Central laboratory and point-of-care cardiac marker testing capacity of tertiary hospitals in Nigeria – a multicenter study

BackgroundCardiovascular diseases are major contributors to morbidity and mortality. It is generally recognized that cardiac markers are of particular benefit in the evaluation of patients with suspected Acute Coronary Syndrome (ACS). Tertiary hospitals, mainly teaching hospitals, are expected to be optimally equipped to offer these services. The study therefore aimed at determining the central laboratory and point-of-care cardiac marker testing capacity of tertiary hospitals in Nigeria.MethodA cross-sectional survey was carried out in government-owned tertiary hospitals in Nigeria. Data were collected using semi-structured self-administered questionnaires, and analyzed using Stata version 13 (Stata Corp., USA).ResultsA total of 34 hospitals participated in the study. The mean (SD) age of respondents was 43.68 (5.2) years. A total of 19 (55.88%) hospitals were found to have a functional cardiac marker testing facility, either in the form of point-of-care, central laboratory testing or both. Of those without a facility, lack of funds to procure equipment was the major reason given. In hospitals with a testing facility, most testing devices were located in the Central laboratory.ConclusionCardiac marker testing capacity of tertiary hospitals in Nigeria, both in the form of point-of-care and central laboratory testing, was found to be barely adequate. Improvement is needed in this area for better diagnosis and evaluation of patients who need the tests.     

The effect of a change from conventional cardiac enzymes to troponin I on overall hospital costs in patients with suspected myocardial infarction

A random sample of patients presenting to this hospital in 1996 and 2000 with chest pain was assessed retrospectively with respect to patient bed stay and associated costs. The laboratory testing protocol had been changed from traditional cardiac markers AST, CK and CKMB, to troponin I, in the intervening period. The average bed stay for patients with chest pain of non-AMI origin was reduced by 2 days, as a result of the change in testing protocol. As ward costs contribute 49% of total cost of treatment, this resulted in decreased cost per patient, and more efficient use of hospital beds.     

Evaluation of the i-STAT Portable Clinical Analyzer for point-of-care blood testing in the intensive care units of a university children's hospital

We evaluated the analytical performance of the i-STAT Portable Clinical Analyzer (PCA), a point-of-care testing system consisting of a hand-held analyzer and single-use cartridges that measure different panels of electrolytes, metabolites, blood gases, and hematocrit in 65-100 microl of blood. Our objective was to determine whether PCA measurements at the bedside of patients in the neonatal and pediatric intensive care units of the MUSC Children's Hospital would be as reliable as those performed by the clinical laboratory's primary methods (Radiometer ABL 725 blood gas analyzer; Vitros 750 chemistry analyzer; and Coulter STKS hematology analyzer). Four cartridge types: (a) EC8+ (sodium; potassium; chloride; urea; glucose; pH; blood gases [PO2; pCO2]), (b) EC6+ (sodium; potassium; ionized calcium; glucose; hematocrit; pH), (c) G3+ (pH; PO2; pCO2), and (d) creatinine, were assessed for reproducibility, linearity, and method comparisons using aqueous samples, blood samples supplemented with several analytes, and -225 blood samples from patients. Reproducibility (CV) was good (< 2%) for electrolytes, glucose, urea, and pH, satisfactory (< 6.5%) for blood gases and creatinine, but poor (21%) for hematocrit. Linearity concentrations spanning the clinically relevant ranges were verified for all analytes. Method comparison studies with samples separated into 2 subgroups by patient age (> or < 3 mo) showed that agreement between the PCA and the primary methods was clinically acceptable. After the PCA was implemented for clinical testing, the observation of discrepant results of creatinine concentrations in neonatal blood samples that would have affected clinical management led to a second creatinine comparison study (59 additional samples) and to our eventual discontinuation of the PCA creatinine assay. This problem notwithstanding, the successful implementation of the PCA is attributed to careful analytical evaluations and ongoing communication with the clinical staff.     

Paternity testing: analysis of six blood groups and HLA markers, with particular reference to comparison of races

Blood groups (ABO, Rh, MNSs, Kell, Duffy, and Kidd) and HLA markers were tested in cases involving 563 children of disputed parentage. In 149 (26.5%) cases, the accused men were excluded as the biologic fathers of the children in question. One hundred forty of the 149 exclusions were direct exclusions. Five exclusions were based on red blood cell data alone, i.e., HLA was non-exclusionary. Of the remaining 414 cases in which the alleged father could not be excluded as the biologic father, in 361 (87.2%) instances, the plausibility of paternity ws 95% or greater, and in 385 (93.0%) instances the comparison of men value was 20 or greater. Caucasians, blacks, and men of other races were involved in 367 (65.1%), 185 (33%), and 11 (1.9%) cases, respectively. No significant difference among races was observed in the rate of exclusion of accused men. However, of the non-excluded men, in a significantly greater proportion of black men than white men, the plausibility of paternity was below 95%. The difference was probably due to lower polymorphism of the markers tested in blacks than in whites. It is suggested that tests for additional polymorphic genes be directed towards the 12-15% of the nonexclusionary cases with plausibility of paternity values below 95%.     

Multicenter evaluation of h-FABP semi-quantitative assay (Cardio Detect) in central laboratory: the point in acute myocardial infarction diagnosis

The diagnostic performance of heart-Fatty Acid Binding Protein (h-FABP) (semi-quantitative CardioDetect test) and cardiac troponin I (TnIc) blood assays were compared in one hundred patients presenting with suspicion of acute coronary syndrome. Final patient diagnosis was "acute myocardial infarction" in 36 cases, "non ST myocardial infarction" in 25 cases and "non ischemic pathologies" in 39 cases. h-FABP results were positive in 26 patients, negative in 57 patients and ambiguous in 17 patients, the latter corresponding to the final diagnosis of "acute myocardial infarction" in 5 cases, "non ST myocardial infarction" in 2 cases and "non ischemic pathologies " in 10 cases. At admission, h-FABP and TnIc exhibiteda sensitivity of 54% an 66%, respectively and a specificity of 86% and 95%, respectively. Positive and negative predictive values were 81% and 64% for h-FABP, respectively and 92% and 75% for cTnI, respectively. h-FABP and cTnI demonstrated a similar diagnostic efficiency if admission delay is less than 4 hours after onset of chest pain (area under ROC curve TnIc = 0.767 +/- 0.091 ; area under ROC curve h-FABP = 0.622 +/- 0.109 ; p = 0.144). On the contrary, cTnI assay demonstrated a better efficiency than h-FABP (p< 0.005) for patients admitted in a delay of 4 to 12 hours after the onset of chest pain. If chosen cTnI cut-off corresponded to the recent consensus definition used for monitoring acute coronary syndrome patients, h-FABP semi-quantitative assay realized within central laboratory did not demonstrated a better diagnostic efficiency than cTnI.     

Troponin I, laboratory issues, and clinical outcomes in a district general hospital: crossover study with "traditional" markers of myocardial infarction in a total of 1990 patients

AIMS: Review of the clinical outcomes and practical issues of replacing traditional cardiac enzymes with troponin I (cTnI) in a district general hospital. METHODS: Crossover study of three sequential three month stages during which serial cardiac enzymes were replaced with a single cTnI measurement available at three set times within 24 hours for the duration of the second three month stage. The study was carried out in a 630 bed district general hospital with 1990 admissions of suspected cardiac ischaemia over the study period as a whole. Account was taken of seasonal factors. RESULTS: The introduction of troponin was associated with 8.5% more patients with non-ischaemic heart disease (IHD) being discharged on the day after admission, saving approximately 107 bed days each year. Approximately 50% more patients were diagnosed with myocardial infarction during the cTnI stage. There was no increase in readmission within one month or early death with cTnI. Approximately 3% false positive and 1.5% false negative cTnI results were recorded. All false positive cTnI results were coding errors or attributable to known assay interference effects. All false negatives were potentially explained by sample timing factors. The lack of standardisation in troponin assay services impacts clinically. CONCLUSION: Younger patients without IHD were discharged earlier during the cTnI stage in apparent safety. Blood sample timing needs to be verified when cTnI is used as an adjunct to early discharge. There were no unexplained false positives or negatives. Standardisation related issues arose.     

Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston marathon

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P < .001) and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded.     

Arterial blood gases,muscle fiber diameter and intercapillary distance in cardiac hypertrophy of rats with an old myocardial infarction

In rats with a myocardial infarction due to ligation of the left coronary artery a marked right ventricular hypertrophy developed after 41/2 weeks. At this time no difference against control animals was observed in arterial , , pH, ideal alveolar , and alveolar-arterial O₂ pressure difference, as measured in unanesthetized animals at normoxia. In histological sections of the heart stained by PAS reaction capillaries and muscle fibers were counted, and the mean intercapillary distance and muscle fiber diameter were estimated. In the right ventricle of the rats with myocardial infarction both increased when compared with control animals or with sham-operated rats. Fibercapillary ratio was the same in all three groups. Similar results were obtained in the remaining undamaged tissue of the left ventricle of rats with a myocardial infarction when compared with the left ventricle of control or sham-operated rats. Findings concerning intercapillary distance suggest that also in the myocardium which remains intact during the development of the infarction and later hypertrophies, tissue oxygen transport might be impaired, particularly during a stress situation. Results in the right ventricle of rats with myocardial infarction show an opposite trend against rats exposed chronically to simulated high altitude, where in the hypertrophied right ventricle a shorter intercapillary distance occurs and therefore an improvement of tissue oxygen transport might be expected.Dedicated to Professor Dr. Adolf Faller, University of Fribourg, Switzerland, on his 65th birthdayPresented in part at the IXth World Conference of the European Society for Microcirculation, Antwerp, July 5–9, 1976     

Effectiveness of blood irradiation using a helium-neon laser in the acute period of myocardial infarction

The efficacy of endovascular irradiation of the blood with He-Ne laser by the method developed by the authors was examined in 295 patients with primary acute transmural myocardial infarction. Laser therapy was conducive to effective alleviation of the pain syndrome and prevention of anginous status. Twenty-four-hour Holter monitoring, carried out before and after irradiation, has detected high antiarrhythmic activity in respect of complex ventricular arrhythmias and a preventive possibility of fibrillations. Studies of precardial ECG parameters and measurements of the blood enzymic activities (creatine phosphokinase and MB creatine phosphokinase) have shown that irradiation carried out within the first hours of myocardial infarction is conducive to limitation of the infarction area, i.e. that endovascular laser therapy is a highly effective and pathogenetic method for acute myocardial infarction treatment.     

人脐血单个核细胞多次静脉移植家兔急性心肌梗死后的胶原重构

背景：以往干细胞移植治疗心肌梗死的研究,均为单次经静脉或冠脉注射移植。 目的：进一步验证人脐血单个核细胞多次静脉移植对家兔急性心肌梗死胶原重构及心功能影响。 方法：取家兔45只结扎冠脉左前降支制备急性心肌梗死模型,随机分为3组,①多次移植组：造模后7,9,11,13 d经耳缘静脉注入BrdU标记人脐血单个核细胞生理盐水。②单次移植组：造模后7 d注入BrdU标记人脐血单个核细胞生理盐水,9,11,13 d注入生理盐水。③心梗对照组：仅注入生理盐水。另取家兔5只为假手术组。 结果与结论：与对照组相比,两移植组心功能左室短轴缩短率、左室射血分数明显升高(P < 0.05);且多次移植组改善效果优于单次移植组(P < 0.05);免疫组织化学显示两移植组造模后2,4周心梗周边区均存在BrdU阳性细胞,但多次移植组BrdU阳性细胞计数多于单次移植组;改良Masson’s染色显示与假手术组比较,对照组梗死区及非梗死区胶原密度显著增加,梗死区域胶原纤维部分融合,排列较紊乱,心肌基本组织结构破坏;与对照组比较,两移植组造模后2,4周梗死周边区域心肌细胞间胶原含量、胶原纤维明显减少,胶原纤维排列较为有序;与单次细胞移植组比较,多次细胞移植组进一步改善。提示多次静脉移植脐血单个核细胞改善急性心肌梗死心功能、阻抑心肌胶原纤维重构疗效优于单次静脉移植。     

Evaluation and implementation of the gel test for indirect antiglobulin testing in a community hospital laboratory.

BACKGROUND: The gel test, developed by Lapierre in 1984, was designed to standardize antiglobulin testing while improving sensitivity and specificity of the method. PRINCIPLE: Anti-human serum immunoglobulin G (IgG) mixed with Sephadex G100 (gel phase) in a microtube traps red cell-IgG agglutination complexes during migration through the gel in a centrifugation step. Agglutination complexes are visibly detectable at various levels in the microtube as an inverse function of antibody coated on red cells. Unsensitized red cells form a cell pellet at the base of the microtube. OBJECTIVE: To determine if indirect anti-human globulin testing could be standardized and simplified by replacing the tube test with the gel test without compromising quality or increasing costs. SETTING: A medium-sized community hospital. RESULTS: In a blinded retrospective study, we used patient sera (n = 40), which included 10 positive specimens containing 18 known antibodies. Sixteen antibodies were detected and identified with the tube method (1 anti-D and 1 anti-C not detected). By the gel test, 18 antibodies were detected and identified. All negative samples showed 100% concordance. Favorable results were obtained in a nonblinded prospective correlation study (n = 121). Our technologists found the gel test easier to read and more reproducible and reliable than the tube method; they also found increased sensitivity for detecting weakly reacting antibodies. We successfully introduced the gel test into our laboratory as the standard method for indirect antiglobulin testing. Following implementation, improved personnel management was achieved. CONCLUSIONS: The gel test is a reliable and advantageous method and is appropriate for routine use for detection and identification of alloantibodies in a community hospital transfusion service laboratory.     

Evaluation of two commercially available test methods to determine the feasibility of testing for respiratory syncytial virus in a community hospital laboratory

The feasibility of performing respiratory syncytial virus (RSV) testing in a community hospital laboratory was assessed. The Abbott RSV EIA Kit, an enzyme immunoassay (EIA), and the Ortho Respiratory Syncytial Virus Identification Reagent, a direct fluorescent antibody (DFA) technique, were evaluated in terms of technologist time, result time, cost, and agreement of results. There was little difference in the amount of technologist time required for either method. The DFA technique was shown to be much less expensive than the EIA method and also required at least 50% less time to generate a final result. When compared with an indirect fluorescent antibody technique, the EIA technique was more sensitive (87%) than the DFA method (81%). Both methods showed 100% specificity. Based on the findings of this study, the DFA technique was determined to be the more feasible method for a community hospital laboratory to use for the rapid detection of RSV.     

Evaluation of the membrane attack complex of complement for the detection of a recent myocardial infarction in man

The diagnosis of an acute myocardial infarction (MI) can be cumbersome for pathologists. Even with a positive nitroblue tetrazolium (NBT) reaction, haematoxylin and eosin (H&E) evaluation of the myocardial tissue can remain inconclusive. Early signs presumed diagnostic for myocardial infarction, such as hypereosinophilia, waviness, and contraction band necrosis, have to be considered non-specific and are probably reversible signs of ischaemia. Several studies implicate the complement system, and especially complement factor C9, as part of the membrane attack factor (MAC), in cardiomyocyte damage during MI. In a post-mortem study on well-documented cardiological autopsies, we evaluated the use of complement factor C9 immunostaining as a marker for the detection of very recent MI. Forty-three tissue samples from 40 patients were obtained from the left ventricular free wall only, a region that can be specifically attributed to one corresponding coronary artery. As some patients presented with MIs of various stages in that perfusion area, in total 57 observations were possible. C9 immunostaining specifically detected irreversibly damaged (=infarcted) cardiomyocytes, as is implied by the lytic activity of C9/MAC binding to cell membranes. Most interesting was the group of clinically suspected, NBT-positive MIs resulting from very recent myocardial ischaemia. In this population, where H&E evaluation by (cardio-) experienced pathologists was not conclusive, C9 immunostaining clearly pointed towards myocardial infarction in 47% of the cases. In conclusion, C9 immunostaining, routinely practicable in the pathology laboratory, has an additional value in discriminating between reversible ischaemia and infarcted cardiomyocytes in very early MIs.     

Simultaneous assessment of left-ventricular infarction size, function and tissue viability in a murine model of myocardial infarction by cardiac manganese-enhanced magnetic resonance imaging (MEMRI)

Owing to its signal-enhancing characteristics in viable well-perfused tissue, divalent manganese (Mn2+) has been used as a myocardial imaging contrast agent. Because Mn2+ can enter excitable cells through the voltage-gated L-type calcium channels, manganese-enhanced MRI (MEMRI) has been used to determine the viability and the inotropic state of the heart. In this study, we examined the correlation between left ventricular infarction zone as assessed by cardiac MEMRI and function in mice with permanent coronary artery occlusion. At an Mn2+ infusion dose of 1.72+/-0.47 nmol/min/g body weight, the steady-state signal intensity (SI) enhancement 20-26 min post-Mn2+ infusion of the normal septum and left-ventricular wall during diastole was 128.2+/-14.4 and 127.9+/-26.5%, respectively, whereas the infarction zone was 56.0+/-7.1%. During systole, the SI enhancement was 144.6+/-33.0, 116.0+/-18.7 and 48.3+/-20.0% for the normal septum, left-ventricular wall and infarction zone, respectively. A good correlation was obtained between the MEMRI determined infarction volume and conventional histological TTC staining (r = 0.9582, p<0.01). There was also a strong negative correlation between MEMRI determined infarction percentage (compared with whole left ventricle) and ejection fraction (r = -0.94, p<0.05). These data suggest that the Mn2+ concentration at steady state in the heart may reflect altered tissue viability in the infarcted tissue as well as surrounding region following myocardial infarction. In conclusion, in vivo cardiac MEMRI offers a manner in which functional, pathologic and viability data may be obtained simultaneously in myocardial tissue.     

Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve

BACKGROUND: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. METHODS: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. RESULTS: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of approximately 0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. CONCLUSIONS: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.     

Preliminary evaluation of a rapid, qualitative one step immunoassay of cardiac Troponin I in the acute myocardial infarction diagnosis

The cardiac Troponin I is considered the biochemical marker of election to detect acute myocardial infarction, a medical urgency that requires a rapid diagnosis. In this article, the diagnosis of this condition was studied qualitatively through an immunochromatographic assay of a single step detection of cardiac Troponin I elaborated in the laboratory comparing it with another, commercially available, qualitative immunochromatographic assay of detection of cardiac Troponin I, Cardiac STATUS TM. The plasmas of 76 patients with acute myocardial infarction and 50 plasmas obtained from healthy donors were evaluated retrospectively. The laboratory's immunoassay did not present cross reactivity with the skeletal isoform of Troponin I. This test detected 1 ng/mL or more of cardiac Troponin I in the form of a tertiary complex in plasma and it also recognized the free molecule. The clinical sensitivity of the immunoassay of the laboratory in patients with Q wave type acute myocardial infarction was 100% and for the commercial immunoassay was 85.7% in the period of 6 h to 24 h following the onset of chest pain. For this type of infarction, the signal was detected up to 148 h after the onset of symptoms and the clinical sensitivity oscillated between 84.2% and 90.9% for both assays. The clinical sensitivities of the two immunoassays were 70% in the case of patients with non-Q wave acute myocardial infarction. With healthy donor's samples, the clinical specificity of the immunochromatographic assay prepared in the laboratory was of 90.4% and for commercial immunoassay was 100%. The immunochromatographic immunoassays of a single step for the detection of cardiac Troponin I evaluated in this work, diagnosed in a quick and easy way, important myocardial cell death and to lesser extent smaller necrosis, in patients without concluding electrocardioghraphic signs and with the possibility of the occurrence of complications.     

Histological definition of the vomeronasal organ in humans and chimpanzees, with a comparison to other primates

The vomeronasal organ (VNO) is a chemosensory structure that has morphological indications of functionality in strepsirhine and New World primates examined to date. In these species, it is thought to mediate certain socio-sexual behaviors. The functionality and even existence of the VNO in Old World primates has been debated. Most modern texts state that the VNO is absent in Old World monkeys, apes, and humans. A recent study on the VNO in the chimpanzee (Smith et al., 2001b) challenged this notion, demonstrating the need for further comparative studies of primates. In particular, there is a need to establish how the human/chimpanzee VNO differs from that of other primates and even nonhomologous mucosal ducts. Histochemical and microscopic morphological characteristics of the VNO and nasopalatine duct (NPD) were examined in 51 peri- and postnatal primates, including humans, chimpanzees, five species of New World monkeys, and seven strepsirhine species. The nasal septum was removed from each primate and histologically processed for coronal sectioning. Selected anteroposterior intervals of the VNO were variously stained with alcian blue (AB)-periodic acid-Schiff (PAS), PAS only, Gomori trichrome, or hematoxylin-eosin procedures. All strepsirhine species had well developed VNOs, with a prominent neuroepithelium and vomeronasal cartilages that nearly surrounded the VNO. New World monkeys had variable amounts of neuroepithelia, whereas Pan troglodytes and Homo sapiens had no recognizable neuroepithelium or vomeronasal nerves (VNNs). Certain unidentified cell types of the human/chimpanzee VNO require further examination (immunohistochemical and electron microscopic). The VNOs of P. troglodytes, H. sapiens, and New World monkeys exhibited different histochemistry of mucins compared to strepsirhine species. The nasopalatine region showed great variation among species. It is a blind-ended pit in P. troglodytes, a glandular recess in H. sapiens, a mucous-producing duct in Otolemur crassicaudatus, and a stratified squamous passageway in all other species. This study also revealed remarkable morphological/histochemical variability in the VNO and nasopalatine regions among the primate species examined. The VNOs of humans and chimpanzees had some structural similarities to nonhomologous ciliated gland ducts seen in other primates. However, certain distinctions from the VNOs of other primates or nonhomologous epithelial structures characterize the human/chimpanzee VNO: 1) bilateral epithelial tubes; 2) a superiorly displaced position in the same plane as the paraseptal cartilages; 3) a homogeneous, pseudostratified columnar morphology with ciliated regions; and 4) mucous-producing structures in the epithelium itself.