Diffuse reflectance spectroscopy of the human tympanic membrane in otitis media.

We have investigated if features in the diffuse reflectance spectra from in vivo spectroscopic measurements of the tympanic membrane could aid the diagnosis of otitis media in children. Diffuse reflectance spectroscopy, in the visible wavelength range, was used in 15 ears from children with otitis media with effusion before and after myringotomy and in 15 healthy ears as a reference. Two previously published erythema detection algorithms yielded numerical quantities of haemoglobin content. With a combination of the algorithms, induced erythema (after myringotomy) was distinguished from healthy ears using Student's t-test (p < 0.01). Otitis media with mucous effusion was distinguished from (1) otitis media with serous effusion, (2) induced erythema and (3) healthy ears, (p < 0.05) using Student's t-test for independent groups and the paired t-test for dependent groups. Our results imply that reflectance spectroscopy is a promising technique to be used for the diagnosis of otitis media.

Effect of carbon dioxide on cochlear blood flow in guinea pigs.

The influence of carbon dioxide (CO2) on cochlear blood flow (CBF), blood pressure (SBP) and skin blood flow (SBF) was studied in anaesthetized guinea pigs. A transient acute respiratory acidosis was produced by inhalation of CO2 and oxygen (O2) gas mixtures. The blood flows were measured by laser Doppler flowmetry (LDF). High CO2 increased CBF and SBP, and decreased SBF in a dose-dependent manner. The responses of CBF, SBP and SBF to high CO2 were reversible. Our results indicate that high CO2 (and low pH) dilates the smooth muscle of the blood vessels, resulting in an increase in CBF. CO2 also activates the sympathetic nervous system in the whole body, producing an increase in SBP. The distribution of alpha-adrenergic fibres receptors is abundant in skin and scarce in the cochlea. The constrictive effect on blood vessels is much greater in the skin than in the cochlea, thus our results showed a decrease in SBF during stimulation with higher CO2.

Essential dataset for ambulatory ear, nose, and throat care in general practice: an aid for quality assessment.

OBJECTIVE: To describe the documentation of care for the usual range of ear, nose, and throat (ENT) problems seen in primary care as a basis for developing a computerised information system to aid quality assessment. DESIGN: Descriptive study of the pattern of ENT problems and diagnoses and treatment as recorded in individual case notes. SETTING: The primary health care centre in Mjölby, Sweden. PATIENTS: Consultations for ENT problems from a 10% sample randomly selected from all consultations (n = 22,600) in one year. From this sample 375 consultations for ENT problems (16% of all consultations) by 272 patients were identified. MAIN MEASURES: The detailed documentation of each consultation was retrieved from the individual records and compared with the data required for a computer based information system designed to help in quality management. RESULTS: Although the overall picture gained from the data retrieved from the notes suggested that ENT care was probably adequate, the recorded details were limited. The written case notes were insufficient when compared with the details required for a computerised system based on an essential dataset designed to allow assessment of diagnostic accuracy and appropriateness of treatment of ENT problems in primary care. CONCLUSION: There is a gap between the amount and the type of information needed for accurate and useful quality assessment and that which is normally included in case notes. More detailed information is needed if general practitioners' notes are to be used for regular quality assessment of ENT problems but that would mean more time spent on keeping notes. This would be difficult to justify. IMPLICATIONS: The routine information systems used at this primary healthcare centre did not produce sufficient documentation for quality assessment of ENT care. This dilemma might be resolved by specially designed desktop computer software accessed through an essential dataset.

Prognostic significance of DNA ploidy in mucoepidermoid carcinoma.

Thirty-four mucoepidermoid carcinomas were studied retrospectively with regard to histological and clinical parameters. In 28 of the tumors DNA patterns were also assessed using flow cytometry. Twenty-two of the 28 tumors (79%) were DNA diploid and 6 (21%) DNA aneuploid. Two tumors (7%) showed intratumoral DNA as indicated by different stemlines in specimens investigated from different parts of the tumor. DNA ploidy correlated significantly with cervical lymph node status (P < 0.01), but not with tumor size or histological grade. The mean S-phase value was 2.7% and was significantly higher in aneuploid samples than in diploid ones (P < 0.05). The recurrence rate was significantly lower for patients with stage I and II tumor compared with those with stage III and IV disease (P < 0.01). Five aneuploid tumors showed significantly higher recurrence rates (5/6) than the diploid ones (1/22) (P < 0.01). In univariate analysis for survival, only N stage tumor (P < 0.05) and tumor DNA ploidy (P < 0.0003) had significant prognostic influence. Thus, DNA ploidy seems to be a valuable parameter for evaluating the biological behavior of mucoepidermoid carcinomas of the salivary glands.

Adenoid cystic carcinoma: significance of DNA ploidy.

BACKGROUND: DNA ploidy pattern is sometimes used as a prognostic factor. Heterogeneity of a tumor could, however, give false information when a single analysis is performed. METHODS: Twenty-eight patients with adenoid cystic carcinomas were retrospectively studied with regard to clinico-histologic parameters, and in 24 of these the DNA pattern was assessed using flow cytometry, with multiple analysis from different tumor parts, to determine prognostic factors. RESULTS: Of the carcinomas, 33% (8/24) were DNA aneuploid, and 17% (4/24) of the tumors showed intratumoral heterogeneity of DNA content; two of them with mixture of diploid and aneuploid stemlines. The DNA aneuploid tumors were clinically more advanced and demonstrated a higher frequency of solid architecture than did diploid tumors (p < 0.05). The S-phase values were significantly higher in aneuploid samples than in diploid ones (p < 0.05). The recurrence rate was significantly higher in patients with aneuploid tumors (75%) than with diploid ones (19%) (p < 0.05). The cumulative survival was worse for patients with aneuploid tumors than for those with diploid ones (p < 0.05). CONCLUSIONS: Our findings suggest a potentially important role for flow cytometry in evaluation of adenoid cystic carcinoma. It is of interest to observe that in some tumors both diploid and aneuploid stemlines can co-exist. If one sample is analyzed and demonstrates diploid cells, there is a 3% chance that the tumor is also heterogeneous with aneuploid stemlines. If one sample demonstrates aneuploid cells, there is a 7% chance for heterogeneity with diploid cells, as well. Two samples from different tumor parts can be considered representative.

Towards an essential data set for ambulatory otorhinolaryngological care in general practice.

In order to optimize otorhinolaryngological ambulatory care provision and quality assurance in the general practice services there is a need for interdisciplinary consensus on the conditions, the quantitative and qualitative criteria of diagnosis and outcome as well as other standards that apply to such a partnership. We report on the core, or essential set, of data involved herein, as derived from an information modelling study of the literature and a formalized agreement between the public primary health care and specialist otorhinolaryngology organizations in Sweden. We find that the identified essential data set constitutes a compact common taxonomy, term register, or thesaurus, an ordered survey of which provides the necessary performance and quality assurance support. This points to a computerized method of mediation. The essential data set for otorhinolaryngology in general practice thus corresponds to the notion of a basic minimal data set as outlined by the World Health Organization to be one of the requisites for the successful realization of the distinct components of the Health for All by the Year 2000 programme at the local level.

Heterogeneity of salivary gland tumors studied by flow cytometry.

Intratumor DNA heterogeneity was investigated by flow cytometric analysis of multiple samples taken from different sites of 8 benign and 16 malignant primarily resected salivary gland tumors. All benign tumors had diploid DNA content. The overall incidence of DNA diploidy in 16 malignant cases examined was 50%. Intratumor differences in DNA ploidy were observed in four malignant tumors (25%); 2 of these 4 heterogeneous tumors contained both aneuploid and diploid cell clones. The remaining 12 tumors showed a homogeneous DNA content in the different specimens; 8 were diploid, 3 aneuploid, and 1 was polypoid. The DNA nondiploid tumors were clinically more advanced than the DNA diploid ones (p < 0.01). The tumor proliferation rate (fraction of cells in S-phase) was higher in DNA nondiploid samples than in diploid ones (p < 0.01). The DNA nondiploid tumors seemed to recur more often than DNA diploid ones did. The data emphasize the usefulness of DNA measurements for the characterization of malignant salivary gland tumors but also the importance of adequate sampling in assessing their DNA ploidy.

Ultrastructural changes in salivary glands after different adrenergic and cholinergic stimulations. A long-term morphological study in the rat.

We have compared four different sialogogues and their degranulating effect on serous and mucous cells, and their long-term effects. From this and earlier experiments, even within the groups of alpha- and beta-adrenergic agents used, the effects varied on the serous and mucous cells. Previous studies have shown that cyclocytidine effectively degranulates serous cells without signs of cellular damage, while carbachol predominantly affects mucous acinar cells but gives early rise to permanent gland damage. Noradrenaline affects both serous and mucous cells, predominantly affecting serous cells with initial mitochondrial damage. Clonidine partially depletes both serous and mucous cells of their granules, producing permanent cellular damage. One month after a single injection of cyclocytidine the early findings described had disappeared. Carbachol showed permanent damage to salivary gland parenchyma, and both noradrenaline and clonidine demonstrated a long-term effect on acinar mucinous cells.

Studies on the regranulation of salivary gland serous cells. An electron microscopical study in the rat.

The degranulation and regranulation process was investigated after alpha-adrenergic stimulation on the rat submandibular gland. The submandibular gland in rat contains both serous and mucous cells. It has earlier been shown that serous cells filled with heavy-metal granules, are markedly more radiosensitive than cells without granules. In experiments with emptying the serous cell of their content of granules by administering an alpha-adrenergic stimulant, cyclocytidine, there has been found a decrease in irradiation damage in salivary gland tissue after irradiation. Injection of cyclocytidine, 150 mg/kg, was given i.p. to the rat. After 1 h there was almost complete depletion of granules in the serous cells, no morphological aberration was seen in the mucous cells. This effect still remained after 6 h. A beginning of regranulation with apical granules was seen 12 h after injection. After 24 h an almost complete regranulation had occurred in the salivary gland serous cells. The mucous cells did not show any morphological aberration. Our intent is to reduce unwanted salivary gland damage in patients with head and neck cancer when treated with radiotherapy. Depletion of heavy-metal granules in serous cells, before irradiation may diminish morphological destruction in the salivary glands. As a nearly total degranulation is present between 1-6 h after stimulation, this should be the optimal time for radiotherapy.

Morphological changes in salivary glands after treatment with sialagogues. An electronmicroscopical study.

A dual innervation in salivary glands has been discussed. It is unclear how alpha-adrenergic and cholinergic agents stimulate the secretory cells. Different effects on serous and mucous cells are reported after stimulating with carbachol, clonidine, noradrenaline, cyclocytidine and pilocarpine, respectively. In the rat, carbachol and clonidine predominantly affect the mucous cells, however, with different morphological effects. Cyclocytidine exclusively degranulates the serous cells. Noradrenaline stimulates both serous and mucous cells and gives rise to vast cytoplasmic changes. Pilocarpine only shows effect on the mucous cells with formation of intracytoplasmic vacuoles. The effects reported are discussed with regard to experiments on salivary gland radiosensitivity.

Aspects of salivary gland radiosensitivity: effects of sialagogues and irradiation.

Rat submandibular glands were exposed to fractionated irradiation of 50 Gy, as given comparably in clinical practice. The induced changes were compared by giving only irradiation or radiation in conjunction with stimulating the salivary glands with cyclocytidine prior to treatment. Cyclocytidine is an alpha-adrenergic agonist that effectively depletes the serous cells of their granules and their heavy metal content. Findings in the present study show that the administration of the drug prior to each irradiation reduces the radiation-induced destruction in the epithelial cells in the submandibular gland.

Effects of ligation and irradiation on the submaxillary glands in rats.

Rat submaxillary glands were exposed to excretory duct ligation, high-energy electron irradiation, or a combination of both. Ligation was done on the left excretory ducts, while 24 Gy irradiation was given within 8 days in three divided doses of 8 Gy. In the combined insults, the excretory ducts (one duct per rat) were first ligated, followed by 24 Gy irradiation. The effects were analysed by morphological methods. Ligation of excretory ducts caused morphological disorganization of the gland parenchyma, with resultant disappearance of secretory granules of serous cells, shrinkage of mucous cells, dilation of ducts, pronounced fibrosis and infiltration of inflammatory cells. When irradiated, some serous cells disappeared, leaving empty fibrosed spaces, while mucous cells showed no consequential radio-damage. The combined treatment of ligation of excretory ducts and irradiation caused extensive morphologic evidence of irreversible damage, i.e. no serous cells remained, disfigured and very shrunk mucous cells extremely dilated ducts, infiltration of leukocytes and fibrotic changes of the glands.

An ultrastructural study of salivary gland radiosensitivity after alpha-adrenergic stimulation.

The submandibular glands in 32 rats were exposed to either fractionated irradiation comparable to 50 Gy or a single fraction of 50 Gy. Prior to irradiation half the rats were given cyclocytidine, an alpha-adrenergic agonist which depletes serous cell granules. The results suggest that irradiation causes a significant, irreversible destruction of serous cells. Visible morphological changes were: intracytoplasmic vacuoles, destroyed mitochondria with disrupted cristae and derangement of the endoplasmic reticulum. Animals treated with cyclocytidine had diminished radiation injury. This drug may act as radioprotector, depleting secretory heavy metal granules, reducing radiation damage in the submandibular salivary glands.

Radiation-induced decreases of serous cell immunoglobulin excretions in the rat submandibular gland.

The effect of radiation on the submandibular glands of the rat was studied with special reference to the immune reactivity of IgG and IgA. These immunoglobulins are localized in the serous cells and were influenced by irradiation. Radiation therapy markedly reduced the reactivity for both IgG and IgA. Immunocytochemistry showed a good correlation to the deteriorated morphology as revealed by light and electron microscopy. The local excretion of immunoglobulins in the submandibular gland can thus be affected by radiation and results in an increased risk for oral infections. Pretreatment of animals with the secretagogue cyclocytidine caused less pronounced damage in cellular ultrastructure and immunological findings, as observed by fluorescence microscopy.

Salivary gland morphology after alpha-adrenergic and cholinergic stimulation. An ultrastructural study.

The submandibular glands in 100 rats were subjected to different sialagogues: carbachol, clonidine, noradrenalin, and cyclocytidine. The morphological effects of these drugs were compared ultrastructurally. Clonidine, which is an alpha-2-agonist affected mostly the mucous cells, with formation of cytoplasmic vacuoles between the mucous droplets. Noradrenalin and cyclocytidine, both alpha-1-agonists, showed depletion of secretory granules in the serous cells. Noradrenalin also induced cytoplasmic disorganization with enlarged mitochondria, irregular endoplasmic reticulum, and shrinking of the secretory lumen. Carbachol, a cholinergic agonist, was found to produce widespread vacuolization in the cytoplasm of both serous and mucous cells. Small vesicles appeared and mitochondria were destroyed. To induce experimentally a complete depletion of granular serous cells, without other changes in ultrastructural morphology, cyclocytidine was found to be the most efficient drug.

Salivary calculi and chronic sialoadenitis of the submandibular gland: a radiographic and histologic study.

This study correlated radiographic observations and histologic findings of submandibular glands with the diagnosis of salivary calculus and/or chronic sialoadenitis. During a 15-year period eighty-eight patients satisfied clinical requirements by having a radiographic examination performed prior to gland extirpation. Salivary calculi were present in 83% of the patients. The diagnostic accuracy of radiographs regarding salivary calculi in the submandibular gland system was 92%. Radiolucent calculi constituted 20% of the total number of cases with concrements. Failure to disclose concrements was caused by lack of contrast filling due to a damaged gland which presumably camouflaged radiolucent concretions. Ductal changes observed in sialograms corresponded to histologic changes in the glandular parenchyma in 96% of the cases. The absence of ductal change in sialograms did not necessarily indicate a nondiseased gland.

Interferon therapy in juvenile laryngeal papillomatosis.

Seventeen patients with severe juvenile laryngeal papillomatosis (12 in Stockholm and five in Umeå) were treated with exogenous leukocyte interferon (IFN-alpha) prepared in Helsinki and Umeå, respectively. Tumor progression occurred in all cases before treatment. During treatment tumor growth diminished in all cases, up to complete tumor disappearance. Of 17 patients, nine were cured and no longer are being treated, four exhibit no tumor growth but are still being treated, one has visible tumor but only slight growth, two still have active but diminished growth, and one, who has refused further treatment, is experiencing active tumor growth as before the start of interferon therapy. It is concluded that IFN-alpha therapy in a dosage of 3 X 10(6) units three times a week intramuscularly can arrest papilloma growth. Further trials are needed to optimize treatment.