Muscoplat Cc

Oral Pilocarpine for Post-Irradiation Xerostomia in Patients with Head and Neck Cancer

BACKGROUND AND METHODS We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks. RESULTS We studied 207 patients who had each received > or = 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine. CONCLUSIONS Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating.

A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients.

PURPOSE To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer. PATIENTS AND METHODS One hundred sixty-two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry. RESULTS Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups. CONCLUSION It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.

Suppression of in vitro immunoglobulin biosynthesis in bovine spleen cells by bovine viral diarrhea virus

Abstract Incubation of bovine splenic lymphoid cells with pokeweed mitogen (PWM) and bovine viral diarrhea (BVD) virus for 5 days caused a consistent, statistically significant decrease in plasma cell development (cells containing intracytoplasmic immunoglobulin) as well as IgG or IgM synthesis compared to cultures without BVD virus. Suppression of plasma cell development and immunoglobulin synthesis was not due to decreased cell viability in virus-infected cultures even though virus replication was evident in both PWM-stimulated as well as control cultures. Finally, it was shown that heat-inactivated BVD virus was not capable of suppressing either plasma cell development or immunoglobulin synthesis. Thus, these data support the hypothesis that BVD virus can alter B-cell responses, plasma cell development, and subsequent synthesis of IgG and IgM immunoglobulins.

Potential use of lymphocyte blastogenic responses in diagnosis of bovine tuberculosis

Abstract A comparison of in vitro lymphocyte responses and delayed type tuberculin skin test responses was made in an animal experimentally exposed to a Mycobacterium bovis -infected animal and in cattle naturally infected with M. bovis . Tuberculin skin tests did not suppress in vitro lymphocyte responses to M. bovis PPD and to M. avium PPD tuberculin. The whole blood test used in these studies provided for considerable savings in time as compared to use of purified lymphocytes for evaluating in vitro cellular responses. Variations in the responsiveness of lymphocytes to specific mycobacterial antigens was observed, therefore, it is recommended that profiles be established using three or more tests conducted at 14-day intervals.

Levamisole potentiation of antigen specific lymphocyte blastogenic response in Brucella abortus exposed but nonresponsive cattle

Incubation of Brucella abortus (field strain) infected and strain 19 vaccinated bovine peripheral blood lymphocytes with B. abortus antigen and levamisole caused a consistently significant increase in [3H] thymidine uptake when compared to cultures without levamisole. Levamisole did not potentiate B. abortus-induced blastogenic response of lymphocytes from non-exposed cattle. A dose response study showed that 10 micrograms/culture induced maximum potentiation of B. abortus-induced lymphocyte stimulation. Using the 10 micrograms/well concentration of levamisole, further studies were conducted to determine the net potentiation of the blastogenic responses in lymphocytes from B. abortus (field strain) infected cattle. B. abortus strain 19 vaccinated but nonresponsive and non-exposed cattle. Levamisole significantly potentiated the B. abortus-induced lymphocyte blastogenesis in lymphocytes from unresponsive cattle.

Development of a whole blood lymphocyte stimulation assay for detecting hypersensitivity to PPD in cattle experimentally infected with Mycobacterium bovis

Abstract A whole blood lymphocyte stimulation assay utilizing the uptake of tritiated thymidine was developed for the detection of Mycobacterium bovis sensitivity in cattle. Results on eight M. bovis infected animals (six to ten weeks after infection) and eight control animals show that satisfactory lymphocyte stimulation can be obtained using heparinized whole blood diluted 10-fold in tissue culture medium and cultured with purified protein derivative (PPD) for three to seven days. Infected animals exhibited significantly greater stimulation when cultured with PPD than did control animals.

Tumor associated antigens of bovine cancer eye

A study was conducted to determine the presence of surface antigens on cultured cells of bovine ocular squamous cell carcinoma (BOSCC) by serological testing. Serum from cattle with plaque and malignant stages of disease were tested for reactivity with surface antigens of cultured autologous and allogeneic cells. Indirect immune fluorescence assays were conducted to determine the presence of antibodies towards these tumor cells. It was found that sera tested possessed antibodies to the cultured tumor cells. Further, no surface reactivity was observed when these sera were tested for reactivity with normal epithelial cells. Reactive sera were analyzed by absorption tests with autologous and allogeneic cells. Absorbed sera showed no reactivity to surface antigens or allogeneic cells. This study suggests that there might be a shared antigen among the cells from plaque and malignant lesions.

Monocyte-induced potentiation of bovine fetal thymocyte mitogenic responses to concanavalin A

Peripheral blood monocytes significantly potentiated the mitogenic response of bovine fetal thymocytes to Concanavalin A as measured by incorporation of [3H] thymidine into cellular DNA. Mononuclear cells obtained from either normal or Mycobacterium bovis sensitized cattle were cultured with or without purified protein derivative (PPD) for 24 hours at which time bovine fetal thymocytes and concanavalin A were added. After 3 days of culture, both activated or non-activated monocytes significantly potentiated Con A-induced blastogenic responses. of monocytes from thymocyte cultures completely abrogated thymocyte responses to Concanavalin A.

In vitro stimulation of bovine milk lymphocytes standardization of the assay for bovine brucellosis

Abstract Lymphocytes of bovine milk origin were investigated by immunostimulation in vitro to standardize the assay for measuring the immune responses of the cells which might be useful in further understanding the immunopathology and diagnosis of bovine brucellosis. The lymphocytes were separated from whole freshly collected milk by centrifugation. The pellet of lymphocytes was washed in RPMI-1640 medium, cultured at different concentrations for different days and with Brucella abortus soluble antigen strain 1119-3 and Concanavalin A. Each culture was labelled with 1.0 μCi of methyl-[3H]thymidine 16–18 hours prior to termination of incubation at 37 C. Termination was done by cooling to 4 C. The cells were harvested for liquid scintillation counting spectrometry. In the groups of calfhood vaccinated cows and nonexposed milkers, a milk lymphocyte concentration of 2.0 × 106/ml of medium yielded a statistically significant blastogenesis. The Brucella abortus soluble antigen concentration of 4.4 μg of protein/well was found optimal to induce significant immunostimulation. A period of 4 days of incubation of the milk lymphocyte in the test was found optimal in inducing statistically significant blastogenesis in this system.

Specific in-vitro lymphocyte immunostimulation activities of Brucella abortus fractions obtained by column chromatography

Abstract A Brucella abortus soluble antigen (BASA) preparation and fractions obtained thereof, by column chromatography, were compared in terms of their ability to induce specific lymphocyte stimulation responses (LSR) in lymphocytes from cattle infected with B. abortus . Endotoxin and protein contents and the fractions were determined. The LSR induced by BASA and the fractions were compared in terms of correctly identifying samples from infected and non-infected cattle. The sensitivity and specificity for each preparation were determined and these two attributes were then correlated with endotoxin and protein content. The results suggest that lymphocyte stimulation had greater association with relative protein content than endotoxin content of the antigen preparations.