Jonathan A. Ship

MAJOR SALIVARY GLAND FUNCTION IN PATIENTS WITH RADIATION- INDUCED XEROSTOMIA: FLOW RATES AND SIALOCHEMISTRY

Radiation therapy for cancer of the head and neck region often causes salivary gland dysfunction and xerostomia. Several reports suggest that the submandibular/sublingual (SM/SL) glands may be less radiosensitive than the parotid. The purpose of this study was to evaluate differential radiation effects on the major salivary glands. Fifty patients with radiation-induced xerostomia were evaluated (33 males, 17 females; mean age 52.7). The average total tumor dose was 6034 cGy. Major salivary gland function was compared with that of 50 non-irradiated controls. Salivary flow rates included unstimulated and stimulated flows of both the parotid and SM/SL glands. Sialochemical analyses included total protein, lysozyme, lactoferrin, sodium, chloride, and potassium. All four measures of salivary flow were significantly reduced in patients as compared to controls (p = .0001). Like the parotid, submandibular/sublingual gland dysfunction appears to be radiation dose- and field-dependent. Patients in the lowest radiation dose quartile (< or = 5000 cGy) had significantly increased salivary flow compared to those in the highest dose quartile (> or = 6800 cGy; p = .025). Glands that were partially irradiated were more likely to have some residual function than fully irradiated glands (p = .003). Lactoferrin content was increased in parotid saliva of radiation patients (p = .0001). Chloride content was significantly increased also (p = .0001). The SM/SL glands are clearly dysfunctional in post-irradiation xerostomia patients compared to controls, in terms of both flow rates and sialochemistry.

EPIDEMIOLOGY OF ACQUIRED IMMUNE DEFICIENCY SYNDROME IN PERSONS AGED 50 YEARS OR OLDER

SummaryAcquired immune deficiency syndrome (AIDS) has afflicted persons of all ages, yet only recently has attention been devoted to AIDS in older persons. To examine the epidemiology of AIDS in persons ≧50 years old in the United States, we analyzed cases reported to the Centers for Disease Control. The number reported annually in persons ≧50 years old increased from 13 in 1981 to 3,562 in 1989. Through December 1989, 11,984 had been reported, representing 10% of all cases. Although male homosexual contact accounted for most cases in persons aged 50–69, blood transfusion became a more common means of exposure with increasing age, accounting for 28% of cases in persons aged 60–69 and 64% of cases in individuals aged ≧70. The proportion of women increased from 6.1% in persons with AIDS aged 50–59 to 28.7% of those aged ≧70. The proportion of AIDS diagnoses made in the same month as death increased from 16% in persons aged 50–59 to 37% in those aged ≧80, suggesting either more rapid progression of disease or increasing delay in diagnosis. As the incidence in older persons continues to increase, clinicians caring for older patients must become more familiar with AIDS.

Oral mucosal status and major salivary gland function

Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjögrens syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity.

Salivary Gland Function and Aging: A Model for Studying the Interaction of Aging and Systemic Disease

This review describes an approach to examining the interaction of aging and systemic disease on a key aspect of oral physiology, salivation. The approach requires several steps: defining general health, and a specific physiological function, at different ages; defining a disease of interest and the influence of the disease on the specific physiological function; and determining if the disease can affect performance of the physiological function with increased age.

Oral mucosal appearance is unchanged in healthy, different-aged persons

Oral mucosal status in 182 different-aged, healthy, community-dwelling persons was evaluated. Ninety-four men and 88 women, ranging in age between 20 and 95 years, participated in this study. Oral mucosal status was assessed according to both subjective complaints and a semiquantitative clinical rating scale. No changes in either criterion were detected with increasing age. Oral mucosal status of the older subjects of this study was comparable to that found in a previous study with a randomly enrolled, noninstitutionalized older population in Iowa. The results of this study suggest that aging per se does not lead to changes in the appearance of oral mucosa.

Oral Health in Patients With Type II Diabetes and Impaired Glucose Tolerance

OBJECTIVE To assess the influence of type II diabetes and impaired glucose tolerance on dental, periodontal, and oral mucosal tissues. RESEARCH DESIGN AND METHODS We examined 11 subjects with type II diabetes, 32 with impaired glucose tolerance, and 43 control subjects from the oral physiology component of the Baltimore Longitudinal Study of Aging. At the time of the study, none of the participants was taking medication nor being treated for any medical problems other than diabetes. RESULTS Only a few statistically significant dental and periodontal changes were apparent in the group with type II diabetes, and no oral mucosal differences existed between the diabetes and control groups. Dental, periodontal, and oral mucosal parameters in patients with impaired glucose tolerance were essentially indistinguishable from the other two groups. CONCLUSIONS These findings suggest that among well-controlled individuals with type II diabetes and impaired glucose tolerance, few appreciable differences are evident in oral health.

β-Adrenergic responsiveness in a human submandibular tumor cells line (A253)

SummarySalivary epithelial functions are regulated by the autonomic nervous system. In this regard, we have been studying the morphology and neuroreceptor composition of A253, an immortal cell line isolated from a human submandibular carcinoma (Giard et al., JNCI, 51:1417–1421, 1973). Phase contrast and electron microscopic observation indicate that A253 cells are of epithelial origin. Physiologically, A253 cells posses β-adrenergic, but not α-adrenergic or muscarinic-cholinergic receptors. The β-adrenergic receptors (BARs) are composed primarily of a single class of high affinity, β2-subtype receptors as judged by [3H]dihydroalprenolol antagonist binding studies. The BARs are functional inasmuch as isoproterenol stimulation increases both intracellular cAMP content and [3H]mannose incorporation into endogeneous glycoproteins. Differences in ultrastructure and neuroreceptor composition between A253 and other immortal salivary tumor cell lines are discussed.

N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (w7) stimulation of K+ transport in a human salivary epithelial cell line

Treatment of a human salivary epithelial cell line, HSG-PA, with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7; 20-70 microM) increased 86Rb (K+) influx and efflux in a manner similar to that resulting from muscarinic (carbachol; Cch) or calcium ionophore (A23187) stimulation. Unlike the Cch or A23187 responses, the W7 responses were not blocked by 0.1 mM atropine (muscarinic antagonist) or phorbol-12-myristate-13-acetate (0.1 microM). Like Cch- or A23187-stimulated 86Rb fluxes, W7-stimulated 86Rb fluxes were substantially blocked by the K+ channel inhibitors quinine (0.25 mM) and scorpion venom-containing charybdotoxin (33 micrograms/mL), while 5 mM tetraethylammonium chloride (K+ channel blocker), furosemide (0.1 mM; Na+,K+,2Cl- co-transport inhibitor) and ouabain (10 microM; Na+,K(+)-ATPase inhibitor) were ineffective. Purified charybdotoxin (10 nM) also blocked W7-stimulated 86Rb influx, as well as 86Rb influx stimulated by Cch or A23187. Although Quin 2 fluorescence measurements indicated that W7 increased free intracellular Ca2+ concentration ([Ca2+]i), the magnitude of the increase appeared to be insufficient to solely account for the W7-stimulated increases in 86Rb fluxes (i.e. K+ channel activity). Ca2+ was involved in the W7 response, however, as lack of Ca2+ in the incubation medium reduced the W7-stimulated increases in 86Rb influx and efflux. Taken together, our results suggest that W7 increased K+ fluxes in HSG-PA cells by interacting, directly or indirectly, with the K+ transport machinery (K+ channels) in a manner different from that observed during muscarinic stimulation, and also in a manner not accounted for solely by the formation of a typical muscarinic- or calcium ionophore-generated calcium signal.