There is ongoing debate around the benefits of tonsillectomy and adenoidectomy
This document summarizes an article by Allen J. Moses about obstructive breathing conditions and their implications for dental treatment. It describes an appliance called a "passivator" that supports the mandible in an open bite position without causing tooth movement. The document discusses how nasal obstruction can cause mouth breathing, which can lead to issues like narrow arches and abnormal swallowing. It reviews studies on monkeys that found oral breathing altered neuromuscular activity and bone structure. The most common causes of nasal obstruction in humans are also outlined.
This document provides an update to the 2006 clinical practice guideline for managing acute otitis externa (AOE). The update was needed due to new clinical trials, systematic reviews, and lack of consumer participation in the original guideline development. AOE is defined as diffuse inflammation of the external ear canal and remains a common infection. Topical antimicrobial therapy is effective for AOE but oral antibiotics are often inappropriately prescribed. The guideline makes recommendations for the diagnosis, treatment, and management of AOE with a focus on appropriate use of analgesics and topical vs. oral antimicrobials.
This document summarizes a study that analyzed the bacterial profiles of saliva samples from 292 participants with low levels of oral diseases. The study found:
1) The predominant bacteria in saliva were Streptococcus and Veillonella.
2) Differences in diet, lifestyle factors (age, gender, BMI, alcohol consumption), and diet composition did not influence bacterial profiles.
3) Smokers had higher levels of Streptococcus sobrinus and Eubacterium brachy compared to non-smokers.
4) Socioeconomic status may influence bacterial profiles, as profiles differed between high and low socioeconomic groups.
This document reviews nasal polyposis (NP), a common condition affecting up to 4% of the population. It discusses the unclear etiology of NP, associated with factors like allergy, asthma, and infection. Clinical features include nasal obstruction, anosmia, and polypoid masses visible during examination. Management involves medical therapy like corticosteroids as primary treatment and to prevent recurrence, as well as surgery for refractory cases. Recurrence is common even after treatment.
Nasal drug delivery is an alternative to oral administration that avoids first-pass metabolism and allows for rapid systemic absorption. The nasal cavity has features making it suitable for drug delivery such as a large surface area, porous epithelium, and avoidance of first-pass metabolism. Drugs are transported across the nasal epithelium through passive diffusion or active transport. Factors like particle size, molecular weight, pH, and concentration impact nasal absorption. Various delivery systems including drops, sprays, and gels can be used to administer drugs intranasally. Strategies to enhance nasal absorption include prodrugs, absorption promoters, and cyclodextrins. Nasal delivery has applications for peptides, hormones, and other drugs to improve their bio
New insights on age related association between nasopharyngeal airway clearan...EdwardHAngle
This document summarizes a study that evaluated the relationship between adenoid hypertrophy (enlarged adenoids) and facial morphology in children. The study examined 200 children referred for suspected adenoid obstruction, dividing them into two age groups and four subgroups based on facial divergence. Measurements were made from lateral cephalograms to assess airway clearance and facial morphology. Results found smaller airway measurements and more divergent facial patterns in children aged 6 and under and those with severe facial divergence. The findings suggest earlier airway clearance may be needed in severely affected young children to prevent irreversible facial changes.
Protocol Design and Recruitment StrategyGregg Sweet
1) Recruitment strategy should be developed during protocol design rather than waiting until after protocol completion and site selection. Starting recruitment planning early increases the chances of enrollment success.
2) Marketing support is usually necessary for clinical trials as relying solely on investigators and sites often leads to under-enrollment. Integrated marketing programs are needed to create awareness of trials.
3) Recruitment support should involve a cohesive, organized strategy with consistent messaging across sites and tactics, rather than leaving recruitment planning to individual sites. Specialized recruitment professionals usually have better marketing skills than clinical staff.
VL Presentation: Managing Protocol Deviation using Authorization CodesVeracity Logic, LLC
The document discusses how Veracity Logic's Interactive Response Technology (VLIRT) can be used to manage protocol deviations using authorization codes. It describes setting up authorization codes to be used for subjects outside an age range or for recording activity outside a predefined window. It shows how the system prompts for an authorization code in these situations and generates a report afterward listing the codes used, subjects, and reasons. Contact information is provided for any questions.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise stimulates the production of endorphins in the brain which elevate mood and reduce stress levels.
El documento describe diferentes tipos de mundos literarios, incluyendo mundos cotidianos que representan nuestro mundo realista, mundos míticos que contienen relatos orales de hechos fabulosos del pasado, y mundos oníricos que representan los sueños a través de la narrativa subjetiva. También describe mundos según el efecto perseguido, como mundos realistas que buscan reflejar la realidad de manera objetiva, mundos fantásticos que provocan enigmas sobre la naturaleza del mundo, y mundos utópicos que
El documento define el medio ambiente como todo lo que rodea a un ser vivo, incluyendo seres vivos, objetos, agua, suelo, aire y sus interacciones, así como elementos culturales. Explica que el medio ambiente comprende los valores naturales, sociales y culturales de un lugar y tiempo que influyen en la vida humana y futuras generaciones. Además, describe el origen etimológico de las palabras "medio" y "ambiente" del latín.
Parminder Jhaj is seeking a full-time position in information systems, analytics, or IT operations utilizing their analytical and problem-solving skills. They graduated from the University of Illinois at Chicago with a Bachelor of Science in Information & Decision Sciences and a 3.8 GPA. Relevant experience includes gathering requirements for an SDLC restaurant automation project and creating a website and ATM simulator using programming languages. Additional skills include Microsoft Office, databases, project management, digital marketing, and information security.
This document is a resume for Aricka Marshall providing her contact information, objective, skills, education, and work experience. She has over 10 years of experience in retail, customer service, assembly, and warehouse roles. Her most recent positions include office manager, house keeper, and various temp roles in machining, assembly, and receiving. She aims to utilize her experiences and skills like attention to detail, teamwork, and computer skills to provide quality customer service.
Geotourism Means Accessible & InclusiveScott Rains
The document provides a list of questions for geotourism projects to consider regarding inclusiveness for travelers with disabilities. It asks if information is provided in accessible formats, if websites follow accessibility standards, if activities can be inclusive of all abilities, if marketing portrays people with disabilities respectfully, if employees with disabilities are hired in mainstream roles, and if universal design principles are followed to ensure accessibility for all. The questions also address legal obligations under the UN Convention on Rights of Persons with Disabilities and how sustainable tourism criteria can enhance experiences for travelers, employees and local residents with disabilities.
In the Bible, Colossians 2:8 reads – “Beware lest any man take you captive through vain and deceitful philosophy, after the tradition of men, after the rudiments of the world, and not after Christ.” Since Darwin published his book of Origins 150 years ago, civilization has been on a dangerous journey of replacing God and His creation of the Universe, with what the Bible calls the “vain and deceitful” philosophies of men. These men…and women….. have been teachers, politicians, rock stars, news anchors, even some pastors and preachers. Those philosophies are evolution, naturalism, humanism, Nazism, Marxism, socialism, etc.. These philosophies have led to the social diseases of racism, abortion, eugenics, materialism, and more......
Comunicado Venezuela contra injerencia de Luis AlmagroteleSUR TV
El Gobierno de Venezuela repudió este martes el "ilegítimo e ilícito pretendido informe sobre Venezuela" presentado por el secretario general de la Organización de Estados Americanos (OEA), Luis Almagro, que promueve una intervención extranjera.
This document summarizes a study that investigated sex-based differences in bronchiolar epithelial injury and repair following naphthalene inhalation in rats. The key points are:
1) Male and female rats were exposed to naphthalene vapor and sacrificed at various time points to assess injury and regeneration of bronchiolar epithelium.
2) Naphthalene exposure induced bronchiolar cell exfoliation peaking at 24 hours in both sexes. Male epithelium fully regenerated by 14 days, while females still had some exfoliated cells at 14 days that disappeared by 21 days.
3) Injury occurred earlier and involved more cells in females, while regeneration occurred earlier in males
Nasal drug delivery provides direct access to the systemic circulation while avoiding first-pass metabolism and potential degradation in the gastrointestinal tract. The nasal cavity has a large surface area and highly vascularized nasal mucosa that allows for rapid drug absorption. Various nasal drug formulations have been developed, including sprays, gels, and powders, to enhance drug retention and absorption in the nasal cavity. The nasal route is promising for local and systemic delivery of peptides, proteins, and central nervous system targeting of drugs.
—Fungal organisms are ubiquitous. A common location for these organisms to enter the human body is through the external acoustic canal, oral cavity, and pharynx and sino-nasal cavity. A study was conducted with clinical and mycological analysis of various fungal infections in ENT. Patients suspected for having fungal infections attending at Department of ENT were interrogated and analysed. Swabs collected from these cases were sent for direct microscopy by KOH mounts for fungal examination and fungal culture. Microbiological confirmed 100 cases were finally included in the study Histopathological examination of nasal mass and polyposis was also done. It was observed in this present study otomycosis was most common and accounted for 84% of the total cases followed by candidiasis in oral cavity and pharynx in 9%, allergic fungal rhinosinusitis in 4% and rhinosporidiosis in 3%. Aspergillus niger was that most common fungus isolated in 61% cases, followed by Candida albicans in 24% cases, Aspergillus flavus in 9% cases, Aspergillus fumigatus and Rhinosporodium seeberi in 3% cases each. All the cases of fungal infection of oral cavity and oropharynx were due to Candida albicans.
1) The growth pattern and role of the tonsils and adenoids in dentofacial development are controversial topics that have been debated for many years. While enlarged tonsils and adenoids can affect breathing and dentofacial structure, the criteria for determining when surgical removal is needed are not well-defined.
2) Tonsils and adenoids play an important role in the immune system as the primary sites of exposure to antigens. However, it is unclear whether surgical removal compromises immune function. Some studies have found lower antibody levels or increased cancer risk after removal, while others have not.
3) There is ongoing debate around the benefits of tonsillectomy and adenoidectomy
This document summarizes an article by Allen J. Moses about obstructive breathing conditions and their implications for dental treatment. It describes an appliance called a "passivator" that supports the mandible in an open bite position without causing tooth movement. The document discusses how nasal obstruction can cause mouth breathing, which can lead to issues like narrow arches and abnormal swallowing. It reviews studies on monkeys that found oral breathing altered neuromuscular activity and bone structure. The most common causes of nasal obstruction in humans are also outlined.
This document provides an update to the 2006 clinical practice guideline for managing acute otitis externa (AOE). The update was needed due to new clinical trials, systematic reviews, and lack of consumer participation in the original guideline development. AOE is defined as diffuse inflammation of the external ear canal and remains a common infection. Topical antimicrobial therapy is effective for AOE but oral antibiotics are often inappropriately prescribed. The guideline makes recommendations for the diagnosis, treatment, and management of AOE with a focus on appropriate use of analgesics and topical vs. oral antimicrobials.
This document summarizes a study that analyzed the bacterial profiles of saliva samples from 292 participants with low levels of oral diseases. The study found:
1) The predominant bacteria in saliva were Streptococcus and Veillonella.
2) Differences in diet, lifestyle factors (age, gender, BMI, alcohol consumption), and diet composition did not influence bacterial profiles.
3) Smokers had higher levels of Streptococcus sobrinus and Eubacterium brachy compared to non-smokers.
4) Socioeconomic status may influence bacterial profiles, as profiles differed between high and low socioeconomic groups.
This document reviews nasal polyposis (NP), a common condition affecting up to 4% of the population. It discusses the unclear etiology of NP, associated with factors like allergy, asthma, and infection. Clinical features include nasal obstruction, anosmia, and polypoid masses visible during examination. Management involves medical therapy like corticosteroids as primary treatment and to prevent recurrence, as well as surgery for refractory cases. Recurrence is common even after treatment.
Nasal drug delivery is an alternative to oral administration that avoids first-pass metabolism and allows for rapid systemic absorption. The nasal cavity has features making it suitable for drug delivery such as a large surface area, porous epithelium, and avoidance of first-pass metabolism. Drugs are transported across the nasal epithelium through passive diffusion or active transport. Factors like particle size, molecular weight, pH, and concentration impact nasal absorption. Various delivery systems including drops, sprays, and gels can be used to administer drugs intranasally. Strategies to enhance nasal absorption include prodrugs, absorption promoters, and cyclodextrins. Nasal delivery has applications for peptides, hormones, and other drugs to improve their bio
New insights on age related association between nasopharyngeal airway clearan...EdwardHAngle
This document summarizes a study that evaluated the relationship between adenoid hypertrophy (enlarged adenoids) and facial morphology in children. The study examined 200 children referred for suspected adenoid obstruction, dividing them into two age groups and four subgroups based on facial divergence. Measurements were made from lateral cephalograms to assess airway clearance and facial morphology. Results found smaller airway measurements and more divergent facial patterns in children aged 6 and under and those with severe facial divergence. The findings suggest earlier airway clearance may be needed in severely affected young children to prevent irreversible facial changes.
Vocal fold polyps are one of the most common benign laryngeal lesions. They are generally caused by phonotrauma but can also be associated with smoking, gastroesophageal reflux, or respiratory activities. Histologically, polyps show swelling in the lamina propria and an increase in blood vessels. While some studies find no difference between polyp and nodule histology, others demonstrate morphological changes in polyp tissue. Surgery is often used to treat polyps but recent research shows speech therapy can also be effective as primary treatment, with total or partial regression of lesions in some cases. The literature review found discrepancies but also notable progress in otolaryngologic techniques and effectiveness of speech therapy as initial treatment
La sindrome rino bronchiale. indagine conoscitiva sio-aimar.Merqurio
This document describes a survey conducted by the Italian Society of Otorhinolaryngology and the Interdisciplinary Scientific Association for the Study of Respiratory Diseases to better understand the epidemiology, diagnosis, and treatment of rhino-bronchial syndrome. 159 patients from 9 ENT and pulmonology centers were enrolled based on clinical history and symptoms. 116 patients received a confirmed diagnosis based on examinations of the upper and lower airways. Allergic and infectious diseases were more common in patients with a confirmed diagnosis. After 3 months of standard treatment, 96% of patients recovered. The study proposes a diagnostic workflow and emphasizes the importance of correct diagnosis through multidisciplinary evaluation and treatment.
La sindrome rino bronchiale. indagine conoscitiva sio-aimar.Merqurio
This study aimed to standardize the diagnosis and treatment of rhino-bronchial syndrome (RBS), which links inflammation of the upper and lower airways. 159 patients meeting criteria for RBS underwent a two-level diagnostic protocol including endoscopy and spirometry. RBS was confirmed in 116 patients who had higher rates of allergic and infectious diseases than unconfirmed cases. Common symptoms were nasal obstruction, rhinorrhea, cough, and dyspnea. After 3 months of treatment including steroids, antibiotics, and nasal lavage, 96% of patients recovered. The study proposes a diagnostic workflow and highlights the importance of correct diagnosis through multidisciplinary evaluation for effective treatment of RBS.
This document discusses the relationship between periodontal and respiratory diseases. It begins by describing the human respiratory system and its defense mechanisms. Key respiratory diseases like bacterial pneumonia and chronic obstructive pulmonary disease are explained. Evidence is presented that shows oral bacteria can cause respiratory infections by aspirating into the lungs or modifying surfaces to promote pathogen adhesion. Maintaining oral health through practices like toothbrushing and chlorhexidine use may help prevent respiratory infections by reducing oral bacterial loads and pathogen reservoirs. The document concludes by stating periodontal therapy may help improve lung function in COPD patients with chronic periodontitis.
1. Disorders of olfaction can be conductive, resulting from nasal obstruction, or sensorineural, due to damage to the olfactory neuroepithelium.
2. Common causes of sensorineural disorders include upper respiratory infections, head trauma, tumors near the olfactory region, congenital defects, toxins, age-related changes, and neurodegenerative diseases.
3. Specific conditions that can cause olfactory disorders are post-viral olfactory dysfunction, Kallmann syndrome, septo-optic dysplasia, holoprosencephaly, exposure to metals or other toxins, Alzheimer's disease, Parkinson's disease, and epilepsy presenting with olfactory auras.
Allergen Skin Test Reactivity and Eosinophilia in Adult Bronchial Asthmatic P...MatiaAhmed
1) The document summarizes a study on allergen skin test reactivity and eosinophilia in adult bronchial asthmatic patients.
2) The study found that the maximum number of asthmatic patients had positive skin prick tests for dust mites. Dust mites were found to be a significant allergen followed by house dust and cockroach.
3) The mean eosinophil count was significantly higher in asthmatic adults compared to healthy subjects. However, the association between positive skin prick tests and increased eosinophil counts was not statistically significant.
4) In conclusion, the study found that dust mites, house dust, and cockroaches are common allerg
Epidemiology is the study of disease distribution and factors influencing distribution in human populations. It aims to prevent disease and maintain health. There are three main components: population, distribution, and factors. Epidemiology uses descriptive and analytical study designs like cohort studies and case-control studies to investigate relationships between exposures and health outcomes. Key measures include DMFT index for dental caries and Community Periodontal Index for periodontal disease.
Bacteriological and Mycological Profile of Chronic Suppurative Otitis Media I...inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Kaiser. ffns a single treatment for sar. jaci 07Christian Wijaya
This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis symptoms. Over 2 weeks, 299 patients received either fluticasone furoate 110 mcg or placebo once daily. Fluticasone furoate produced significantly greater improvements than placebo in reflective total nasal symptom scores, morning instantaneous total nasal symptom scores, reflective total ocular symptom scores, and patient-rated overall response to therapy. Treatment with fluticasone furoate also resulted in improvements in health-related quality of life. Fluticasone furoate was well tolerated with no serious adverse events
Similar to The Route of Exposure Influences Nasal Lesion Distribution in Rats in NTP Studies (20)
Thymomas in Fischer 344N Rats in The National Toxicology Program DatabaseEPL, Inc.
Thymomas are rare tumors in F344/N rats. This study summarizes 277 thymomas from NTP studies. Most thymomas were benign (84.8%) and showed heterogeneous morphology but were categorized into 6 patterns. Malignant thymomas comprised 15.2% and were diagnosed based on invasion, metastasis, or cytology. Malignant thymomas were associated with shorter survival times. While morphology varied, there was no correlation with behavior. Classification into benign vs malignant adequately describes thymomas in F344/N rats.
Right Ventricular Cardiomyopathy in the Rat - Is There an Association with Ga...EPL, Inc.
This study evaluated whether right ventricular cardiomyopathy in rats was associated with gavage administration. The incidence and severity of cardiomyopathy was compared between gavage and non-gavage rats. The results showed similar rates of cardiomyopathy between gavage and non-gavage rats of both strains studied. Histopathological examination also showed the lesions were identical regardless of administration method. Therefore, the study concluded right ventricular cardiomyopathy in rats is unrelated to the gavage technique of exposure.
Dietary Administration of Diquat for 13 Weeks Does Not Result in a Loss of Do...EPL, Inc.
Dietary Administration of Diquat for 13 Weeks Does Not Result in a Loss of Dopaminergic Neurons in the Substantia Nigra Pars Compacta (SNpc) of C57BL/6J Mice
Renal Tubular Pigmentation Associated with Senna-Related MetabolitesEPL, Inc.
“Renal Tubular Pigmentation Associated with Senna-Related Metabolites.” Willson GA (presenter) Malarkey DE, Allison N, Harris N, Miller RA. The 54th Annual Society of Toxicology Meeting. San Diego, CA. March 25, 2015.
For full-resolution viewing, please open or save as a PDF.
Acquiring Practical Population Estimates of Neurons Through Design-Based Ster...EPL, Inc.
“Acquiring Practical Population Estimates of Neurons Through Design-Based Stereology: Dissecting the Disector.” Zadory D, Burton E, Wolf JC. The 44th Annual Meeting of the Society for Neuroscience. Washington, DC. November 19, 2014.
For full-resolution viewing, please open or save as a PDF.
The National Toxicology Program Nonneoplastic Lesion AtlasEPL, Inc.
The National Toxicology Program (NTP)’s Nonneoplastic Lesion Atlas is a valuable, web-based resource with thousands of high-quality, enlargeable images, diagnostic
guidelines, and preferred NTP terminology for numerous nonneoplastic rodent lesions. The atlas will be used by the NTP and its many pathology partners to standardize lesion diagnosis, terminology, and the way lesions are recorded in NTP studies. The goal is to improve the consistency and accuracy of the diagnosis of nonneoplastic lesions between pathologists and laboratories to improve the organization and utility of the NTP’s nonneoplastic lesion database and, ultimately, our understanding of nonneoplastic lesions. The NTP Nonneoplastic Lesion Atlas is a living document that complements the INHAND publications. In fact, one of the aims of the atlas is to align the NTP terminology with that of the INHAND publications as much as possible. The atlas is also a useful training tool for pathology residents and can be used by any organization to improve their own nonneoplastic lesion database. A total of 56 organs organized into 13 organ systems will be included in the completed project. The atlas is free to the public at http://ntp.niehs.nih.gov/nnl.
Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbesto...EPL, Inc.
“Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure.” Willson GA (presenter), Dodd DA, Roberts KC, Wall HG, Jarabek AM, Gavett SH. The 33rd Society of Toxicologic Pathology Annual Meeting. Washington, DC. June 22-26, 2014.
“Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure.” Dodd DA (presenter), Willson GA, Roberts KC, Wall HG, Jarabek AM, Gavett SH. The 53rd Annual Society of Toxicology Meeting. Phoenix, AZ. March 23-27, 2014.
For full-resolution viewing, please open or save as a PDF.
Immunohistochemical Characterization of ENU-induced Brain Tumors in F344 RatsEPL, Inc.
“Immunohistochemical Characterization of ENU-induced Brain Tumors in F344 Rats.” Moore RR (presenter), Kolenda-Roberts H, Harris NA, Cho YM, Ogawa K, Hardisty JF, Miller RA. The 33rd Society of Toxicologic Pathology Annual Meeting. Washington, DC. June 22-26, 2014.
For full-resolution viewing, please open or save file as a PDF.
Non-lesions, Misdiagnoses, Missed Diagnoses, and Other Interpretive Challenge...EPL, Inc.
“Non-lesions, Misdiagnoses, Missed Diagnoses, and Other Interpretive Challenges in Fish Histopathology Studies: A Guide for Investigators, Authors, Reviewers, and Readers.” Wolf JC (presenter), Baumgartner WA, Blazer VS, Camus AC, Engelhardt JA, Fournie JW, Frasca S, Groman DB, Kent ML, Khoo LH, Law JM, Lombardini ED, Ruehl-Fehlert C, Segner HE, Smith SA, Spitsbergen JM, Weber K, Wolfe MJ. The 33rd Society of Toxicologic Pathology Annual Meeting. Washington, DC. June 22-26, 2014.
For full-resolution viewing, please open or save file as a PDF.
EPL, Inc. - Comparative Anatomy of the EyeEPL, Inc.
Proper evaluation of potential effects of test articles on the eye and its components requires attention to detail in the preparation and examination of specimens. EPL has developed critical capability in histology to produce consistent microscopic sections that facilitate the pathologist’s evaluation of the various segments of the eye. The EPL methodology is applicable to all routes of administration, including intravitreal, topical, or systemic. The veterinary pathologists at EPL have many years of experience evaluating effects on the eye; EPL is the premier source for ocular pathology evaluation. In addition to standard histology and histopathology, special preparations may be included (e.g., special histochemical stains, immunohistochemistry) to further characterize lesions.
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central19various
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The Route of Exposure Influences Nasal Lesion Distribution in Rats in NTP Studies
1. The Route of Exposure Influences Nasal Lesion Distribution in Rats in NTP Studies
Karen Y. Cimon1, Rebecca R. Moore2, Rodney A. Miller1, Gabrielle A. Willson1, Arun R. Pandiri3, and David E. Malarkey3
1Experimental Pathology Laboratories, Inc., Research Triangle Park, NC, USA, 2 Integrated Laboratory Systems, Research Triangle Park, NC, USA,
3Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
Introduction: Nasal toxicity is not only observed in inhalation exposure
studies but also in drinking water and gavage studies. Nasal toxicants may
act systemically, directly, or both and the occurrence and distribution may
provide clues to the pathogenesis. This review focuses on nasal lesion
occurrence, features, and distribution as seen in a chronic whole body
inhalation study compared to two drinking water and three gavage studies
with nasal toxicity conducted by the NTP.
Methods: We examined all 3 routine sections of nose from all control and
high dose male and female F344N rats. The general distribution of nasal
and nasopharyngeal duct lesions was recorded and mapped as
predominately anterior or posterior; dorsal or ventral; and unilateral or
bilateral.
Results: Nasal lesions in the inhalation study were of varying severity,
occurred predominately as bilateral and dorsal; more frequently in the
anterior sections (98%) of the nose and less often (18%) in the most
posterior section of the nasal cavity. In the 2 drinking water studies, the
nasal lesions were uniformly observed in the middle and posterior nasal
sections; only olfactory epithelium was affected; and lesions had a dorsal
and bilateral distribution in 90% or 100% of the rats. In the 3 gavage
studies, the nasal lesions varied in character and distribution; tended to be
more posterior and ventral, and were predominately unilateral. Lesions in
the nasopharyngeal duct occurred irregularly and only in the gavage
studies. The changes in the gavage studies were similar in male and
female rats.
Impact Statement: Most inhalation or systemically induced nasal effects
are uniform in tissue specificity and/or distribution, thus affecting tissues in
anatomically consistent manner. The nasal lesions in the 3 gavage studies
resembled those described as related to gavage-related reflux. When
patterns of distribution of nasal lesions are not uniform or not consistent
with known patterns of induced lesions, then one must consider an
alternative pathogenesis, e.g., gastric reflux, gavage accidents or
aspiration.6,7,8
Abstract
Figure 3
Inhaled toxicants often induce nasal lesions in a site-specific manner.
Irritants like formaldehyde often cause lesions largely restricted to the
anterior nose where it symmetrically affects the respiratory and transitional
epithelia and the effect progressively lessens posteriorly. In contrast,
inhaled methyl bromide affects olfactory epithelium preferentially, leaving
the more anterior epithelia unaffected.1 Mapping lesions can effectively
demonstrate the unique distribution of nasal lesions.2,3 Lesion distribution
can be a function of airflow patterns delivering a local tissue dose or a
unique tissue susceptibility related to local metabolism. Compounds
administered parenterally can result in nasal lesions via systemic delivery
of toxic metabolites to susceptible nasal tissues or from systemic delivery
and subsequent local metabolism of the compound by the nasal, often,
olfactory epithelium.4 Most observed nasal effects are uniform, affecting
tissues in anatomically consistent and locally specific manners. When
patterns of distribution of nasal lesions are not uniform or not consistent
with known patterns of induced lesions, then one must consider an
alternative pathogenesis, e.g., gastric reflux, gavage accidents or
aspiration.6,7,8 The working hypothesis for this review was that there can
be a difference in nasal lesion distribution and quality, that may vary with
the route of exposure. The objective of this review was to revisit studies
having various routes of exposure and to record and evaluate nasal lesion
patterns to see if differences could be seen.
Introduction
Figure 2
1. The Nose Revisited: A Brief Review of the Comparative Structure, Function, and Toxicologic
Pathology of the Nasal Epithelium. Harkema et al. Toxicol Pathol. 2006:34(3):252-69.
2. Nasal Dosimetry, Lesion Distribution, and the Toxicologic Pathologist: A Brief Review. Morgan,
K. T. Inhalation Toxicol. 1994:6:41-57.
3. Histopathology of Nasal Olfactory Mucosa from Selected Inhalation Toxicity Studies Conducted
with Volatile Chemicals. Hardisty et al. Toxicol Pathol. 1999:27(6):618-627.
4. Respiratory Tract Lesions in Noninhalation Studies. Sells et al. Toxicol Pathol. 2007:35(1):170-
77.
5. Unexpected Nasal Changes in Rats Related to Reflux after Gavage Dosing. Damsch et al.
Toxicol Pathol. 2011:39(2):337-47.
6. Gavage-Related Reflux in Rats: Identification, Pathogenesis, and Toxicologic Implications
(Review). Damsch et al. Toxicol Pathol. 2011:39(2):348-60.
7. Impact of Gavage Dosing Procedure and Gastric Content on Adverse Respiratory
Effects and Mortality in Rat Toxicity Studies. Eichenbaum et al. J Appl Toxicol. 2011:31(4):342-
64.
8. National Toxicology Program Technical Report Series, 1990 March;377:1-211.
9. NTP TOX 40. Toxicity Studies of β-Bromo-β-Nitrostyrene (CAS No. 7166-19-0) Administered
by Gavage to F344/N Rats and B6C3F1 Mice.
10. NTP TR-399. Toxicology and Carcinogenesis Studies of Titanocene Dichloride (CAS No. 1271-
19-8) in F344/N Rats (Gavage Studies).
11. Drug Metabolism in the Nasal Cavity: Relevance to Toxicology. Reed, C. J. Drug Metab Rev.
1993:25(1-2):173-205.
References
To elucidate the importance of lesion distribution, we examined all
histologic sections of nose from all control and high dose rats from six
NTP studies; 1 inhalation, 2 drinking water, and 3 gavage studies. The
incidences of final diagnoses can be found in the NTP technical reports for
each study. Terms have been devised to reflect the expressions of
distribution and general pathological processes.
The studies reviewed included a chronic inhalation study, o-
chlorobenzalmalononitrile (CS2), methyl ethyl ketoxime and dipropylene
glycol (two subchronic drinking water studies), β-bromo-β-nitrostyrene (a
4-week gavage study), titanocene dichloride (a chronic gavage study), and
the green tea extract (a chronic gavage study).
The standard three NTP nose sections were evaluated in all control and
high dose rats except for titanocene, an older study where only anterior
and middle nose sections were present (the typical third nose section with
the ethmoid turbinates and nasopharyngeal duct was not present).
Treatment-related lesions noted in the noses were designated as
unilateral, bilateral, anterior, posterior, dorsal, or ventral. The site-specific
distribution of nose and nasopharyngeal duct lesions was depicted on
diagrams of transverse sections of the three nose levels, and on a
diagrammatic depiction of a longitudinal nose section.
Methods
Figure 1
This review highlights the importance of recognizing nasal lesion
distribution patterns. Nasal toxicants tend to express themselves in
somewhat unique and consistent patterns of distribution.1 Variance
from expected patterns, irregular lesion incidences across groups, or
lesions in unanticipated locations should alert us to consider
alternate pathogeneses or different interpretations.
Inhalation exposure of formaldehyde and other nasal irritants induce
lesions with an anterior to posterior nasal gradient affecting
transitional and respiratory epithelium preferentially, while inhaled
methyl bromide affects only olfactory epithelium, both toxicant
effects being expressed bilaterally.1
Occasionally, lesions observed in the nose can be the result of
gastric reflux or regurgitation. In this instance, the nasal lesions tend
to be less uniform in terms of distribution and symmetry. Lesions in
the nose related to reflux tended to be more unilateral, more ventral
and more posterior. Acute lesions of epithelial necrosis overlying a
chronically altered epithelium and suppurative lesions in the
nasopharyngeal duct may also signal reflux as a possible cause.5,6,7
Chemicals administered parenterally can affect the respiratory
epithelium but more often they affect the olfactory epithelium.4
Significant metabolic activity has been observed in the nasal
epithelium and may explain some regional susceptibility. The
distribution of the metabolic enzymatic activity tends to be bilateral
and in the case of the olfactory epithelium, in the posterior nose
sections.11
Lesion distribution can be attributed to delivered local dose and or
specific tissue susceptibility.2 Local dose can be affected by airflow,
mucous flow, systemic delivery via vascular perfusion,
physicochemical properties of the agent, and metabolism.1
Discussion
Grateful thanks for assistance with this poster to Emily Singletary and
David Sabio of EPL; and to Lois Wyrick of Image Associates.
Acknowledgements
Male and female rats had similar lesions and lesion distribution related to
the various routes of exposure; therefore, for space conservation, only
data from the high dose female rats was used for illustrative purposes.
*There was no third nasal section in this study
*There was no third nasal section in this study
Inhalation of CS2, a tear gas, elicited an irritant response in the nose in a
dose-related manner. The rats had bilateral hyperplasia and squamous
metaplasia of the respiratory epithelium and chronic focal inflammation in
primarily the first nasal section; and a lesser incidence of bilateral olfactory
epithelial degeneration and metaplasia in the second and third nasal
sections, effectively establishing a lessening of lesions with an anterior to
posterior gradient.8
Methyl ethyl ketoxime (drinking water) caused degeneration only of the
olfactory epithelium lining the bilateral dorsal meatuses of the second and
third nose sections in the two highest exposure groups and no lesions in
control or lower exposure groups.
Dipropylene glycol (drinking water) also caused degeneration of the
olfactory epithelium bilaterally in the dorsal meatus of the second and third
nasal sections. The highest exposure group only was affected, with no
lesions observed in the control or lower exposure groups.
β-bromo-β-nitrostyrene (gavage) was associated with a low incidence of
nasal lesions, including inflammation and olfactory epithelial degeneration,
plus suppurative lesions in the nasopharyngeal duct in two females. The
lesions were mainly posterior and ventral. Review of the technical report
showed that the incidence of nasal lesions varied widely among the
control and five treated groups with some of the lower dose groups having
more lesions than the high dose group. The technical report attributed the
nasal lesions to gastric reflux and aspiration.9
Titanocene dichloride (gavage) was associated with a prominent increase
in necrosis, degeneration and inflammation of the nasal mucosa.
Occasional mycotic infections occurred. These nose lesions were
somewhat evenly distributed anterior to posterior, but clearly had a ventral
and unilateral predisposition. The technical report attributed the nasal
lesions to gastric reflux and aspiration.10
Green tea extract (gavage) was associated with a prominent nasal lesion
complex including, but not limited to, degeneration of olfactory epithelium,
necrosis, suppuration, chronic inflammation, and epithelial hyperplasia
and squamous metaplasia of respiratory and olfactory epithelium. Foreign
bodies, (hair, plant), were observed. These lesions were present in a
predominately, but not exclusively, ventral, posterior and unilateral
manner. Acute lesions of epithelial necrosis overlaid chronic areas of
inflammation at times. The nasopharyngeal duct frequently experienced
necrosis, suppurative inflammation, chronic inflammation and epithelial
hyperplasia.
Figures 1-4 are typical lesions that were associated with exposure to
these chemicals. Figures 5-10 depict the relative lesion distribution
associated with these 6 exposures.
Results
Chemical Study type
Rats with
lesions - Nose
level 1
Rats with
lesions - Nose
level 2
Rats with lesions -
Nose level 3
Rats with lesions -
Nasopharyngeal duct
CS2 Chronic inhalation 49/50 25/50 9/50 0/50
Methyl ethyl
ketoxime
90-Day
Subchronic In
water
0/10 10/10 10/10 0/10
Dipropylene
glycol
90-Day
Subchronic In
water
0/10 10/10 9/10 0/10
β-bromo-β-
nitrostyrene
28-Day
Gavage
0/10 1/10 1/10 2/10
Titanocene
dichloride*
Chronic
Gavage
7/50 9/50 NA* NA*
Green tea extract
Chronic
Gavage
19/60 42/50 40/60 34/50
Chemical Study type
Lesions
mainly
anterior
Lesions
mainly
posterior
Lesions
mainly
dorsal
Lesions
mainly
ventral
Lesions
mainly
unilateral
Lesions mainly
bilateral
CS2
Chronic
inhalation
+ - + - - +
Methyl ethyl
ketoxime
90-Day
Subchronic
in water
- + + - -
+
Dipropylene glycol
90-Day
Subchronic
In water
- + + - - +
β-bromo-β-
nitrostyrene
28-Day
Gavage
- + - + - +
Titanocene
dichloride*
Chronic
Gavage
-
- - + + -
Green tea extract
Chronic
Gavage
- + - + + -
Figure 4
Lesions suggestive of gastric reflux are present in of the
third nasal section from a male Wistar Han rat. There is
suppurative inflammation in the ventral nasal cavity and
nasopharyngeal duct. Chronic exposure to green tea
extract by gavage. (H&E)
Irritant response in the nasal turbinates in the first nasal
section from a male F344/N rat exposed via inhalation to
CS2 (chronic study). Shown are hyperplasia and
squamous metaplasia of the respiratory epithelium.
(H&E)
Bilateral degeneration of the olfactory epithelium in the
dorsal meatuses in the second nose section from a
female F344/N rat exposed to dipropylene glycol via
drinking water (subchronic study). (H&E)
Lesions similar to those seen with gastric reflux are
present in the dorsal lateral portion of the third nasal
section in a male Wistar Han rat. There is unilateral
suppurative inflammation associated with chronic
exposure to green tea extract by gavage. (H&E)
Figure 5 Figure 6
Figure 7 Figure 8
Figure 9 Figure 10
Relative Lesion Distribution (Red)
CS2, Chronic Inhalation, Female Rats
Relative Lesion Distribution (Red)
Methyl Ethyl Ketoxime, Subchronic in Water, Female Rats
Relative Lesion Distribution (Red)
Dipropylene Glycol, Subchronic in Water, Female Rats
Relative Lesion Distribution (Red)
β-Bromo-β-Nitrostyrene, 4 Week Gavage, Female Rats
Relative Lesion Distribution (Red)
Titanocene dichloride, Chronic Gavage, Female Rats
Relative Lesion Distribution (Red)
Green Tea Extract, Chronic Gavage, Female Rats