Post-traumatic anosmia. Ultrastructural correlates.

Five patients suffering post-traumatic anosmia were studied at the University of Colorado Health Sciences Center, Denver. Each patient underwent psychophysical testing, clinical evaluation, and olfactory biopsy. The biopsy specimens were examined ultrastructurally and were found to vary from normal tissues. The overall appearance of the olfactory epithelium in the post-traumatic patient is disrupted and the receptor cells are distorted. Large numbers of axons are located near the basement membrane and can often be found in bundles throughout the epithelium, extending even to the mucosal surface. Olfactory cilia are rarely seen in epithelia obtained from post-traumatic patients. Bald olfactory vesicles, often containing basal bodies, are frequently observed. We postulate that in these cases, the olfactory epithelium regenerates following head trauma and the receptor cells attempt to send axons centrally. However, the cribriform plate has undergone fibrotic healing and the axons are unable to penetrate it and make contact with olfactory bulb neurons.

The vomeronasal (Jacobson's) organ in man: ultrastructure and frequency of occurrence.

These investigations address three major questions: (1) What is the frequency of occurrence of the vomeronasal (Jacobson's) organ (VNO) in man? (2) what is the ultrastructure of the human VNO? and (3) does the VNO contain sensory receptor cells? Macroscopic and microscopic intranasal clinical examinations of over 200 persons revealed paired bilateral vomeronasal pits on the anterior 1/3 of the nasal septum in all cases. Biopsies of the vomeronasal pits and surrounding tissues were examined by light and electron microscopy. These studies showed that the vomeronasal pit leads to a closed tube, 2-8 mm long, lined by a unique pseudostratified columnar epithelium unlike any other in the human body. The anterior end of the tube is lined by tall, columnar cells with a sparse population of short microvilli. The posterior end of the VNO is lined by an epithelium that contains three morphologically distinct cell types: (1) basal cells; (2) "dark cells--tall, slender cells with heterochromatic nuclei and electron-dense cytoplasm that often contain mucigen-like granules; and (3) "light" cells--large, clear cells, extending from the basement membrane to the organ's lumen. Each "light" cell has a round, euchromatic nucleus and a clear cytoplasm that often contains many Golgi stacks and membrane-limited vesicles filled with material of modest electron density. The cell apex is tipped by a few short microvilli. Whether these cells subserve any sensory function awaits further investigation.

Ultrastructural neurobiology of the olfactory mucosa of the brown trout, Salmo trutta.

This paper describes four investigations of the olfactory mucosa of the brown trout: 1) the ultrastructure of the olfactory mucosa as revealed by scanning (SEM), conventional transmission (TEM), and high voltage (HVEM) electron microscopy; 2) light and electron-microscopic investigations of retrograde transport of the tracer macromolecule horseradish peroxidase (HRP) when applied to the cut olfactory nerve; 3) SEM and TEM investigations of the effects of olfactory nerve transection on cell populations within the olfactory epithelium; and 4) ultrastructural investigations of reversible degeneration of olfactory receptors caused by elevated copper concentrations. The trout olfactory epithelium contains five cell types: ciliated epithelial cells, ciliated olfactory receptor cells, microvillar olfactory receptor cells, supporting cells, and basal cells. The ciliated and microvillar olfactory receptor cells and a small number of basal cells are backfilled by HRP when the tracer is applied to the cut olfactory nerve. When the olfactory nerve is cut, both ciliated and microvillar olfactory receptor cells degenerate within 2 days and are morphologically intact again within 8 days. When wild trout are taken from their native stream and placed in tanks with elevated copper concentrations, ciliated and microvillar cells degenerate. Replacement of these trout into their stream of origin is followed by morphologic restoration of both types of olfactory receptor cells. Ciliated and microvillar receptor cells are primary sensory bipolar neurons whose dendrites make contact with the environment; their axons travel directly to the brain. Consequently, substances can be transported directly from the environment into the brain via these "naked neurons." Since fish cannot escape from the water in which they swim, and since that water may occasionally contain brain-toxic substances, the ability to close off--and later reopen--this anatomic gateway to the brain would confer a tremendous selective advantage upon animals that evolved the "brain-sparing" capacity to do so. Consequently, the unique regenerative powers of vertebrate olfactory receptor neurons may have their evolutionary origin in fishes.

Ultrastructural histopathology of human olfactory dysfunction.

This paper presents electron-microscopic observations on biopsies of the olfactory mucosae of several classes of patients with smell disorders: 1) patients with loss of smell function following head injury (post-traumatic anosmics or hyposmics); 2) patients with loss of smell function following severe head colds and/or sinus infections (post-viral olfactory dysfunction, or PVOD); and 3) patients that have lacked smell function since birth (congenital anosmics). Of these, the traumatic anosmics' olfactory epithelia were quite disorganized; the orderly arrangement of supporting cells, ciliated olfactory receptor neurons, microvillar cells, and basal cells was disrupted. Although many somata of ciliated olfactory receptors were present, few of their dendrites reached the epithelial surface. The few olfactory vesicles present usually lacked olfactory cilia. The post-viral anosmics, too, had a greatly reduced number of intact ciliated olfactory receptor neurons, and most of those present were aciliate. The post-viral hyposmics had a larger population of intact, ciliated olfactory receptor cells. In the seven cases of congenital anosmia studied, no biopsies of olfactory epithelium were obtained, indicating the olfactory epithelium is either absent--or greatly reduced in area--in these individuals.

Electron microscopy of human olfactory epithelium reveals a new cell type: the microvillar cell.

The olfactory epithelium of mammals is generally considered to consist of 3 cell types: basal cells, supporting (sustentacular) cells, and ciliated olfactory receptors. We have completed a detailed ultrastructural study of the fine structure of the human olfactory mucosa. In our electron microscopic observations of biopsies of human olfactory epithelium taken from normal, consenting volunteers under local anesthesia, we have consistently observed a fourth cell type, the microvillar cell, located near the epithelial surface. The apical end of these flask-shaped, electron-lucent cells gives rise to a tuft of microvilli that project into the mucus layer lining the nasal cavity. The cell body itself contains bundles of microfilaments, mitochondria, a well-developed smooth endoplasmic reticulum, a prominent Golgi complex, electron-dense vesicles that resemble lipofuscin granules, free ribosomes, and occasional cisternae of the rough endoplasmic reticulum. A thin, axon-like cytoplasmic process extends from the basal pole of the cell and travels through the epithelium toward the lamina propria. Although there is no physiological evidence that bears upon the function of the microvillar cell, its ultrastructure suggests it may be a bipolar sensory neuron. Based upon morphological and phylogenetic considerations, the authors speculate the microvillar cell represents a second morphologically distinct class of chemoreceptor in the human olfactory mucosa.

Calbindin-like immunoreactivity in epithelial cells of the newborn and adult human vomeronasal organ.

The vomeronasal organs (VNOs) of two humans, a male neonate and a female adult, were examined for immunolocalization of calbindin-D28k (calbindin) which has been immunolocalized to VNO receptor cells in other mammals. The present study demonstrates that epithelial cells within the VNOs of both subjects expressed calbindin-like immunoreactivity. These results suggest that human VNO epithelial cells of both genders express calbindin during development and in the adult.

Peroxidase backfills suggest the mammalian olfactory epithelium contains a second morphologically distinct class of bipolar sensory neuron: the microvillar cell.

The olfactory epithelium of man, rat and some other mammals consists of 4 cell types: ciliated olfactory receptors, microvillar cells, supporting (sustentacular) cells, and basal cells. Of these, the microvillar cell is least well understood: its function is unknown. In this study, a hypothesis is put forth: that the microvillar cells in the mammalian olfactory epithelium comprise a morphologically distinct class of sensory receptor. The hypothesis is tested by injecting the cytochemical tracer macromolecule horseradish peroxidase (HRP) into the olfactory bulb of the rat, and observing its pattern of uptake in the olfactory epithelium by light and electron microscopy. In these experiments, ciliated olfactory receptors and microvillar cells backfilled with HRP: supporting and basal cells did not. The data, which support the hypothesis, indicate the microvillar cells, along with the ciliated olfactory receptors, send axons to the olfactory bulb. Consequently, it is concluded that the microvillar cell is a sensory bipolar neuron, with the cell body in the olfactory epithelium, that sends a dendrite to the site of stimulus reception at the free surface of the olfactory epithelium, and an axon to the olfactory bulb in the brain. The similarity of microvillar cells in the olfactory epithelium to 'brush cells' found throughout the respiratory tract is discussed in detail.

Calbindin-like immunoreactivity in two peripheral chemosensory tissues of the rat: taste buds and the vomeronasal organ.

In the rat, calbindin-like immunoreactivity was observed at both the light and electron microscopic levels within the chemoreceptor neurons of the vomeronasal organ (VNO) and both intragemmal cells and associated nerve fibers of the circumvallate taste buds. All VNO neurons were immunoreactive. Only a subset of intragemmal taste cells was immunoreactive; associated immunoreactive nerve fibers were apposed to both labeled and unlabeled cells but no synaptic contacts were observed.

Juvenile nasopharyngeal angiofibroma: management of intracranial extension.

Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally invasive tumor of the nasopharynx that is found primarily in the pubescent male. While most authors recommend surgical excision for smaller, localized extracranial tumors, opinion varies on the management of more aggressive tumors with intracranial extension. The authors present their experience over the past 15 years with 15 cases of JNA with intracranial extension, and formulate a plan of management. A combined otolaryngologic/neurosurgical approach is recommended in order to assess the extent of the tumor and to isolate feeding vessels. Lateral extension into the middle cranial fossae should be resected in continuity with the nasopharyngeal component, which is approached from below in a separate operative field. Medial extensions are transected, verified angiographically three months after surgery, and irradiated. The results of therapy are presented, and a case of dural penetration by JNA is described.

Protein gene product 9.5 in the developing and mature rat vomeronasal organ.

Protein gene product 9.5 (PGP 9.5) was immunocytochemically identified in structures of the developing and mature rat vomeronasal organ (VNO). This study started with embryos at 17 days of gestation. By this stage, PGP 9.5 was immunolocalized within both the receptor cells of the neuroepithelium and cells of the receptor-free epithelium, located on the opposite side of the lumenal space. Nerve fibers surrounding the nascent vomeronasal vein also showed PGP 9.5 immunoreactivity. Labeling was retained in the neuroepithelium and nerve fibers around the vein during development and into adulthood. Within the pool of receptor cells of the adult neuroepithelium, labeling was observed within the cytoplasm of the somata and dendrites; some receptor cells also expressed nuclear labeling. The number of immunoreactive cells in the receptor-free epithelium appeared to increase postnatally but by adulthood immunoreactivity virtually was absent. These results suggest a role for PGP 9.5 in development and maturation of the VNO and a continuing role within the steadily renewing receptor cell population found in the mature neuroepithelium. The findings of this study also suggest that PGP 9.5 is localized within the nerve fibers surrounding the vomeronasal vein from early in development through adulthood.

Distribution of OMP-, PGP 9.5- and CaBP-like immunoreactive chemoreceptor neurons in the developing human olfactory epithelium.

We have examined the distribution of olfactory marker protein (OMP), protein gene product 9.5 (PGP 9.5) and calcium-binding protein D-28k (CaBP) in the olfactory epithelium of mid- to late fetal and newborn humans using immunocytochemistry. Olfactory chemoreceptor neurons (ORNs) in a 24-week-old female fetus, a 31-week-old male fetus and a newborn male were examined. OMP-like immunoreactivity (-LI) and PGP 9.5-LI were distributed throughout ORNs at all ages. CaBP-like immunoreactivity, however, was found only in clustered or isolated fetal ORNs; in the newborn, CaBP-LI was seen only in isolated ORNs sparsely distributed throughout the OE. These findings demonstrate that human ORNs express OMP-LI nearly 4 weeks earlier in development than previously reported. PGP 9.5-LI is coincidentally abundant within these cells, suggesting it may have an important role in mature ORNs. Because the number of ORNs expressing CaBP-LI decreases during perinatal development, CaBP may be important in intracellular calcium regulation during ORN growth and maturation in the developing OE.

Ultrastructure of human nasal mucosa.

This thesis describes the ultrastructure of human nasal mucosa, based upon surgical biopsy specimens. The intent of the study is to characterize the normal ultrastructure of human nasal mucosa with emphasis upon the difference between olfactory and respiratory epithelia. Other nasal epithelia (anterior, sinus, and posterior) are reviewed briefly for comparison only. Several pathological examples of the olfactory and respiratory epithelia are also briefly presented for contrast.

Elective carotid artery resection for advanced squamous cell carcinoma of the neck.

The authors performed a retrospective review of their 10-year experience of carotid artery resection without revascularization for advanced squamous cell carcinoma of the neck. From 1982 to 1991, seven patients underwent elective carotid artery resection without reconstruction at the University of Colorado Health Sciences Center in Denver. A vascular clamp with gradual carotid occlusion was placed preoperatively on four patients and awake temporary balloon occlusion of the carotid was used on three patients. The primary lesions were three laryngeal carcinomas, two oral cavity carcinomas, and two hypopharyngeal carcinomas. All seven resected specimens showed invasion of the carotid fascia on pathological exam, while five specimens exhibited actual destruction of the arterial wall. Cerebrovascular accidents occurred in two patients (one immediate and one delayed), and the perioperative mortality was 29% (one cerebrovascular accident and one gastrointestinal bleed). The five remaining patients died of locoregional recurrence or metastatic disease within 1 year after their carotid artery resection. Resection of the common or internal carotid artery without reconstruction has a significant morbidity and mortality. This operation did not improve the long-term survival in our limited series of patients who presented with histologically proven invasion of the carotid artery.

Bronchial adenoma: a malignant misnomer.

Bronchial adenomas are a histologically and clinically diverse group of respiratory tract neoplasms arising from mucous glands and ducts of the tracheobronchial tree. They represent 1% of pulmonary malignancies. The traditional concept of a single, histologically benign form is challenged and the malignant potential of these tumors is stressed. Three main cell types with their characteristic histopathologic and clinical features are discussed: carcinoid, adenoid cystic carcinoma, and mucoepidermoid carcinoma. A case of bronchial carcinoid with hepatic metastases is reported, emphasizing the malignant potential of this controversial group of tumors. The appropriate diagnostic evaluation is outlined and aggressive surgical management is stressed. Chemotherapy and radiation therapy which are reserved mainly for palliation do not add to overall five year survival rates.

The intraoperative management of the thyroid gland during laryngectomy.

The standard of care of laryngeal cancer surgery is wide field excision of the larynx combined with ipsilateral thyroid lobectomy. A retrospective review of 247 laryngectomies performed between 1979 and 1989 was undertaken to determine specific intraoperative indications for thyroid gland removal. The incidence of thyroid disease in our patients with laryngeal cancer was compared to the normal population. Eight percent of thyroid specimens removed during laryngeal cancer surgery demonstrated invasion by squamous cell carcinoma. All patients having thyroid invasion had T3 or T4 laryngeal lesions that were stage IV at the time of surgery. All these lesions were found to have transglottic growth and laryngeal cartilage invasion by the pathologist. All of these patients also had abnormal thyroid glands intraoperatively and laryngeal cartilage destruction that was evident intraoperatively. Total thyroidectomy with bilateral paratracheal and pretracheal lymph node dissection is indicated when squamous cell carcinoma of the larynx involves the thyroid gland. Prophylactic ipsilateral thyroid lobectomy and isthmusectomy is warranted for large laryngeal cancers (T3, T4) that involve the anterior commissure, the subglottic area, or extend transglottically. Routine thyroid gland removal is not indicated for the majority of laryngeal cancers that do not meet the aforementioned criteria. Finally, abnormal thyroid histopathology was diagnosed in 37% of the surgical thyroid gland specimens removed during laryngectomy.

An optimal choice: home intravenous hydration after tonsillectomy.

Most tonsillectomies are performed as outpatient procedures in an ambulatory care facility. The postoperative period can be protracted, which can cause dehydration and readmission to the hospital. Timely intervention with home intravenous (IV) hydration can help prevent this complication. A prospective clinical trial was designed to evaluate the benefit of home IV therapy after tonsillectomy. One hundred consecutive patients underwent tonsillectomy. Fifty returned home without home IV hydration and another 50 returned home with home IV hydration. Clinical data were collected by the homecare nurse during the postoperative period. Comparison between these two groups showed that the patients with home IV hydration had less morbidity. Daily assessment of the patient by telephone is the best screening method to determine the need for IV hydration for the posttonsillectomy patient.

Transbronchial drainage of pulmonary abscesses with the flexible fiberoptic bronchoscope.

Flexible fiberoptic bronchoscopy with multiplanar fluoroscopic control is shown to be effective in the transbronchial drainage of pulmonary abscesses. A new technique which permits the intracavitary placement of brush forceps and fine arterial catheters is described. This has facilitated the rapid defervescence of fever and established immediate endobronchial drainage. Seventy percent of patients had complete radiographic closure of their abscess cavities at three months. Clinical findings are presented and the role of aspiration in pathogenesis of pulmonary abscess is stressed.

Middle ear effusions in neonates.

Suppurative middle ear effusions (MEE) have been shown to occur commonly in neonates. In spite of this, otoscopy is not routinely performed on septic infants in the neonatal intensive care unit (ICU). This is clinically significant since unrecognized suppurative MEE may act as a focus for dissemination of bacteria into the circulation and/or central nervous system (CNS). We have completed a prospective study in an attempt to define the prevalence, bacteriology, and response to therapy of MEE in neonates. To facilitate this, the normal micro-otsocopic appearance of the newborn TM was established by systematically examining 50 normal infants under 24 hours old. MEE was present in 30% of 125 consecutively examined infants in the neonatal ICU. Bacteriologic data are drawn from tympanocentesis performed on 34 neonates. Nasotracheal intubation of longer than seven days is highly associated with suppurative MEE. Suppurative MEE in the neonatal ICU is often refactory to treatment and may require prolonged therapy and repeated tympanocentesis.

Recurrent psychogenic coma following tracheal stenosis repair.

Medication, intracranial hemorrhage, infarction, infection, hypoxia, organ failure, and nutritional deficiency may cause unconsciousness following successful emergence from anesthesia. A 39-year-old woman with a history of tracheal stenosis, depression, and anxiety had complete unconsciousness on 3 separate occasions following surgical repair of her tracheal stenosis. In each case, the patient's endotracheal tube had been removed; she was alert and oriented to person, time, and place; and she was admitted to the hospital for observation. Within a few hours after the tube was removed, the patient became abruptly unconscious for periods of 36, 18, and 30 hours. Each time, the results of cardiac, pulmonary, metabolic, and neurologic examinations and radiological studies were normal. We hypothesize that the patient's apparent comas were the result of an underlying conversion disorder precipitated by unresolved psychological conflict surrounding a long history of abuse in which she was repeatedly smothered by a pillow.

Steroid-dependent anosmia.

In steroid-dependent anosmia (nasal polyps, inhalant allergy, anosmia), high doses of steroids will temporarily restore the sense of smell, a diagnostic test. Appropriate surgery can then be carried out, followed by low-dose, long-term steroid therapy to maintain the sense of smell. Olfactory biopsy specimens taken during the course of evaluation and treatment show electron-optically normal olfactory receptors, meaning that the probable pathogenesis of the sensory deficit is an obstruction, mechanical and possibly biochemical. Two cases of steroid-dependent anosmia are presented to detail a fully reversible anosmia using state-of-the-art techniques.