A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Frequency of BRAF V600E immunoexpression in ameloblastomas: a multi-institutional analysis of 86 cases in Latin America and comprehensive review of the literature.

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a differential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Incisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.

The surgical challenge of carotid artery and Fallopian canal dehiscence in chronic ear disease: a pitfall for endoscopic approach.

OBJECTIVE: Endoscopic procedures are becoming common in middle ear surgery. Inflammation due to chronic ear disease can cause bony erosion of the carotid artery and Fallopian canals, making them more vulnerable during surgery. The objective of this study was to determine whether or not chronic ear disease increases dehiscence of the carotid artery and Fallopian canals. DESIGN: Comparative human temporal bone study. SETTING: Otopathology laboratory. PARTICIPANTS: We selected 78 temporal bones from 55 deceased donors with chronic otitis media or cholesteatoma and then compared those two groups with a control group of 27 temporal bones from 19 deceased donors with no middle ear disease. MAIN OUTCOME MEASURES: We analysed the middle ear, carotid artery canal and Fallopian canal, looking for signs of dehiscence of its bony coverage, using light microscopy. RESULTS: We found an increased incidence in dehiscence of the carotid artery and Fallopian canals in temporal bones with chronic middle ear disease. The size of the carotid artery canal dehiscence was larger in the middle ear-diseased groups, and its bony coverage, when present, was also thinner compared to the control group. Dehiscence of the carotid artery canal was more frequently located closer to the promontory. The incidence of Fallopian canal dehiscence was significantly higher in temporal bones from donors older than 18 years with chronic middle ear disease. CONCLUSION: The increased incidence of the carotid artery and Fallopian canal dehiscence in temporal bones with chronic middle ear disease elevates the risk of adverse events during middle ear surgery.

The effects of solvents on embryonic stem cell differentiation.

Dimethyl sulfoxide (DMSO) and ethanol are common organic solvents used for dissolving lipophilic substances for in vitro testing. However, DMSO is known to induce differentiation in embryonic stem (ES) and embryonic teratocarcinoma (EC) cells. In order to clarify if solvents like DMSO and ethanol have an influence on in vitro developmental toxicity test systems, the presented study has evaluated their effects on differentiation by using different test systems. ES and EC cells were transfected with a construct containing the mTert promoter combined with the green fluorescent protein gene (GFP). A down-regulation of mTert, a marker for undifferentiated cells, results in a lower expression of GFP, which could be measured by flow cytometry. Taking the specific characteristics of ES and EC cells into account this effect could be a hint for the interaction of DMSO with embryonic development. Additionally, the effects of the solvents ethanol and DMSO on Oct-4 expression, another marker for undifferentiated cells, were measured in wild-type ES cells. Both selected molecular markers demonstrated an induction of differentiation after exposure to DMSO; in wild-type ES cells at a concentration of 0.125% and in transgenic EC cells at a concentration of 0.25% DMSO. All other differences from controls, including those which attained a level of statistical significance, were minor or not dosage related in degree, or were not consistent over time and are, therefore, considered to be of little toxicological importance. In addition, a cytotoxicity test demonstrated that the solvents affected the employed molecular markers in non-cytotoxic concentrations. The ES cells were the most sensitive towards the cytotoxic effects of the solvent DMSO while the EC cells were more sensitive when treated with the solvent ethanol.

Results of a round-robin exercise on read-across.

A round-robin exercise was conducted within the CALEIDOS LIFE project. The participants were invited to assess the hazard posed by a substance, applying in silico methods and read-across approaches. The exercise was based on three endpoints: mutagenicity, bioconcentration factor and fish acute toxicity. Nine chemicals were assigned for each endpoint and the participants were invited to complete a specific questionnaire communicating their conclusions. The interesting aspect of this exercise is the justification behind the answers more than the final prediction in itself. Which tools were used? How did the approach selected affect the final answer?

Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity.

Although pulmonary infections caused by Pseudomonas aeruginosa can hardly be eradicated in patients with cystic fibrosis (CF, the most common genetic disease among Caucasians), these patients are mainly treated with intravenous and nebulized tobramycin. Long-term treatment with tobramycin, however, may induce ototoxic effects. We assessed the clinical histories and postmortem temporal bones of six patients with CF for signs of this ototoxicity. Four bones showed typical manifestations of ototoxicity induced by aminoglycosides (AGs): loss of hair cells in the lower turns, and degeneration of ganglion cells. Six bones revealed no loss or scattered loss of hair cells, however, degeneration of the spiral ganglion cells was observed. This suggests that degeneration of the spiral ganglion may occur as a primary manifestation in some cases of ototoxicity due to aminoglycosides. Recent reports have shown that trophic factors (neurotrophins and acidic fibroblast growth factor) interacting with hair cells and the spiral ganglion protect the inner ear from damage. It may be that disturbances in supply of such trophic factors caused degeneration of ganglion cells without loss of hair cells in the cases we studied.

Mastoidectomy update.

The long-term results of 375 primary mastoidectomy operations for chronic otitis media and chronic mastoiditis are described and discussed. Two-thirds of these cases were open cavity mastoidectomies and 1/3 closed cavity mastoidectomies. Primary pathology was cholesteatoma in 1/3 and granulation tissue in 2/3 of the cases. The method of reducing the size of the mastoid cavity by sculpturing mastoid cavity by sculpturing mastoid cortical bone is most important in avoiding large postoperative cavity problems. Principles and methods are described. Healing (dry ear) is a more important management objective than hearing and, indeed, enhances the prospects of obtaining a long-term hearing result. Three important phases of controlling mastoid disease (preoperative, operative, and postoperative) are equally stressed. Intact wall tympanomastoidectomy is not recommended in sclerotic mastoids (the majority of our cases) as being unsafe and unnecessary. Revisions, mostly minor, were done in 31% of the cases for a total of 521 procedures. We recomment a one-stage tympanomastoidectomy. Multiple planned procedures are, in the main, unnecessary and should be avoided to reduce unnecessary hospitalization and expense.

Endolymphatic sac drainage for intractable vertigo (method and experiences).

This paper describes a method of endolymphatic sac decompression and drainage. The method emphasizes widely exposing dura, avoiding skeletonization of the posterior semicircular canal and draining the sac via a T tube. The results of this procedure in 75 patients, including statistics in 46 ears are discussed. In patients with unilateral disease good results were obtained in control of vertigo in 94 percent of patients and significant improvement in cochlear function in over 30 percent.

Presbycusis: what is it?

The history and current misusage of the term presbycusis is discussed and current knowledge of pathology associated with presbycusis and aging are reviewed. A study involving retrospective analysis of audiometric data and clinical information on three groups was performed. Results suggest that a group of individuals previously identified as "presbycusic" probably represent undiagnosed cases of familial or genetic related hearing loss. We urge as thorough an identification of correct diagnosis as possible, thus reserving the term "presbycusis" for those rare, soley age-related cases of sensorineural loss.

Exploratory tympanotomy revisited.

The history of exploratory tympanotomy is somewhat obscure. Methods and findings of exploratory tympanotomy were described and assessed for unexplained conductive and occasional sensorineural hearing losses. Of 316 recent cases positive findings leading to diagnosis and therapy occurred in all 250 cases of conductive hearing losses and in 43 of 63 cases of sensorineural hearing losses. In decreasing order of occurrence findings were sequelae of otitis media, otosclerosis, oval and round window changes including perilymph leakage, congenital and traumatic fixation and disarticulation of ossicles. These observations and indications are discussed.

Experience with tympanoplasty for atelectatic ears.

Atelectasis is, unfortunately, still a common sequela of otitis media with effusion (OME)--including serous otitis media (SOM) and mucoid otitis media (MOM). When atelectatic ears provide a functional deficit, i.e., a conductive loss of sufficient magnitude or a residual conductive loss after aerating the middle ear with ventilation tube or early or strongly suspected attic cholesteatoma, a simple corrective procedure has been used which has stood the test of time. The procedure as well as experience with 51 patients (60 ears) will be described and discussed. The procedure consists of re-establishing the mesotympanic space, strengthening the tympanic membrane by an underplant fascial graft, cutting the tensor tympani, extirpation of any disease, re-establishment of ossicular mobility and continuity and the insertion of a ventilation tube in the anterior drumhead remnants along with silicone rubber sheeting and a moist Gelfilm implant. Methods and results are discussed.

Trauma and Meniere's syndrome.

Thirty-seven patients who developed Meniere's syndrome following acoustic (18) and physical (19) trauma are described and discussed. Histopathologic characteristics, which appear identical to idiopathic Meniere's disease, are described in a gentleman who developed Meniere's syndrome after head trauma. Concepts of cause and effect relationships and pathogenesis are discussed.

Air caloric testing in otitis media. (preliminary studies).

On certain occasions it becomes important to evaluate vestibular function in a patient with otitis media. The potential application of the air caloric test in evaluating such patients was examined. Patients with unilateral otitis media before and after surgery were studied to answer certain clinical questions. More questions were raised than answers provided. The preliminary conclusions from this study are: 1. Patients with tympanostomy tubes or small perforation of one ear may show a caloric response in the perforated ear equal to that of the intact ear. 2. Patients with a large tympanic membrane perforation on one side may show hyperactive caloric responses on the perforated side. 3. Patients with a moist ear may show inverted horizontal nystagmus to warm air caloric testing. This applies to patients with a large perforation or mastoidectomy cavity. 4. Patients with a dry open mastoid or fenestration cavity are likely to show a hyperactive caloric response on the side of previous surgery, accompanied by vegetative symptoms. This size of the cavity appears to be less important than the presence of the cavity per se. 5. Patients may be safely tested in the early postoperative period.

Ménière's disease in children.

Approximately 3% of all patients with Meniere's disease are in the pediatric age group. These children require extensive evaluation. A history of physical or acoustic trauma should be sought and an allergic work-up should be obtained. A search for metabolic disturbances and identification of inflammatory disorders is also necessary. If a treatable etiology is identified, specific therapy should be directed toward its control. If, after careful evaluation, the etiology remains obscure, non-specific therapy should be instituted in an effort to alleviate the symptomatology of Meniere's disease. Surgical decompression of the endolymphatic sac and drainage into the mastoid cavity results in relieving the symptoms, particularly vertigo, and appears to be efficacious in patients who have failed diligent attempts at medical therapy.

Otosclerosis and Meniere's syndrome: diagnosis and treatment.

Occasionally a patient with otosclerosis and a conductive hearing loss will develop typical findings of Meniere's syndrome in the involved ear, years later. A review of clinical and pathological studies in the literature and in our laboratory and clinic indicates a likely cause-and-effect relationship for these cases. The pathology and pathogenesis of the syndrome of otosclerosis and Meniere's syndrome is discussed. A stapedectomy/sacculotomy was used to treat 17 patients, 13 of whom acquired a satisfactory result in terms of improvement of hearing and control of vertigo. This technique and findings are described and discussed.

Meningiomas of the temporal bone.

Meningiomas should be considered in the differential diagnosis of otologic tumors arising from the middle ear and mastoid. It is generally recognized that meningiomas may invade the temporal bone via direct extension from the intracranial space (secondary). It is not generally recognized that meningiomas can develop initially in the middle ear cleft (primary). Representative cases of primary and secondary meningiomas of the temporal bone are described and clinical aspects of diagnosis surgical management are discussed. In order to assess the pathogenesis of meningiomas of the temporal bone, histological studies were done on 200 temporal bone specimens. In certain specimens, ectopic arachnoid granulations, from which primary meningiomas may originate, were identified and described, according to location. One specimen was most unusual in that it contained ectopic glial as well as arachnoidal tissue.

Mastoiditis and brain hernia (mastoiditis cerebri).

Ten patients with brain hernia occurring as an insidious complication of chronic mastoiditis coincidentally discovered at the time of surgery are described. Four had previous surgery, six did not. A history of trauma was othwise absent. Cerebrospinal fluid otorrhea did not occur. Our method of management is described. Pathology and pathogenesis are discussed. Three patients had pedunculated brain hernias, while seven had diffuse (fungoid) herniation. Granulation tissue appeared as an important part of the disease process. These may represent abortive attempts at brain abscess formation since the widespread use of antibiotics. Pacchionian bodies may also play a role in the pathogenesis.

Histopathology of sudden hearing loss.

Eleven temporal bones from eight patients who had clinical histories of sudden hearing loss (SHL) were studied to assess the possible etiopathogenesis. The origin of SHL in seven ears from five patients was obscure, but appeared to be due to multiple causes. Common histopathologic changes in the cochlea, although complex, included atrophy of the organ of Corti and loss of cochlear neurons. Loss of cochlear neurons was the main finding in ears of viral infection. Labyrinthine fibrosis and formation of new bone were seen in two ears associated with vascular insult and in two ears of autoimmune disease. Different histopathologic findings causing SHL were observed even in cases with the same etiology. A case of SHL showing endolymphatic hydrops as the main histopathologic finding is described.

Prevalence of facial canal dehiscence and of persistent stapedial artery in the human middle ear: a report of 1000 temporal bones.

A total of 1000 temporal bones were used to study the prevalence of facial canal dehiscence and of persistent stapedial artery in detail. Of the temporal bones studied, 560 (56%) contained at least one facial canal dehiscence. There was a 76.3% prevalence of bilaterality of this canal wall gap. The most common site of dehiscence was the oval window area. The concept of microdehiscence of the facial canal is introduced. One third of the temporal bones observed had a microdehiscence of the facial canal, usually located at the oval window area (74.9%) and found bilaterally 40% of the time. The authors found a 0.48% prevalence (5 out of 1045) of persistent stapedial artery. This is the first histological study of temporal bones to report a prevalence of this vascular anomaly.

Experimental grafting of the round window membrane: Part I.

The histology and permeability of cats' round window membranes were described following surgical grafting with gelatin foam or fascia. An increase in the thickness of the round window membrane due to fibrosis, neovascularization, and epithelial metaplasia was observed 2 months following grafting with gelatin foam. Grafting with fascia did not increase the thickness of the round window membrane, but did form a thick layer of granulation tissue adjacent to and overlying the window membrane, with occasional adhesions between. The layer of granulation tissue consisted of cuboidal or columnar ciliated epithelial cells, fibrous tissue, lipid, and undigested grafted material. The granulation tissue did not always completely cover the round window membranes.