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Biomedical subjects

P G Lundquist

Publications and source records attributed to P G Lundquist.

At least 19 recordsLinked to original sources

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.

Ancitabine

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.

Ancitabine

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.

Ancitabine

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.

Adrenergic alpha-Agonists

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.

Adrenergic alpha-Agonists

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.

Adolescent

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.

Adolescent

Combined preoperative radiotherapy and surgery in the treatment of carcinoma of the anterior two-thirds of the tongue.

Sixty-three patients with squamous cell carcinoma of the anterior two-thirds of the tongue were treated with preoperative external radiotherapy (mean target dose 42.60 Gray or 4260 rad) and surgery. The expected 5-year survival, expressed as life table estimate of percent of survivors, was 77% for patients with Stage I tumors, 69% with Stage II, and 13% for patients with tumors in Stages III-IV (p less than 0.001). Fourteen patients experienced local recurrences, 7 had homolateral neck metastases, 4 had contralateral neck metastases and 3 had distant metastases. In 15 cases no cancer could be detected at review of the surgical specimens, but 2 of these died of their cancers. In 43 cases cancer was present in the specimens, and 26 of these died of their cancer (p less than 0.01).

Adult

Experiments on cochlear cryosurgery in the guinea pig.

A method to induce experimental cochlear lesions with cryosurgery is described. Using temperatures on the cochlear surface ranging from 0 degrees C-50 degrees C, lesions were made from the apical turn and down to 8 mm from the round window area. There were no signs of labyrinthine fistula and the remaining parts of the organ of Corti were normal in appearance. The correlation of intracochlear temperature with the spread of anatomical damage is described. It is suggested that this method can be used to achieve non-invasive selective cochlear lesions. With this method it is probably possible to induce sensory-neural lesions not only in the high frequency region of hearing, but also in the middle and low frequency regions.

Animals

The hearing of symphony orchestra musicians.

The question has recently been raised as to whether the performance of symphony orchestra music involves a risk of sustaining hearing impairment. The following investigation presents a population study of 417 musicians, of whom 123 were investigated twice, at an interval of 6 years. Median values of screened tone thresholds were compared with a reference material, according to Spoor & Passchier-Vermeer (1969). The tone thresholds measured did not differ from the reference values although the actual sound exposure in some situations exceeded the permitted sound levels applied to industrial noise. We suggest that the sound exposure criteria for industrial noise are not valid when discussing such sounds as are produced by acoustic instruments in a symphonic environment.

Adult

Methotrexate and 5-fluorouracil in head and neck cancer.

Since experimental data strongly suggest a synergistic cytotoxic effect when methotrexate (MTX) and 5-fluorouracil (5-FU) are administered sequentially, we investigated antitumor effects and toxicity with sequential MTX/5-FU followed by leucovorin rescue in 52 patients with carcinoma of the head and neck. MTX (200 mg/m2) was given as an i.v. infusion over 1 hr. At 2 hr, 5-FU (600 mg/m2) was started as an i.v. infusion for 2 hr. At 24 hr, the leucovorin rescue was started. The chemotherapy course was repeated every week until toxicity (mainly gastrointestinal) occurred, after which the interval between courses was prolonged to 2 wk. Toxicity was mild and usually disappeared when the interval between the chemotherapy courses was prolonged to 2 wk. The regression rate was 15% for complete and 48% for partial regression (response rate, 63%). In 31 of the patients not previously treated, the objective response rate was 74%. About the same results were obtained for tumors of different anatomic sites of the head and neck. Radiotherapy could be added sequentially without measurable escalation of toxicity. We conclude that sequential MTX/5-FU treatment, which produces a very mild toxicity to normal tissue, is effective in inducing antitumor response in patients with carcinoma of the head and neck.

Carcinoma, Squamous Cell

The sensory epithelia of the human labyrinth. A freeze-fracturing and transmission electron microscopic study.

The end-organs of the human vestibular system were studied with transmission electron microscopic and freeze-fracturing techniques. The general morphology of the sensory epithelia was comparable to that of animals. The hair cells consisted of flask-shaped type I hair cells with the surrounding nerve calyx and rod-shaped type II hair cells contacted by several small bouton-shaped nerve endings. The hair cells were coupled to neighboring supporting cells by tight junctions at the lateroapical aspect. These were regular in appearance and of the moderately tight type. This type of tight junction has been found elsewhere in the inner ear and is believed to be competent to maintain its unique ion composition. The lateral surfaces of the supporting cells were coupled by gap junctions. The afferent nerve terminal of the type I hair cell, the so-called calyx, totally encompassed the hair cell. It could not be concluded on the basis of the present material whether the type I hair cell-calyx complex mediates electrical or chemical synaptic contact. The synapses of afferent nerves on type II hair cells, however, displayed typical signs of being chemically mediated. Synaptic bodies, similar to those seen in animals, were associated with the presynaptic membrane inside the hair cell. Membrane specializations comparable to those of animals were also seen in these synapses. Efferent nerve endings and synapses were not readily identified and were thus not discussed in this study.

Cell Membrane

The fenestrated blood vessels of the endolymphatic sac. A freeze-fracture and transmission electron microscopic study.

The fenestrated blood vessels surrounding the endolymphatic sac in guinea pigs were investigated with the help of freeze-fracturing. The technique exposes the structure and distribution of vascular pores as well as interendothelial bridges or tight junctions between vascular endothelial cells. It is possible to get a three-dimensional comprehension of the vascular structure which can be compared with that of conventional transmission electron microscopy (TEM). Discontinuity in the junctional elements as seen in some endothelial layers and the high number of fenestrations organized in geometric patterns, as well as the abundant, randomly distributed micropinocytotic vesicles seem to bear out the theory that the endolymphatic sac is one of the most metabolically active parts of the inner ear and may be involved in the turnover of endolymph.

Animals

Salivary calculi as an aetiological factor in chronic sialadenitis of the submandibular gland.

During 1960-1975, 115 submandibular glands were removed for reasons other than neoplasia at the Ear, Nose and Throat department, Karolinska sjukhuset, Stockholm. The material was retrospectively analysed with regard to clinical and histopathological findings. The patients, 62 men and 52 women aged 13-77 years, exhibited in all cases but one a chronic sialadenitis. Salivary calculi were found in 82% of the patients. In one patient a mucous retention cyst was found. Microscopically some cases exhibited only a slight periductal inflammation, while others showed a complete destruction of the gland architecture. The duration of symptoms of the whole group before surgery varied from 1 week to 55 years but with a median value of almost 1 year. The conclusion of this study is that salivary calculus is the most important indication for removal of submandibular gland, for reasons other than neoplasia.

Adolescent