[Acute abdomen and carcinoma of the glandula parotis].
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Biomedical subjects
Publications and source records attributed to G M Sprinzl.
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The combination of radiation and chemotherapy administered for patients undergoing therapy for advanced head and neck neoplasms leads to a significant rise in toxic side-effects. Oral mucositis remains one of the most distressing factors leading to pain, impairment of oral nutrition, local and systemic infection and often cessation of the oncological treatment. The local and systemic administration of recombinant growth factors has revealed a potential benefit in the treatment of oral mucositis. Clinical data concerning the topical use of granulocyte-macrophage colony-stimulating-factor (GM-CSF) in the prevention and therapy of mucositis in patients undergoing radiochemotherapy for advanced cancer of the head and neck are presented in this paper. A prospective, randomised, open parallel-grouped, single centre study at a university hospital was performed. 35 patients with stage III and IV carcinomas of the head and neck were included. Statistical analysis concerning the degree of oral mucositis, the perception of pain, the incidence of secondary infections and the change in haematological parameters revealed no superiority of GM-CSF in comparison to conventional mouthwash between the two groups of patients. As a result, and faced with the tremendous costs of the regular use of a recombinant cytokine, we ended the clinical trial after 35 patients. The topical administration of GM-CSF to treat oral mucositis as a result of radiochemotherapy in patients suffering from head and neck cancer cannot be recommended.
Dendritic cells (DC) are professional antigen-presenting cells whose primary function is the initiation of immune response. Based on the finding that the immune system usually fails to identify and kill cancer cells, DC have been recently used as vaccines for stimulation of tumour-specific immunity. This review focuses on pitfalls related to DC-based vaccination against solid tumours and on improvement of this immunotherapeutic approach for routine treatment of cancer disease.
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BACKGROUND: The morphological development of the human larynx during the first years of life has previously not been studied in detail and has mainly been described on a qualitative basis. This study seeks to provide detailed morphometric data on the regular anatomy of the vocal cords, the subglottic airway and the tracheal airway dimensions gained from plastinated whole organ serial sections of 43 infant larynges and to determine morphological changes with age. Such information may be useful for the understanding of pediatric airway disease or for laryngeal surgery in children. MATERIAL AND METHODS: The larynges of 43 children aged 1 to 60 months were plastinated. Whole organ serial sections were obtained by cutting the resulting specimen with a diamond band saw. Morphometry of whole-organ sections was accomplished using a high resolution, computer-based image analyzer. The total length of the glottis, length of the cartilaginous and ligamentous glottis, subglottic cartilaginous cross-section, subglottic airway and tracheal airway were determined for each specimen. RESULTS: The subglottic airway increases considerably in size during the first 2 years of life (from 13 to 28 mm2 in the means). Further growth seems to follow a linear mode. The relative proportion of the mucosal lining of the subglottic airway decreases likewise. While it occupies approximately 50% of the subglottic cartilaginous cross-section during the first two years of age, its relative proportion decreases to some 30 to 40% between age three to five. Other than in adults, and comparable to most mammals, the cartilaginous glottis accounts for 60 to 75% of the vocal folds' length in children under two years of age. The anterior ligamentous part of the glottis outsizes its posterior cartilaginous portion during the third year of life. CONCLUSION: This study supplies detailed morphometric data on the growth and structure of the human larynx during the first years of life that have not been available to date. Previous studies on the anatomical configuration of the infant larynx have focused on the the perinatal larynx, the prepuberal and puberal larynx, and the development of collagen fibres in the developing larynx. The human larynx has undergone significant evolutionary adaptations. Among them are the descent of the larynx, the capability of vocal fold adjustment in length, tension and shape, and the prominent configuration of the membranous part of the vocal folds as opposed to the cartilaginous part. The infant larynx is not just a miniature of the adult organ. It shows differences in its position relative to the vertebrate column, in the composition of cartilages and soft tissues, and in environmental adaptation. The present study is the first to supply detailed morphometric data on the growth and structure of the human larynx during the first five years of life and on the morphological changes of the larynx during this period. From these data it seems that some of the adaption of the human larynx as opposed to other vertebrates are not fully developed at birth, but undergo postnatal maturation. The relative proportions of the cartilaginous and membranous parts of the vocal folds clearly demonstrate this maturation process: While the posterior "respiratory" glottis accounts for some sixty to 75% of the total glottic length in newborns, its relative proportion decreases throughout the first years of life and finally equals the proportions of the adult larynx. Other than in adults, and in accordance with the literature, no sexual dimorphism of the larynx could be detected in this series of infant larynges. Morphometric data on the growth and structure of the human vocal folds and the subglottic airway during childhood are presented. Plastinated whole organ serial sections were used in the study to show the infant laryngeal morphology. The study provides quantitative anatomical data of clinical interest that light up the anatomy of the pediatric airways.
BACKGROUND AND OBJECTIVE: Patients with advanced head and neck cancer often suffer from malnutrition even before the start of therapy. Hence, the demand for nutritional support increases particularly before and during radiochemotherapy. Though nutritional therapy has been shown to substantially improve individual outcome, neither the criteria for patient candidacy nor the indications for therapeutic intervention have been established. We performed a retrospective analysis to determine the indications for nutritional support and < 0 evaluate the benefits of measures actually taken against malnutrition before and during radiochemotherapy as well as perioperatively. PATIENTS/METHODS: Data taken from a prospective study for the evaluation of oral mucositis during radiochemotherapy was analysed retrospectively. To calculate the indication for nutritional support, a nutritional scoring system (Hackl) was employed for the first time, which contained biochemical and anthropometric parameters as well as the period of starvation. The results were then compared to a nutritional support program implemented by the subjective examinations of the attending physician. RESULTS: Changes in body weight and body mass index (BMI) remained the most impressive parameters. Catabolic metabolism developed preoperatively and a significant loss of whole-body protein followed surgical therapy. Clinically, the results of the nutritional score correlated with the observation of malnutrition. Furthermore, our findings suggest that nutritional therapy was commonly delayed until late in the clinical course. CONCLUSION: The results indicate the necessity of objective and reproducible diagnosis and control of malnutrition. The scoring system used may provide a useful and yet simple tool for assessing individual indications for timely nutritional support.
OBJECTIVES: Hyperplastic lesions of the laryngeal mucosa can eventually develop into squamous cell carcinoma The relationship between dendritic cell infiltration of head and neck cancers and prognosis is well known. Surprisingly, data regarding dendritic cell infiltration in precancerous lesions are not available today. It was the purpose of our study to extend these observations and to investigate in more detail the density and distribution of dendritic cells in pre-cancerous lesions. STUDY DESIGN: Retrospective survey by immunohistochemistry. METHODS: For this study we investigated paraffin-embedded tissue sections of 41 specimens. Histological diagnosis disclosed precancerous lesions of the larynx in 34 cases and in 7 cases, squamous cell carcinoma Immunohistochemical study was performed using antibodies against the cell surface markers S-100, HLA-DR, CD20, CD45 RO, CD45 RA, and Lag. Typical dendritic cell distributions of the immunostained specimens were photographed and measured on a quantitative basis. The medical histories of the patients were then analyzed retrospectively. RESULTS: HLA-DR+ cells could be detected in 14 of 16 cases in mild dysplastic lesions. The infiltration of the dysplastic lesions was sparse compared to cases with higher-graded dysplastic lesions. The distribution patterns of the dendritic cells in specimens with severe dysplastic lesions, but squamous cell carcinoma were extremely similar and markedly different from those in grades I and II specimens. Memory T lymphocytes (CD45 RO+) were detected more often in the group with severe dysplastic lesions (8 of 9 cases) than in the group with squamous cell carcinoma (3 of 8 cases). The inverse became evident for CD20 and CD45 RA immunolabeling. CONCLUSIONS: Few dendritic cells were found in the precancerous lesions. This may suggest that these early lesions (grades I and H) are not efficiently monitored by the immune system. Therefore they may develop into carcinomas unimpaired by cytotoxic T cells. As the degree of malignancy rises (grade III), more dendritic cells infiltrate the tumor.
After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.
Specimens from 17 head and neck tumor patients were immunohistochemically stained with monoclonal antibodies against HLA-DR, CD1a, RFD1, LAG, CD3, CD4, CD8, CD45RO, CD68, and cytokeratin to identify the nature and distribution of dendritic cells (DCs), T cells, and macrophages. Small numbers of DCs were present in all but 2 specimens. They were located between the tumor cells and in the stroma, especially in areas of inflammatory cell infiltration. Variable numbers of T lymphocytes (cytotoxic and memory type) occurred in the same locations. Numerous macrophages were found in the epithelium, in the stroma, and in the vicinity of tumor cells. The presence of DCs in head and neck tumors indicates that the organism has activated the immune surveillance system and is trying to present tumor antigens. Considering the sparsity of DCs in the malignant tissues, the T cell response can be only limited.
The anatomic development of thyroglossal tract remnants is not understood at present. For analysis of morphology and growth patterns of thyroglossal tract remnants, we used histologic whole organ serial sections to determine developmental changes through the first years of life. Larynges of 58 infants and children ages 1 month to 13 years were obtained in whole organ serial step-sections in an axial plane. The slides were stained with hematoxylin and eosin, Alcian blue, and periodic acid-Schiff stains. Altogether, 3,247 histologic slices were examined. The resulting data were then correlated with the age and sex of the specimens. We found, in 24 cases (41.3%), remnants of the thyroglossal tract or ectopic thyroid tissue. In 4 specimens (16.6%), a complete thyroglossal tract could be observed that presented a ventral path in relation to the hyoid bone with no contact with the perichondrium of the cartilage. Hormonal activity of ectopic thyroid tissue was proven in 20 cases (34.5%). Thyroid follicles were located in 2 cases (3.5%) in the hyoid bone. The thyroglossal ducts revealed a modest tendency for a left-sided pathway, whereas thyroid follicles were located more on the right paramedian side. Morphometric data on the development and structure of the thyroglossal tract and the thyroid follicles during infancy and childhood are presented. The study provides quantitative data of clinical interest that elucidate the anatomy of thyroglossal tract remnants. In addition, our investigation supports Sistrunk's operative approach for avoiding recurrences in the treatment of thyroglossal duct cysts.
Several open and endoscopic surgical techniques are available to provide an adequate airway for patients with bilateral vocal cord paralysis. Transoral laser arytenoidectomy has repeatedly been reported to be a reliable and effective minimally invasive procedure for airway restoration. To our knowledge, there have been no previous reports of serious complications, other than poor vocal results, aspiration, and failed decannulation in individual patients, that have resulted from this intervention. We report a case in which arytenoidectomy led to severe complications and death. Prior irradiation is suspected to be a causative factor. To prevent such an outcome, we believe that operative settings should be chosen that avoid deep thermal injury of the laryngeal framework.
BACKGROUND: The increasing application of sophisticated methods of laryngeal framework surgery requires a profound knowledge of the size and proportions of the human larynx and its cartilaginous components. Only inadequate data regarding this subject have so far been accessible. The aim of this study was to collect exact and reliable morphometric data of the human laryngeal framework. Materials and Methods Larynges from 98 corpses (52 male, 46 female) were removed during autopsy 4-64 hours postmortem and processed without delay or fixation. Following a standard routine for preparation, 28 parameters were measured on thyroid cartilage, cricoid cartilage, arytenoid cartilage, epiglottis, and the larynx as a whole organ. None of the patients had histories or visible signs of laryngeal disease. Anatomical preparations were performed with customary surgical tools and morphometric measurements then carried out with a pair of compasses and a caliper rule. RESULTS: A total of 5,100 measurements was performed on 98 larynges. These included, aside from evaluation of the whole organ, identification of the internal and external diameters of the cricoid cartilage, height and length of the thyroid alae in different planes, angle of thyroid alae, height of arytenoid cartilage, width and length of epiglottic cartilage, and position of the anterior commissure related to the thyroid cartilage. The results provide a full scale of data determining the size and extent not only of the cartilaginous components, but of the laryngeal framework as a whole. Mean values, standard deviations, and sample sizes are given for every parameter separately for both sexes. CONCLUSION: This study provides a comprehensive and detailed description of the dimensions of the adult human larynx.
OBJECTIVE/HYPOTHESIS: Although anatomic data regarding the gross anatomy of the paranasal sinuses are available, severe complications of endonasal sinus surgery (ESS) are frequently reported. To understand and to avoid these complications, density of bony walls of the paranasal sinuses were studied in this report. Special attention was given to the analysis of the bone density in regions where minor and major complications occur in ESS. METHODS: Thirty cadaver heads were embedded in epoxy resin. The plastic blocks were sectioned with a diamond-coated wire saw into 1.0-mm thick, parallel slices in axial, coronal, and sagittal planes for 10 specimens each. The slices were x-rayed and scanned with a computerized image analyzing system. For each specimen the bone density in 12 regions of interest was measured. RESULTS: Besides the macroscopic examination of the plastinated specimens, a bone density analysis based on x-ray films is presented. Lowest bone density was found at the lateral wall of the sphenoid sinus (3.31 +/- 0.99 mm aluminum [Al]); highest density was measured at the roof of the sphenoid sinus (12.91 +/- 1.75 mm Al). Overall bone density in female specimens was 0.41 mm Al (mean) lower than in male specimens. CONCLUSIONS: This study is the first to use plastinated whole-organ serial sections and bone density images for the analysis of potential complications in ESS. The illustration of regions with minor and major bone density of the paranasal sinuses and the ethmoid floor as presented in this study may help the novice sinus surgeon to minimize the risks of ESS and to avoid severe complications.
Interleukin-15 (IL-15) is a recently described cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2. Since IL-15 was shown to stimulate human B-cell proliferation and immunoglobulin secretion, we investigated its effect on human B-cells stimulated with heat-inactivated human immunodeficiency virus type 1 (iHIV-1) in vitro. We observed a dose-dependent elevation of [3H]-thymidine incorporation and immunoglobulin production by B-cells incubated in the presence of iHIV-1. Moreover, IL-15 stimulated HIV-1-driven B-cell proliferation similarly to IL-2. As to immunoglobulin secretion, IL-15 was able to potentiate the stimulatory effect of IL-10. The highest amounts of iHIV caused a decrease in B-cell proliferation and immunoglobulin secretion to baseline levels, even in the presence of cytokines. These findings indicate that during the late stages of AIDS, when monocytes/macrophages become the major site of viral production, IL-15, in concert with other monocyte-derived cytokines, may promote polyclonal B-cell activation and hypergammaglobulinaemia, which are frequently associated with HIV infection.
The morphologic development of the human larynx during the first years of life is poorly understood to date. This study used plastinated whole organ serial sections to determine the growth and structure of the infant larynx. The larynges of 43 children 1 to 60 months old were plastinated. Whole organ serial sections were obtained by cutting the resulting specimen with a diamond band saw. The slices were then submitted to computer-assisted morphometric investigation. We found that the subglottic airway rapidly increases in size during the first 2 years of life. Further growth follows a linear mode. The relative proportion of the mucosal lining decreases likewise. In contrast to that in adults, and comparable to that in most mammals, the cartilaginous glottis accounts for 60% to 75% of the vocal folds' length at <2 years. No sexual dimorphism of the larynx exists during childhood. This study supplies detailed morphometric data on the growth and structure of the human larynx during the first years of life. It is the first to use plastinated whole organ serial sections for morphology of the pediatric larynx. Therefore, this study provides quantitative anatomic data of clinical interest that have not been available to date.
Previous studies have shown that human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DC) to replicate and spread among CD4(+) T cells. To explain the predominance of non-syncytium-inducing (NSI) over syncytium-inducing (SI) strains during the initial viremia of HIV, we investigated the ability of blood monocyte (Mo)-derived DC to transmit HIV-1 to CD4(+) cells of the monocytoid lineage. First, we demonstrate that in our system, DC are able to transmit NSI strains, but not SI strains, of HIV-1 to fresh blood Mo and to Mo-derived macrophages (MDM). To establish a productive infection, a 10-fold-lower amount of virus was necessary for DC-mediated transmission of HIV-1 to Mo than in case of cell-free infection. Second, immature CD83(-) DC (imDC) transmit virus to Mo and MDM with higher efficacy compared to mature CD83(+) DC (maDC); this finding is in contrast to data previously obtained with CD4(+) T cells. Third, maturation from imDC to maDC efficiently silenced expression of beta2-integrins CD11b, CD11c, and CD18 by maDC. Moreover, monoclonal antibody against CD18 inhibited transmission of HIV-1 from imDC to Mo. We propose that the adhesion molecules of the CD11/CD18 family, involved in cell-cell interactions of DC with the microenvironment, may play a major role in imDC-mediated HIV-1 infection of Mo and MDM.
Whole-organ sectioning is an important technique for the assessment of laryngeal pathology. Since currently established methods require prior decalcification which causes morphological changes, the critical border area between cartilage and surrounding soft tissue cannot be investigated in the same specimen and morphometric studies are not possible. Plastination is a laboratory technique that has previously demonstrated its capacity to overcome these shortcomings. In so doing water and lipids are replaced by curable polymer within the laryngeal cells making decalcification unnecessary. In the present study, more than 50 human larynges were processed using block plastination (BP) and sheet plastination (SP). For BP the complete organ was plastinated as a whole and then cut into thin serial sections. For SP the fresh organ was sliced first and plastinated in a second step. Findings demonstrated that SP allowed for the production of whole-organ sections within a period of 1 week only. Section thicknesses were as thin as 15 mm using a diamond wire saw and an ultramilling device. Sectioning was possible in both coronary and horizontal planes. Following BP, specimens were cut in an industrial cutting machine to thicknesses of about 0.6 mm. Shrinkage of tissue was less than 10% for both methods. In all, SP was technically superior to routine paraffin histology, although cutting equipment is very expensive and delicate in handling. At present the technique of BP is the method of choice for macromorphometrical investigations on serial sections of the human larynx.
Using a new application of the endoluminal approach, we were able to demonstrate the sonographic anatomy of the eustachian tube in vitro and in vivo and correlate it with the plastic-embedded specimen. Five adult normocephalic cadavers, two patients, and one specimen especially prepared for embedding in plastic were examined. A specifically developed device was used to insert the ultrasound transducer employing an endo-oral approach. The investigation was performed using an intravascular ultrasound unit. In all cases the tube could be visualized in its entirety and relevant anatomic structures identified and compared with the specimen at the corresponding levels. The deeper layers, including the paratubal structures and the mucosa, could be distinguished for the first time by means of endoluminal ultrasonography. Now that endoluminal ultrasonography has revealed this anatomic information, further studies will be able to gauge the clinical efficacy of our method in cases of ventilatory, drainage, and clearance problems. The images showed no difference between the structures in vitro and in vivo, and the vivo examination was even easier than the in vitro one owing to better tissue turgor.