Fast and accurate measurement of taste and smell thresholds using a maximum-likelihood adaptive staircase procedure.

This paper evaluates the use of a maximum-likelihood adaptive staircase psychophysical procedure (ML-PEST), originally developed in vision and audition, for measuring detection thresholds in gustation and olfaction. The basis for the psychophysical measurement of thresholds with the ML-PEST procedure is developed. Then, two experiments and four simulations are reported. In the first experiment, ML-PEST was compared with the Wetherill and Levitt up-down staircase method and with the Cain ascending method of limits in the measurement of butyl alcohol thresholds. The four Monte Carlo simulations compared the three psychophysical procedures. In the second experiment, the test-retest reliability of MLPEST for measuring NaCl and butyl alcohol thresholds was assessed. The results indicate that the ML-PEST method gives reliable and precise threshold measurements. Its ability to detect malingerers shows considerable promise. It is recommended for use in clinical testing.

Splenic rupture: an unusual complication of colonoscopy.

Splenic rupture is an uncommon complication of colonoscopy. A high index of suspicion is a crucial factor in the prompt diagnosis of this rare but potentially fatal complication. We report a case of splenic rupture diagnosed 3 days after a colonoscopy and requiring splenectomy. We also reviewed 17 reported cases of splenic rupture after colonoscopy, including our case. The presumed mechanisms of splenic rupture during colonoscopy are direct trauma to the spleen, excessive splenocolic ligament traction, and decrease in the relative mobility between the spleen and the colon. Of the 17 cases reviewed, 10 had polypectomy and/or biopsy performed during colonoscopy. Other probable risk factors are identified and tabulated. The hemodynamic status of the patient is the primary factor used to determine the therapeutic option. Computed tomographic (CT) scan of the abdomen reliably demonstrates well-contained splenic laceration and subcapsular hematoma, and differentiates these splenic complications from perisplenic clot and hemoperitoneum. Thus, CT scan may help decide which patients may be managed operatively or nonoperatively. Splenectomy is the operative procedure of choice for splenic rupture after colonoscopy. Conservative management includes broad spectrum antibiotics, intravenous fluids, blood transfusion, and close hemodynamic monitoring. The factors mandating further evaluation of persistent abdominal pain after colonoscopy are hemodynamic instability, clinical features of acute abdomen, leukocytosis, and/or acute anemia. The onset of abdominal pain associated with one or more of these critical factors is usually within 24 h after colonoscopy. An emergent CT scan of the abdomen is the modality of choice to further evaluate these clinical features, but intestinal perforation and external bleeding must first be excluded.

Protein gene product 9.5-like and calbindin-like immunoreactivity in the nasal respiratory mucosa of perinatal humans.

BACKGROUND: Protein gene product 9.5 (PGP) and calbindin-D28k (calbindin) are neuroendocrine markers that have been localized to neuroendocrine cells in the developing tracheobronchial epithelium. Neuroendocrine cells may play some role in the development of the tracheobronchial epithelium. Little is known about the development of the nasal respiratory epithelium (RE). METHODS: Nasal respiratory mucosa from fetal and newborn humans was examined to determine immunoreactivity for PGP and calbindin. RESULTS: At all stages studied, cells of different morphologies displayed PGP-like immunoreactivity (-LI) and calbindin-LI. Columnar immunoreactive cells for both markers predominated, but labeled cells of different shapes were also observed. Most labeled columnar cells were in the RE at its border with olfactory epithelium (OE); a few similarly labeled columnar cells also appeared in this OE. In the lamina propria, PGP-LI was also seen in numerous thin branching fibers. Some of these branches penetrated into the epithelium, where fiber varicosities appeared to contact cells, some of which also exhibited PGP-LI. CONCLUSION: This study demonstrates that during development the human nasal RE contains different cell types, as illustrated by the assortment of epithelial cells displaying PGP-LI and calbindin-LI among unlabeled cells. Because PGP and calbindin immunoreactivities were found within neuroendocrine cells in previous studies, the present results indicate that the developing human nasal RE also may support a number of neuroendocrine cells. Furthermore, at least some of these cells may form synaptic contacts with nerve fibers from outside the epithelium.

Summary of the NIOSH guidelines for air sampling and analytical method development and evaluation.

Suggested guidelines for the development and evaluation of sampling and analytical methods for industrial hygiene monitoring have recently been published in a NIOSH technical report. These guidelines are based in part on various published approaches for method development and evaluation and serve as an attempt at a more unified experimental approach. This paper presents some salient features of this unified approach for method development and evaluation. The basic goal of the approach is to determine if the method under study meets the criterion to produce a result that fell within 25% of the true value 95 times out of 100 on average, although other factors of method performance are evaluated. The experiments proposed for the evaluation of method performance include determination of analytical recovery from the sampler, sampler capacity, storage stability of samples and effect of environmental factors. Evaluation criteria for the experimental data and procedures for the calculation of method bias, precision and accuracy are also included.

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.

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.

Evaluation of wipe sampling materials for lead in surface dust.

The suitability of several commercially available wipe sampling materials for the determination of lead in dust on solid surfaces was evaluated. Criteria for the selection of wipe materials appropriate for field use and subsequent laboratory analysis were identified. These included (a) uniform background lead levels in the materials (preferably < 5 micrograms); (b) ease of digestion in nitric acid/hydrogen peroxide or nitric acid/perchloric acid leachate; (c) > or = 80% recoveries of lead from standard reference material spikes; and (d) ease of use in the field. Other candidate wipe materials that were not examined in this study can be evaluated in a similar manner.

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.

An immuno-electron microscopic comparison of olfactory marker protein localization in the supranuclear regions of the rat olfactory epithelium and vomeronasal organ neuroepithelium.

Immuno-electron microscopy was used to examine olfactory marker protein (OMP) ultrastructural localization in the supranuclear regions of the rat olfactory epithelium (OE) and vomeronasal organ (VNO) neuroepithelium. In the OE, OMP immuno-reaction product was observed within the cytoplasm of olfactory chemoreceptor cell dendrites, vesicles and cilia. Reaction product was absent from olfactory microvillar cells and their unique microvillar projections. In the neuroepithelium of the VNO, immuno-reaction product was seen within the dendrites of the chemoreceptor cells, and in the bases of their attached microvilli; the remaining distal portions of these microvilli were unlabeled. These results demonstrate a difference in the distribution of OMP immunoreactivity over the surfaces of the rat OE and VNO. They also show that OMP immunoreactivity does not exist in the rat olfactory microvillar cells.

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.

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.

The effect of chronic cocaine abuse on human olfaction.

Cocaine has been used for many decades as both a stimulant and as a topical anesthetic/vasoconstrictor. Illicit "snorting" or freebase smoking has increased markedly in recent years. Decreased olfaction has been an often reported subjective complaint of cocaine abusers, but quantification of smell loss using sensitive psychophysical tests has not yet been done, leading to the present study. Eleven cocaine abusers were recruited from a drug treatment clinic. Olfaction was assessed using a butanol threshold test, the UPSIT, and a 7-item discrimination test. One patient tested anosmic, one had a mild discrimination problem, and one had a large septal perforation but was normosmic. From the present study, it appears that most cocaine abusers, even heavy users or those with intranasal damage, do not develop permanent olfactory dysfunction. It is not clear what factors may have resulted in complaints of olfactory loss in previous studies.

Congenital anosmia.

Seven patients with congenital anosmia underwent detailed chemosensory evaluation, followed by the performance of biopsies of the olfactory region. Olfactory epithelium was not found in any of the biopsy specimens. It appears therefore that patients with congenital anosmia lack any olfactory epithelium. Several possible explanations for this finding are discussed. The most attractive hypothesis is that the olfactory placode forms either normally or abnormally during development but later degenerates and is replaced with respiratory epithelium. Only one patient in our series had congenital anosmia in association with a syndrome (Kallmann's syndrome), indicating that congenital anosmia is found more often as an isolated symptom.

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.

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.

Electron microscopy of olfactory epithelia in two patients with anosmia.

Ultrastructural alterations were present in biopsy specimens of olfactory epithelia taken from two patients with anosmia. In both cases, the olfactory epithelia presented a disorganized appearance when viewed by transmission electron microscopy. The number of ciliated olfactory receptors was reduced; few olfactory vesicles were present at the epithelial surface. Where present, the olfactory vesicles usually lacked cilia. Since both patients had a history of head trauma, we speculate that the fila olfactoria may have been severed at the level of the cribriform plate. The histopathologic changes in the olfactory receptors that were revealed by electron microscopy may have resulted from the inability of regenerating axons to reach their normal site of synaptic contact--the second-order neurons (mitral cells) in the olfactory bulb of the brain.

A quantitative sampling device for use at hazardous waste sites.

A device to draw air through up to 10 direct reading indicator tubes simultaneously has been developed. The qualitative results obtained can be used to obtain a rapid preliminary classification of the unknown chemical substances at spill scenes or at hazardous waste sites, and to devise protocols for laboratory sample analysis.