Differential aspects of consultation-liaison psychiatry in a Saudi hospital. I: referral pattern and clinical indices.

Consultation-liaison psychiatry has emerged as an important sub-specialty in the general hospital setting during recent years as a result of psychiatric acute wards moving into these hospitals. This has inspired the need for better structured research to establish its relevance and effectiveness. We, therefore, carried out a prospective cohort study at King Fahad General Hospital. We report the interaction of sociodemographic, clinical and diagnostic factors, time lag of referral and diagnostic ability of referring physicians. A total of 206 patients were referred over a period of 6 months. Sensitivity and specificity of the diagnostic skills of the referring doctors were found to be generally poor, particularly for anxiety.

Differential aspects of consultation-liaison psychiatry in a Saudi hospital. II: knowledge and attitudes of physicians and patients.

To assess the attitude and knowledge of physicians and patients towards psychiatry, we asked 115 referring doctors and 188 referred patients to complete questionnaires. We examined the results along with the referral rates to try to identify factors that may affect a consultation-liaison psychiatry service. Generally, knowledge was poor and attitudes towards psychiatry negative in both groups. This negatively influenced the referral rates and reflected the lack of integration of psychiatry and medicine at the training level. This is an indication that psychiatrists need to work in collaboration with hospital doctors to integrate psychiatry into medicine at all levels and emphasizes the priority of education of hospital staff, patients and the community in consultation-liaison psychiatry.

Characterization of cytokeratin patterns in the developing human tongue.

The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well documented in human. Cytokeratin distribution in developing oral mucosa has not yet been described. The aim of this study was to identify the expression of CK in human fetal tongue (week 10 to week 23) and to correlate the results with morphological maturation. Simple epithelial CK are expressed in all cell layers during the early stages, essentially in peridermal cells. From the 14th week, CK 18 is present only in the taste buds, making this polypeptide a reliable marker for this sensory organ. CK 4 and 13 are expressed from the 10th to the 23rd week by both ventral and dorsal lingual epithelia. Terminal differentiation keratins (CK 1, 2 and 10-11) can only be detected immunohistochemically at the 14th week in some cells on the external surface of some papillae. The number of these papillae and positive cells increase at the 19th and 23rd weeks. The terminal differentiation markers are expressed several weeks earlier than the formation of a well-distinguished keratinized layer.

Chemically separated connective tissue grafts: clinical application and histological evaluation.

Subepithelial palatal connective tissue grafts, separated from the epithelium either chemically (n = 5) or surgically (n = 2) were inserted in patients presenting with gingival recession. Biopsies at the grafted tissue and a portion of non-keratinized mucosa were taken 12 months later. Histology showed keratinization of the newly formed epithelium, and interestingly a deep projection of epithelium into the connective tissue in almost all biopsies, sometimes with an enlargement and a cyst-like space. We conclude that chemical separation of epithelium and connective tissue is clinically feasible for connective tissue grafts and that the subepithelial connective tissue grafting technique should be modified to avoid this projection of epithelium.

Cytokeratin patterns of human oral mucosae in histiotypic culture.

In a three-dimensional culture model, oral epithelial differentiation was investigated ultrastructurally and biochemically for cytokeratin expression. Epithelia from the hard palate, gingiva and alveolar mucosa grown on freely floating collagen lattices populated with fibroblasts from homotypic origins, and fed with medium containing 10% delipidized fetal calf serum for 21 days before analysis, stratified and differentiated to basal cuboidal cells, polyhydral spinous cells and elongated superficial cells. The epithelium of palatal origin had non-nucleated superficial cells resembling orthokeratinized cells. The upper spinous cells had keratohyalin-like granules. The corresponding cells of gingival and alveolar mucosal origins retained their nuclei and had smaller numbers of keratohyalin-like granules. Basal cell keratins (CK 5 and 14) and those of hyperproliferation (CK 6 and 16) were consistently found in all epithelia. Furthermore, simple epithelial keratins (CK 18 and 19) were variably expressed by cells from different oral origins. In epithelial cells from the alveolar mucosa, CK 13 and 19 formed major bands, which correlates with their expression in vivo. In contrast, these polypeptides were either absent or formed minor bands in extracts of gingival and hard palatal cells. Although in small quantities, keratins of terminal differentiation (CK 1, 2, 10 and 11) were detected in gels prepared from palatal epithelia. This expression correlates with the higher morphological differentiation of these cells in this model. The model is of interest for studies of epithelial differentiation, as the differentiation markers of keratinized epithelia (CK 1 and 10) were expressed by cells from palatal origin, and those of non-keratinized epithelia (CK 4, 13 and 19) were prominent in cells from alveolar mucosal origin.

A comparative biochemical and immunological analysis of cytokeratin patterns in the oral epithelium of the miniature pig and man.

In man, cytokeratin constitutes a family of 19 polypeptides that show different but distinct distribution patterns in the various epithelia. Changes in these patterns may occur during epithelial development and differentiation. The cytokeratin patterns in the oral mucosa of the miniature pig, an animal used in studies of wound healing, were investigated. Surgical biopsies were obtained from the gingiva, hard palate and alveolar mucosa of both man and pig. The cytokeratins were analysed by immunofluorescence, two-dimensional gel electrophoresis and by immunoblotting. Nine monoclonal antibodies were used to identify the different cytokeratin polypeptides in cryostat sections. Two-dimensional gel electrophoresis showed that pig oral mucosa contains at least 10 different polypeptides, five of the acidic type I and five of the basic type II cytokeratins. These were different from the human cytokeratin polypeptides and accordingly were designated P1-P10, according to their molecular weight and isoelectric mobility. Their molecular weight varied between 48 and 69 kdalton and the pHi varied between 5 and 7.3. Immunoblotting showed the monoclonal antibody Ks 13.1 (anticytokeratins Nos 13 and 14) to cross-react with the pig polypeptides P10 and P8. Immunolocalization showed that all the antibodies cross-reacted with the pig tissue except Ks 19.1 (anticytokeratin No. 19). It was possible to differentiate between pig alveolar mucosa, which expressed only P3, P4, P5, P8 and P10, and the gingival and hard palatal mucosae, which expressed all 10 polypeptides except P5. This distinction was made by antibody 6B10 (anticytokeratin No. 4), which reacted only with alveolar mucosa; antibody Ks 13.1, which strongly reacted with uncornified mucosa but weakly with cornified mucosa (gingiva and palate); and any of RKSE60, Kk 8.60 or EE21.6 (anticytokeratin No. 10, anticytokeratins Nos 10 and 11 and anticytokeratins Nos 1, 2, 10 and 11, respectively), which reacted strongly with cornified mucosa but weakly, if at all, with uncornified mucosa. These findings provide a baseline for studies on epithelial differentiation in the miniature pig such as in wound healing.

Cytokeratin profiles in oral epithelial: a review and a new classification.

This article proposes a classification of oral epithelial and summarizes recent literature of cytokeratin expression in the oral cavity. The oral epithelial are subdivided into two major groups: superficial and deep epithelia. Epithelial lining the oral cavity, i.e., superficial, are essentially stratified squamous epithelia, with the exception of taste buds. The epithelium covering the dorsal tongue is a combination of keratinized and non-keratinized epithelia. Deep epithelia are of two kinds, odontogenic and glandular epithelia. This study provides a classification of the cytokeratins expressed in the oral cavity in healthy and pathological situations based on published data and our own studies. The profiles of these polypeptides in different oral epithelia should provide information that may be used in various disciplines of oral medicine.

In situ hybridization study of cytokeratin 4, 13, 16 and 19 mRNAs in human developing junctional epithelium.

Cytokeratins (CKs) are now considered to be reliable markers for following the development and differentiation of epithelial tissue. We have investigated the pathway of differentiation in human developing junctional epithelium using monoclonal antibodies and two-dimensional gel electrophoresis of microdissected tissue to identify CK 19, CK 16, CK 14, CK 13, CK 6, CK 5, CK 4 in the junctional epithelium (JE) over partially erupted human teeth. The CK profile was similar to that of developing oral epithelia, suggesting that the junctional epithelium in teeth during eruption is of odontogenic origin. The present study used in situ hybridization to determine the distribution of the mRNAs of CKs 19, 16, 13 and 4 in human developing junctional epithelium and to examine the correlation between mRNAs and their encoded proteins. CK 19 mRNA was abundant in the basal cell layers of the primary junctional epithelium (PJE) but less concentrated in the suprabasal layers. CK16, 13 and 4 mRNAs were abundant in the basal cell layers of the PJE. The parabasal cell layers reacted intensely to the cRNA probe complementary to CK16 mRNA, as were the reactions in the suprabasal cell layers of the PJE for the CK 13 and 4 probes. Our results demonstrate that the PJE express the genes encoding for CKs 16 and 4 that have been revealed previously only by electrophoresis. They therefore confirm that the PJE is a well-differentiated stratified epithelium with a complex unique phenotype that produces CKs specific for basal cells (CK 19), CKs associated with hyperproliferation (CK 16), and finally those associated with stratification (CKs 4 and 13). Only synthesis of CK 19 protein and mRNA are strictly parallel. CKs 4 and 13 mRNAs are present in basal and suprasal cells, while their encoded proteins were not, except for CK 13 in suprabasal cell layers of PJE, where the amount of its mRNAs was coincident with the expression of the protein.

Cytokeratin profile of the junctional epithelium in partially erupted teeth.

This study uses cytokeratins (CK) as markers to investigate the phenotype of the junctional epithelium (JE) in partially erupted human teeth. The gingival samples, which were clinically healthy, were carefully dissected from the teeth. Cryostat sections were cut for histological staining, immunofluorescence microscopy and gel electrophoresis. Cytokeratins were extracted after microdissection. The basal and suprabasal epithelial cell markers, cytokeratins 4, 5, 13, 14 and 19 were detected with specific monoclonal antibodies. They showed that the junctional epithelium in erupting teeth has a complex topography. The cytokeratin immunohistochemical profile distinguished between the primary junctional epithelium (CK 5, 14 and 19 in basal and suprabasal cells and CK 13 faintly stained throughout the suprabasal layers) and the adjacent epithelium that had the same cytokeratin profile as the sulcular epithelium (CK 5, 14 and 19 in basal cells and CK 4 and 13 intensively stained in the suprabasal cells). Extraction, two-dimensional electrophoresis and western blotting showed that this transitional JE during eruption also contained CK 6, 16 and perhaps CK 4. Thus, the JE in erupting teeth shows patterns of CK distribution that are very similar to that of developing oral epithelia.

Changes in cytokeratin expression during the development of the human oral mucosa.

The changes in cytokeratin expression by the developing oral mucosa of 10 to 23-week-old human fetuses were studied by indirect immunofluorescence using a panel of 15 monoclonal antibodies. The lining and masticatory mucosae were incompletely differentiated in 10-wk fetuses, since they expressed identical patterns of cytokeratins (CK 4, 5, 8, 13, 18, 19 and probably CK 14, 16, 17) very similar to that of adult alveolar mucosa. The main difference was the presence of cytokeratins 8, 18 and 19 in embryonic tissues. Cytokeratins 1, 2, 10 and 11 began to appear in gingival and hard palate epithelium from wk 11, predicting the differentiation of the masticatory mucosa by wk 16. The patterns of cytokeratin expression in the 23-wk fetus in the lining and masticatory mucosae appear to be different. In lining mucosa, the only difference from the 10th wk is a decrease in cytokeratins 8, 18 and 19, whereas the pattern of cytokeratin expression in masticatory mucosa (CK 1, 2, 4, 5, 8, 10, 11, 13, 18, 19 and probably CK 14, 16 and 17) is now very near that of adult gingiva. This pattern appears, as in the adult, to be similar to that of the epidermis in the same period.

Cytokeratin expression in human tongue epithelium.

The epithelium of the human tongue shows diverse morphological variations from one site to another and even within the epithelium of the same papilla. This complexity has led to confusion regarding tongue epithelium as being orthokeratinized, parakeratinized, or nonkeratinized. Cytokeratins have been shown to characterize different epithelia. The present paper describes cytokeratin expression by adult tongue epithelia and relates their distribution to morphology. Six healthy human tongue specimens were obtained after plastic surgery and cytokeratin expression was investigated immunohistochemically, using a panel of 15 antibodies for cytoskeletal proteins, and biochemically using two-dimensional gel electrophoresis. The results showed that the ventral and lateral surfaces of the tongue are related to the nonkeratinizing stratified squamous epithelia, esophageal type, whereas the dorsal surface showed mixed expression of cytokeratins. In the tip of filiform and on the surface of fungiform papillae, cytokeratins of terminal differentiation are expressed as skin type; and in the rest of the papillae as well as in interpapillary areas, the epithelium expresses esophageal type cytokeratins. Certain simple epithelial cytokeratins were found in taste buds. Cytokeratin 19 was also detected in the basal cell layer of all esophageal type epithelia in the tongue. The present results provide basis for studies on the biological events in epithelial differentiation during development and in pathology.

Evolution of cytokeratin expression in developing human tooth germ.

Cytokeratin expression by the developing human enamel organ between the 10th and the 23rd gestational week was studied by indirect immunofluorescence microscopy technique using a panel of 15 monoclonal antibodies. The results showed that five antibodies (RKSE 60, Kk 8-60, EE 21-6, 6B10 and 1 C-7) were never reactive, that five antibodies (RCK 102, 42.39.13.1, Ks 19 and Pan 1-8) were always positive and that five antibodies (KB 37, RPN 11-62, Ks 13.1, Ks 8-12 and Ks 18.174) obtained or increased their positivity between weeks 12 and 13. It was concluded that a switch in cytokeratin expression occurred around the 12th-13th weeks. No further important change could be noticed after this period. So it is suggested that final cell differentiation was initiated at weeks 12-13.

A switch in cytokeratin expression and intermediate filament organization associated with epithelial stratification.

Low density gingival epithelial cells were cultured on the side of glass slides facing rat's tail collagen lattices. Under these conditions and in the presence of physiological level of calcium, colony formation was enhanced and stratification was slowed down. The strong attachment of the cells to glass slides permitted immunocytochemical examination of cytokeratin (CK) expression and their organization within individual cells during the different stages of epithelial maturation. The present results showed that during the stage of cell migration and colony formation, the cells express the same set of cytokeratins (basal cell marker 14, simple epithelial markers 8, 18 and 19, and marker of hyperproliferation 16) which forms a well-defined network of organized filaments. At the stratification stage, the filament network became dense by the additional expression of the markers of differentiation in non-keratinized stratified epithelia (CK 4 and 13). These appeared once individual cells started to overlap the basal cells, a period during which the cell-temporarily changed morphology. Whilst the suprabasal cells exhibited dense filament network labelled for CK 4 and 13, the density of labelled filaments for CK 14, 8 and 18 was much lower, indicating that these cells contained newly-formed filaments lacking the basal and simple epithelial keratins. The simple epithelial cytokeratins became weakly labelled in older cultures. The uncoupling of paired expression of cytokeratins 4 and 13 was observed in non-colony forming aged cells. This provides an example of altered program of cytokeratin expression during epithelial maturation.

[Cytokeratins, markers of epithelial cell differentiation: expression in normal epithelia]. / Les cytokératines, marqueurs de la différenciation des cellules épithéliales: expression dans les épithéliums sains.

Intermediate filaments, the most stable of cytoskeleton components, are extremely diverse and usually correlate with the histological subtype since in nearly all cell types a single type of intermediate filament (IF) is found. The cytokeratins, which are specific of epithelia, are the largest and most diverse class of intermediate filaments. Twenty different cytokeratin polypeptides have been identified in humans and separated on the basis of isoelectrical pH and apparent molecular weight using two-dimensional electrophoresis. These data have been used to establish a cytokeratin catalogue which currently serves as a reference [43, 48]. The number of cytokeratin polypeptides expressed ranges from 2 to 5 for each epithelial cell and from 2 to 10 for each epithelium and even of each cell layer within a given epithelium. A broad spectrum of anticytokeratin antibodies with subgroup or single polypeptide specificity is currently available. The distribution of cytokeratins in normal epithelia is reviewed herein and commercially available anti-cytokeratin antibodies are listed.

[Expression of cytokeratins during embryogenesis and in pathologic epithelia]. / Expression des cytokératines au cours de l'embryogénèse et dans les épithéliums pathologiques.

Epithelial cell intermediate filaments, or cytokeratins, are excellent markers for cell differentiation. During embryogenesis, cytokeratins specific of a stage of differentiation step always become detectable before corresponding morphologic changes: for instance, cytokeratins 5 and 14 are found around the eight week, shortly before stratification of the epithelium occurs, and cytokeratins 1 and 10 are produced before morphologic evidence of keratinization becomes detectable. Among potential diagnostic applications, analysis of cytokeratin patterns of epidermal cells desquamated in the amniotic fluid may provide earlier and less invasive diagnosis than fetoscopic biopsies. Similarly, a review of cytokeratins expressed in a variety of epithelial diseases (involving the epidermis, digestive tract, respiratory tract, urogenital tract, or breast) demonstrated persistence of the original tissue pattern in some instances (this was the case for the majority of simple epithelia) but not in others (complex epithelia). This suggests that cytokeratins may prove valuable as markers for specific tumor stages or types and may provide earlier information than morphologic studies.

Changes in cytokeratin expression in gingiva during inflammation.

Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The purpose of this study was to describe the alterations of cytokeratin pattern and topographical distribution of individual cytokeratins in inflamed gingiva. Five healthy and 15 inflammatory samples of human gingiva were studied. From each biopsy, cryostat sections allowed histological staining, immunofluorescence microscopy using a battery of monoclonal antibodies to cytokeratins, and gel electrophoresis. The results show marked differences in cytokeratin expression by healthy epithelia as compared with inflamed gingiva: in suprabasal cell layers there were reductions or disappearance of cytokeratins 1, 2 and 10, 11--specific for terminal differentiation--and increased expression of cytokeratins 4 and 13, as well as--in basal and parabasal cell layers--expression of cytokeratin 19. These alterations might represent an adaptation of involved epithelia to the alterations brought about by the inflammatory process.

Differential aspects of consultation-liaison psychiatry in a Saudi hospital. II: knowledge and attitudes of physicians and patients

To assess the attitude and knowledge of physicians and patients towards psychiatry, we asked 115 referring doctors and 188 referred patients to complete questionnaires. We examined the results along with the referral rates to try to identify factors that may affect a consultation-liaison psychiatry service. Generally, knowledge was poor and attitudes towards psychiatry negative in both groups. This negatively influenced the referral rates and reflected the lack of integration of psychiatry and medicine at the training level. This is an indication that psychiatrists need to work in collaboration with hospital doctors to integrate psychiatry into medicine at all levels and emphasizes the priority of education of hospital staff, patients and the community in consultation-liaison psychiatry