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Toxicology and Applied Pharmacology Aug 2016Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment... (Review)
Review
Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.
Topics: Animals; Chemical Warfare Agents; Fibrin; Humans; Irritants; Lung; Lung Injury; Matrix Metalloproteinases; Mesenchymal Stem Cells; Mustard Gas; RNA, Untranslated; Reactive Nitrogen Species; Reactive Oxygen Species; Transforming Growth Factor beta; Transient Receptor Potential Channels; Tumor Necrosis Factor-alpha
PubMed: 27212445
DOI: 10.1016/j.taap.2016.05.014 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jul 2022Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At...
OBJECTIVES
Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects.
METHODS
A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (=22) or FJ (=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method.
RESULTS
In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (=0.066).
CONCLUSIONS
There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.
Topics: Constriction, Pathologic; Esophageal Neoplasms; Fistula; Free Tissue Flaps; Humans; Hypopharynx; Jejunum; Necrosis; Postoperative Complications; Plastic Surgery Procedures; Retrospective Studies; Thigh
PubMed: 36039585
DOI: 10.11817/j.issn.1672-7347.2022.210763 -
Internal Medicine (Tokyo, Japan) Dec 1997Aspiration pneumonia is associated with decreases in both swallowing and cough reflexes and is the most common cause of death in the elderly. Basal ganglia strokes might... (Review)
Review
Aspiration pneumonia is associated with decreases in both swallowing and cough reflexes and is the most common cause of death in the elderly. Basal ganglia strokes might predispose these patients to develop pneumonia owing to reductions of both reflexes, resulting in frequent aspiration during sleep. An impairment of dopamine metabolism in the basal ganglia is observed in these patients and levodopa administration improves the impaired swallowing reflex. Both swallowing and cough reflexes are mediated by endogenous substance P (SP) released from vagal sensory nerves in the pharynx and upper airways. The addition of a low dose of capsaicin to liquid or food, which stimulates the release of SP, may help prevent aspiration pneumonia. Angiotensin-converting enzyme inhibitor decreases SP catabolism resulting in improvements in both reflexes. Oral care and the sitting position after meals may decrease aspiration pneumonia in the elderly.
Topics: Aged; Aging; Basal Ganglia; Cerebral Infarction; Cough; Deglutition; Humans; Pneumonia, Aspiration
PubMed: 9475237
DOI: 10.2169/internalmedicine.36.851 -
Progress in Neuro-psychopharmacology &... Dec 2013With roughly 234 million people undergoing surgery with anesthesia each year worldwide, it is important to determine whether commonly used anesthetics can induce any... (Review)
Review
With roughly 234 million people undergoing surgery with anesthesia each year worldwide, it is important to determine whether commonly used anesthetics can induce any neurotoxicity. Alzheimer's disease (AD) is the most common form of age-related dementia, and a rapidly growing health problem. Several studies suggest that anesthesia could be associated with the development of AD. Moreover, studies in cultured cells and animals show that commonly used inhalation anesthetics may induce changes consistent with AD neuropathogenesis, e.g., β-amyloid protein accumulation. Therefore, in this mini review, we focus on the recent research investigating the effects of commonly used anesthetics including isoflurane, sevoflurane, desflurane, nitrous oxide, and propofol, on Aβ accumulation in vitro and in vivo. We further discuss the future direction of the research determining the effects of anesthetics on β-amyloid protein accumulation.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Anesthetics, General; Humans
PubMed: 22918033
DOI: 10.1016/j.pnpbp.2012.08.002 -
Dysphagia Oct 2022Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia. In adults, this stroke is the...
Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia. In adults, this stroke is the most common brainstem stroke, but it is rare in the pediatric population. Insults to the medulla can involve the "swallowing centers," the nucleus ambiguus and nucleus tractus solitarius, and the cranial nerves involved in swallowing, namely IX (glossopharyngeal) and X (vagus). These individuals can develop severe dysphagia with an inability to trigger a swallow due to pharyngeal weakness and impaired mechanical opening of the upper esophageal sphincter (UES) which can result in aspiration. We present a 7-year-old male with 22q11.2 deletion syndrome (velocardiofacial syndrome) and velopharyngeal insufficiency who underwent pharyngeal flap surgery at an outside hospital whose post-operative course was complicated by adenovirus, viral myocarditis, and dorsal medullary stroke. He required a tracheostomy and gastrostomy tube. He was discharged from that hospital and readmitted to our hospital 4 months later for increased oxygen requirement, requiring a 5 month admission in the intensive care units. His initial VFSS revealed absent UES opening with the entire bolus remaining in the pyriform sinuses resulting in aspiration. His workup over the course of his admission included multiple videofluoroscopic swallow studies (VFSS), flexible endoscopic evaluation of swallowing (FEES), and pharyngeal and esophageal manometry. Intervention included intensive speech therapy, cricopharyngeal Botox® injection, and cricopharyngeal myotomy. Nineteen months after his stroke, he transitioned to oral intake of solids and liquids with adequate movement of the bolus through the pharynx and UES and no aspiration on his VFSS.
Topics: Adult; Brain Stem Infarctions; Child; Deglutition; Deglutition Disorders; Esophageal Sphincter, Upper; Humans; Lateral Medullary Syndrome; Male; Manometry; Stroke
PubMed: 34705083
DOI: 10.1007/s00455-021-10376-3 -
Emerging Microbes & Infections Dec 2023Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell...
Correlations of Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in the nasopharyngeal specimens with the diagnosis and severity of SARS-CoV-2 infections.
Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.
Topics: Humans; COVID-19; Interleukin-6; Tumor Necrosis Factor-alpha; Retrospective Studies; Adenosine Deaminase; Case-Control Studies; Peroxidase; Ligands; SARS-CoV-2; Cytokines; Chemokines; Nasopharynx; Chemokine CCL22
PubMed: 36482706
DOI: 10.1080/22221751.2022.2157338 -
Ear, Nose, & Throat Journal Jan 2020The laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma continues to be a challenge for surgeons. In this article, we describe our experience with...
The laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma continues to be a challenge for surgeons. In this article, we describe our experience with laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma using the modified infrahyoid myocutaneous flap (IHMCF). The modified incision design for the modified IHMCF and clinical outcomes are also detailed here. Between January 2012 and February 2018, 10 patients with hypopharyngeal squamous cell carcinoma who underwent laryngopharyngeal reconstruction using the modified IHMCF after hemicricolaryngopharyngectomy were included in this study. The drainage vessels of the modified IHMCF, oncological outcomes, and functional reservation of the larynx were recorded. All of the flaps survived well. No flap necrosis or other major complications occurred during follow-up. None of the patients remained on nasogastric feeding for more than 4 weeks postoperatively. The follow-up period ranged from 12 to 73 months (mean, 36 months). In our series, 6 patients were successfully decannulated and 5 had received radiation therapy. We roughly assessed the speech and swallowing functions, and the outcomes seemed acceptable in all of the patients after surgery. Laryngoscopic examination showed that the modified IHMCF survived well and the new glottis provided excellent function and good ventilation results. In our experience, the modified IHMCF is a safe and viable procedure that can serve as a valid alternative to free flaps and the pectoralis major myocutaneous flap to reconstruct laryngopharyngeal defects.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Hyoid Bone; Hypopharyngeal Neoplasms; Hypopharynx; Laryngoplasty; Larynx; Male; Middle Aged; Myocutaneous Flap; Plastic Surgery Procedures; Treatment Outcome
PubMed: 31079475
DOI: 10.1177/0145561319849947 -
Chirurgia (Bucharest, Romania : 1990) 2018Neoplastic invasion of the structures of the cervical region originating from a malignant tumour developed in one of the viscera of the throat may benefit from cervical...
UNLABELLED
Neoplastic invasion of the structures of the cervical region originating from a malignant tumour developed in one of the viscera of the throat may benefit from cervical exenteration. Defined as resection of the hypopharynx, cervical oesophagus, larynx and cervical trachea, exenteration has limited indications and is mandatorily accompanied by digestive tube reconstruction. The aim of this article is to highlight the indication, surgical strategy and important surgical stages illustrated by images from personal professional experience.
MATERIALS AND METHOD
Pharyngo-laryngo-oesophageal en bloc resection and radical cervical lymphadenectomy were followed by reconstruction via free jejunal transfer or colic pedicle grafting. Between 2000 and 2018 we have performed cervical exenteration in 25 patients with tumours originating in the pharynx, larynx or cervical oesophagus. In the cases of 5 patients in whom we did not obtain the oncological safety margin for oesophageal cancer we performed transhiatal pharyngo-laryngo-oesophagectomy. In these patients, we performed reconstruction of the oesophagus with colonic graft. In 20 cases we performed jejunal autotransplant. We recorded 4 perioperative deaths, due to major arterial vessel haemorrhage (1 case), after jejunal necrosis (2 cases), and mediastinitis after oesophageal striping and colonic graft necrosis (1 case). One patient presented tumour recurrence at the level of the tracheal stump. Survival rate varied between 6 months and 4 years for the group of patients who presented for postoperative follow-ups. Cervical exenteration remains an option for tumour recurrence after radiochemotherapy or for obstructive airway or digestive tract tumours. It can be burdened by complications difficult to treat. The surgical team has to adapt its initial surgical strategy to the reality of the surgical field, both in terms of exeresis and in terms of types of pharyngo-oesophageal reconstruction.
Topics: Carcinoma, Squamous Cell; Colon; Esophageal Neoplasms; Esophagectomy; Esophagoplasty; Humans; Hypopharynx; Jejunum; Laryngectomy; Lymph Node Excision; Neck Dissection; Plastic Surgery Procedures; Retrospective Studies; Romania; Survival Rate; Treatment Outcome; Universities
PubMed: 29509539
DOI: 10.21614/chirurgia.113.1.123 -
Journal of Medical Virology Jan 2020This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and... (Comparative Study)
Comparative Study
This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α were detected by multiplex enzyme-linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (P = .001) and HRV + non-RSV (P = .002) groups, and fever in the HRV (P = .004) and HRV + RSV (P = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (P = .010) and HRV + non-RSV (P = .014), and less numerous in summer compared with HRV + non-RSV (P = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (P < .001) and pneumonia (P = .033) cases. HRV bronchiolitis cases had increased IL-4/IFN-γ and decreased TNF-α/IL-10 ratios, compared with HRV pneumonia counterparts. HRV is a major non-RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence, and seasonal prevalence.
Topics: Adolescent; Bronchiolitis; Child; Child, Preschool; Cytokines; Eczema; Female; Fever; Hospitalization; Humans; Infant; Infant, Newborn; Male; Nasopharynx; Picornaviridae Infections; Pneumonia, Viral; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Rhinovirus; Severity of Illness Index; Th1 Cells; Th2 Cells
PubMed: 31475732
DOI: 10.1002/jmv.25587 -
AAPS PharmSciTech Jul 2022Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective...
Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective therapeutic techniques. In this study, two kinds of cyclodextrin particles with typical particle shapes of nanocubes and microbars were synthesized through a facile process. Subsequently, the particles were used as carriers for loading and stabilizing iodine and characterizations were performed to demonstrate the loading mechanism. Next-generation impactor (NGI) experiments showed that iodine-loaded microbars (I@microbars) had a deposition rate of 79.75% in URT, while iodine-loaded nanocubes (I@nanocubes) were delivered to the deep lungs with a fine particle fraction (FPF) of 46.30%. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the iodine-loaded nanocubes and microbars had similar bactericidal effect to povidone iodine solution. Cell viability studies and extracellular pro-inflammatory factor (TNF-α, IL-1β, IL-6) evaluations demonstrate noncytotoxic effects of the blank carriers and anti-inflammatory effects of iodine-loaded samples. The irritation of the rat pharynx by I@microbars was evaluated for the behavioral observations, body weight changes, histopathological studies, and TNF-α, IL-1β, and IL-6 levels in pharyngeal tissues. The results showed that I@microbars had no irritation to rat pharyngeal tissues at therapeutic doses. In conclusion, the present study provides novel treatment of URT infections via supramolecular cyclodextrin carriers for URT local therapy with iodine loading by a solvent-free method, which enhances the stability and reduces the inherent irritation without inhibiting their antimicrobial effects. Two kinds of cyclodextrin particles with typical shapes of microbars and nanocubes were synthesized by a facile process. Subsequently, iodine was successfully loaded into the particles by gas-solid interaction. The iodine-loaded microbars showed air dynamics characteristics for inhalation delivery to the upper respiratory tract with little alveolar deposition in the lungs.
Topics: Administration, Inhalation; Animals; Cyclodextrins; Interleukin-6; Iodine; Particle Size; Pneumonia; Rats; Tumor Necrosis Factor-alpha
PubMed: 35804252
DOI: 10.1208/s12249-022-02277-x