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Biomedical subjects

Richard M Costanzo

Publications and source records attributed to Richard M Costanzo.

13 recordsLinked to original sources

Response of matrix metalloproteinase-9 to olfactory nerve injury.

Matrix metalloproteinases function in the remodeling of the extracellular matrix during growth and development as well as in injury and disease processes. We examined the role of matrix metalloproteinase-9 in a model of olfactory nerve injury in mice. We measured changes in matrix metalloproteinase-9 protein levels for up to 60 days following olfactory nerve transection. Matrix metalloproteinase-9 levels increased within hours after injury, peaked at day 1 and were elevated for approximately 2 weeks before returning to control levels over the 60-day time period. The increase in matrix metalloproteinase-9 was temporally associated with the degeneration of olfactory neurons that follows nerve transection and with increased gliosis. Our results demonstrate a temporal relationship between matrix metalloproteinase-9 elevation, degeneration of olfactory neurons and gliosis.

Animals↗

Cross-cultural comparison of data using the odor stick identification test for Japanese (OSIT-J).

A new olfactory test, the odor stick identification test for Japanese (OSIT-J), has been developed in Japan. To determine if the OSIT-J would be effective cross-culturally, we administered the test to 52 US and 50 Japanese subjects reporting normal olfactory function. The average composite OSIT-J test score for US subjects was significantly lower (77%) than that for Japanese subjects (94%, P < 0.0001). Both US and Japanese subjects correctly identified eight of the 13 odorants included in the OSIT-J with scores of 80% or higher. However, for five odorants, the US subjects' scores fell below 80% and were consistently lower than Japanese subjects, presumably reflecting cultural differences in odor experience. Most of the US subjects found the OSIT-J to be easy, interesting, pleasant, and short in duration. Although the 13-odorant OSIT-J was found to be suitable for testing US populations, elimination of five test odorants that were unfamiliar to US subjects significantly enhanced the test's effectiveness. Findings from this study emphasize the importance of identifying test odorants that may have a cultural bias, a crucial issue when comparing data obtained from different smell tests used at smell and taste centers around the world.

Adult↗

Posttraumatic olfactory loss.

Head injury is the leading cause of posttraumatic anosmia. Complete or partial loss of olfactory function may occur when the nasal passages are blocked, olfactory nerves are injured or there are contusions or hemorrhages in olfactory centers of the brain. Evaluation of patients with posttraumatic olfactory loss should include a physical examination by the otolaryngologist. Nasal endoscopy and radiological studies should be performed as well as olfactory function tests to determine the degree and type of olfactory impairment. Although treatment options may be limited, physicians should provide information and counseling regarding the risks and hazards associated with loss of olfactory function. For some individuals such as cooks, firefighters, and research scientists, an assessment of vocational activities should be performed prior to reentry into the workplace. Individuals with impaired olfactory function may be unable to detect important warning signs such as gas leaks, volatile chemical fumes and fires and therefore place themselves and coworkers at an increased risk for serious injury or death.

Craniocerebral Trauma↗

Toxic effects on gustatory function.

A large number of substances and disease processes may impact the sense of taste. Toxic substances may cause taste dysfunction from their effects on the gustatory system from the salivary gland, to the taste bud, to the central neural pathways. A number of external toxins, including industrial compounds, tobacco, and alcohol, may adversely affect taste, most commonly through local effects in the oral cavity. Blood-borne toxins, such as medications and those present in autoimmune and other systemic disorders (e.g. renal or liver failure), have access to all parts of the gustatory system, and thus may exhibit varied effects on taste function. An understanding of these potential toxins and their impact on gustation will help physicians better recognize, and potentially limit the impact of such taste alterations on their patients.

Diabetes Complications↗

Comparison of diagnostic findings using different olfactory test methods.

OBJECTIVE: To quantify discrepancies in the diagnosis of olfactory function that might exist when comparing results obtained from centers using different methods of olfactory testing. STUDY DESIGN: Prospective study of 50 healthy adult volunteers and 25 adult patients with olfactory complaints. METHODS: Two test methods, the Connecticut Chemosensory Clinical Research Center (CCCRC) test widely used in the United States, and the Jet Stream Olfactometer (JSO) test used in Japan, were used to measure and categorize the diagnostic level of olfactory function (normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, anosmia). Olfactory function was measured separately for each nostril. RESULTS: There was a significant correlation (rs = 0.788, P < .01, n = 150 nostrils) between diagnostic categories assigned by the CCCRC and JSO test methods. Diagnostic categories were identical for 66.7% of the nostrils tested, and in only 7.3% of the cases did the results differ by more than one category. For the anosmic and normosmic categories, test results were in agreement 91.7% of the time, whereas for the hyposmic categories (mild, moderate, and severe) results were in agreement only 22.2% of the time. CONCLUSIONS: Our results demonstrate that when comparing clinical or research data obtained from centers using different olfactory test methods, subjects with diagnoses of anosmia or normosmia may be more reliably compared than those with different levels of hyposmia.

Adolescent↗

Hazardous events associated with impaired olfactory function.

OBJECTIVE: To evaluate the risk of olfactory-related hazardous events in patients with impaired olfactory function. DESIGN: Retrospective cohort study. SETTING: A university-based clinic for smell and taste disorders. PATIENTS: A total of 445 patients who underwent olfactory testing between 1983 and 2001. INTERVENTIONS: Patient interview, olfactory testing. MAIN OUTCOME MEASURES: (1) Frequency of olfactory-related hazardous events including cooking incidents (ie, burning pots or pans), undetected fires, undetected gas leaks, and ingestion of spoiled foods or toxic substances; (2) level of olfactory function (anosmia; severe, moderate, or mild hyposmia; or normosmia) as determined by olfactory testing. RESULTS: Olfactory testing revealed that 76% of patients had some degree of impairment; 30% had complete anosmia. Thirty-seven percent of patients with olfactory impairment but only 19% of patients without impairment experienced at least 1 olfactory-related hazardous event. Of the hazardous events reported by impaired patients, cooking-related incidents were most common, representing 45%, with ingestion of spoiled food (25%), inability to detect a gas leak (23%), and inability to smell a fire (7%) reported less frequently. There was a significant correlation between frequency of hazardous events and degree of olfactory impairment (Cochran-Armitage trend test, P<.001): at least 1 hazardous event was reported by 45.2% of patients with anosmia, 34.1% with severe hyposmia, 32.8% with moderate hyposmia, 24.2% with mild hyposmia, and 19.0% of patients with with normal olfaction by testing. CONCLUSION: Patients with impaired olfactory function are more likely to experience olfactory-related hazardous events than those with normal olfactory function.

Accidents, Home↗

Effects of head injury on olfaction and taste.

Traumatic events such as motor vehicle accidents, falls, or assaults can lead to dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory dysfunction include direct injury to the sinonasal tract or olfactory epithelium, shearing effect on olfactory fibers at the cribriform plate, or brain contusion or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but may occur as a result of direct injury to the tongue, injury to cranial nerves VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients presenting with olfactory or gustatory complaints should include a thorough history, including assessment for pre-and posttraumatic chemosensory dysfunction and potential mechanisms of injury, complete head and neck examination including nasal endoscopy and cranial nerve testing, and focused radiographic imaging, usually CT of the sinuses and skull base. Formal olfactory and gustatory testing may be performed using various techniques, although in cases potentially involving litigation, methodologies able to detect malingering should be used. Treatable causes of chemosensory disturbance, most notably conductive olfactory losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled out. In the event of neurosensory deficits, recovery may occur up to 12 to 18 months after the traumatic event. All patients should be counseled regarding the risks of their chemosensory deficits, and given suggestions for appropriate compensatory strategies.

Brain↗

Remodeling of reciprocal synapses associated with persistence of long-term memory.

We investigated a model of long-term memory in which the female mouse establishes pheromonal memory of its partner at mating. We examined the reciprocal synapses of the accessory olfactory bulb and found that pheromonal memory was associated with morphological changes in excitatory synapses in the early phase of memory acquisition and by changes in inhibitory synapses in the late phases of memory persistence. After extinction of pheromonal memory, these morphological changes were no longer present. These findings suggest that the persistence of pheromonal memory is associated with continuous and dynamic changes in the morphological plasticity of reciprocal synapses in the accessory olfactory bulb.

Animals↗

Matrix metalloproteinase expression in the olfactory epithelium.

The olfactory epithelium contains neuronal progenitor cells capable of continuous neurogenesis and is a unique model for studying neural degeneration, regeneration, axon outgrowth and recovery from injury. Matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs), have been implicated in cell turnover, development, migration, and metastatic processes. We used Western blot and immunohistochemistry to determine whether MMP-2 and associated proteins TIMP-2 and membrane type 1 matrix metalloproteinase (MT1-MMP) are present in the olfactory epithelium of mice. We found MMP-2 expression localized to the olfactory basal cells and immature neurons. After injury-induced neural degeneration, MMP-2 and MT1-MMP levels decreased while TIMP-2 levels increased. However, following 35 days of neurogenesis and cell replacement TIMP-2 and MT1-MMP returned to control levels. The results show a correlation between MMP and TIMP levels and the stages of neural degeneration, regeneration and recovery of the olfactory epithelium following injury.

Animals↗

Detection thresholds for phenyl ethyl alcohol using serial dilutions in different solvents.

Detection thresholds are typically obtained by presenting a subject with serial dilutions of an odorant. Many factors, including the solvent used to dilute the odorant, can influence the measurement of detection thresholds. Differences have been reported in detection thresholds for phenyl ethyl alcohol (PEA) when different solvents are used. In this study we used gas chromatography (GC) to investigate further the effect of solvent on odor detection thresholds. We used a single ascending method and serial dilutions of PEA in four different solvents--liquid paraffin (LP), mineral oil (MO), propylene glycol (PG) and dipropylene glycol (DPG)--to determine the PEA thresholds for 31 adult subjects. For each solvent, we prepared eight serial log base 10 step dilutions (1-8), with corresponding liquid PEA concentrations of 6.3 x 10(1)-6.3 x 10(-6) (% v/v). We found that the threshold concentrations for PEA in LP (step 6.5) and PEA in MO (step 5.5) were significantly lower (P < 0.05) than for PEA in PG (step 4.0) and DPG (step 4.0) We then used GC to measure both the liquid and gas PEA concentrations for the dilution steps prepared with LP and PG. Although there were large threshold differences in the liquid concentrations of PEA in LP and PG, the headspace gas concentrations of PEA were the same. These results demonstrate the importance of determining the gas concentration of odorant stimuli when performing odor threshold measurements, in particular when comparing odor detection thresholds obtained using different solvents.

Adult↗

A comparative immunocytochemical study of development and regeneration of chemosensory neurons in the rat vomeronasal system.

Vomeronasal neurons undergo continuous neurogenesis during development and after neuronal injury. We used immunocytochemical methods to compare different stages of the vomeronasal organ development to those of regeneration following vomeronasal nerve transection. At E15 and at 6 to 10 days after injury, nestin-positive cells were observed throughout the sensory epithelium. We did not find nestin immunoreactivity to be localized to the boundary region of the epithelium. The early appearance and wide distribution of nestin-positive cells suggests that they represent chemosensory precursor cells that develop and migrate vertically in the epithelium. Vomeronasal receptor cells degenerated 6 to 8 days after nerve transection, but axon terminals in the accessory olfactory bulb (AOB) continued to show the presence of the chemosensory specific marker (OMP) for up to ten days, a significant finding observed in this study. It is likely that the distance from the site of nerve transection may contribute to differences in the time course of anterograde and retrograde axon degradation. OMP-positive neurons were observed in the normal adult epithelium and to a much lesser extent 10-60 days after recovery from nerve transection. Axons from regenerated receptor cells did not reach the AOB during this time period. This failure to reestablish connections with target cells in the AOB could explain why OMP-positive cells were rarely observed among the regenerated cells in the vomeronasal epithelium.

Aging↗