Cochlear implants: 100 pediatric case conversions from the body worn to the nucleus esprit 22 ear level speech processor.

OBJECTIVE: To assess performance of Nucleus 22 mini system pediatric users converted from the Spectra 22 body-worn to the ESPrit 22 ear-level speech processor using aided thresholds and speech discrimination measures before and after the conversion. STUDY DESIGN: Spectra 22 body-worn speech processor users were chosen using preselection criteria (stable map, ability to report on the quality of the signal, no device problems). The subjects underwent tuning, map conversion, fitting of the ESPrit 22, and aided soundfield threshold and speech discrimination testing. SUBJECTS: The first 100 consecutive conversions are analyzed in this study. Fifty children (50%) were female, and 50 (50%) were male. The average age at implantation was 4.6 years (median 4.3 years, range 1.7 to 11 years). The average age of fitting the ear level speech processor was 11.1 years (median 11 years, range 6.2 to 18.2 years). SETTING: Tertiary referral pediatric cochlear implant center in the United Kingdom. RESULTS: Of the 100 fittings attempted, all Spectra 22 maps could to be converted for use in the ESPrit 22. Of these 100 fittings, 44 were straightforward with no adjustment to map parameters being required, and 56 needed rate reductions and other map adjustments to achieve the conversion. The difference of the mean thresholds before and after the conversion did not exceed 2 dB across the frequencies studied (0.5-4 kHz). In 95% of the cases, the differences were less than 9 dB(A). With regard to speech discrimination testing, the mean threshold before the conversion was 53.4 dB and after the conversion 52.7 dB. Of the 100 conversions, only five children stopped using the ESPrit 22 despite fitting being achieved. CONCLUSION: Conversion from the Spectra 22 body worn to the ESPrit 22 ear level speech processor was found to be feasible in all the 100 cases studied. Only a minority (5%) of children chose not to use the ear level speech processor suggesting that children and parents were satisfied from the conversion.

Morphological abnormalities of lymphocytes from patients with advanced solid tumours.

Characteristic morphological abnormalities were found to be present on lymphocytes from patients with advanced solid tumours. Numerous microprojections were characteristically present on human peripheral blood lymphocytes from cancer patients while non-cancer subject control lymphocytes ('normal' lymphocytes) appeared significantly smoother. Incubation of normal lymphocytes in cancer serum resulted in increased occurrence of these microprojections whereas incubation of normal cells in normal heterologous serum resulted in no apparent surface changes. Incubation of cancer lymphocytes in levamisole, an immunostimulant, did not abrogate surface projections.

Immune suppression by cultured lymphocyte supernates of tumor-bearing hosts.

A nonspecific immunosuppressive factor produced by lymphocytes of tumor-bearing hosts has been demonstrated. A modified Jerne plaque was used to quantify IgM antibody production of sheep erythrocyte-immune Swiss mouse lymphocytes (IL). Significant suppression of IgM antibody production was found when IL were treated with cultured lymphocyte supernates of 4198 fibrosarcoma-bearing mice. The suppressive activity was found to be significant six days prior to any visible tumor development, and, through the use of glass and nylon wool columns, appears to be produced by T cells. Similar immunosuppressive activity was found in 22 cancer patients tested as above, compared either to 16 patients who previously had had solid tumors but are now without clinical disease or to 19 normal controls.

Release of soluble "blocking" and "suppressor" factors from normal lymphocytes treated with RNA from spleens of tumour-bearing mice.

RNA extracted from the spleens of tumour-bearing (TLRNA) and tumour-immune (ILRNA) mice was shown to transfer to normal lymphocytes (NL) the ability to produce factors that blocked specific tumour-cell cytotoxicity and mediated specific antibody-dependent cell cytotoxicity (ADCC). Aliquots of normal C3H mouse lymphocytes were treated with TLRNA or ILRNA and cultured in vitro in the absence of tumour antigen. Supernatants were collected at 24h intervals and tested in a microcytotoxicity assay for blocking and ADCC activities. Factors that inhibited tumour destruction by specifically sensitized lymphocytes at the level of both the tumour cells and effector cells were demonstrable in culture supernatants of NL pretreated with TLRNA (50 or 100 microgram/4 X 10(6) cells) but not ILRNA. However, treatment of NL with either RNA resulted in the production factors that mediated tumour-specific ADCC. Cytotoxicity testing and absorption studies of the tumour cell and a control cell (LM) indicated that factors mediating ADCC and blocking at the target-cell level were specific for the tumour. Suppressor activity at the effector-cell level was not absorbed by tumour cells and represents a separate and distinct mechanism of immunosuppression. These data indicate that RNA faithfully transfers "suppressive" as well as "positive" types of immune responses that have been reported previously for lymphocytes obtained directly from tumour-bearing and tumour-immune animals.

Immunotherapy of a murine sarcoma using specific antitumor immune RNA.

The effect of IRNA therapy in a polyoma-induced fibrosarcoma of C3H mice has been studied. Although a protocol that transferred in vitro cytotoxicity was used, no reduction in incidence of tumors, tumor size, or survival was demonstrated. In one experiment, enhancement of tumor growth occurred. It is concluded that cytotoxicity does not reflect in vivo changes and that therapeutic trials of IRNA are premature.

Anti-tumour cytotoxicity of poly(A)-containing messenger RNA isolated from tumour-specific immunogenic RNA.

The transfer of tumour-specific cytotoxicity against a murine fibrosar-coma has been demonstrated in vitro using xenogeneic RNA extracted from tumour-cell-immune animals. Poly(A)-tailed messenger RNA from immunogenic RNA was isolated by passage through an oligo(dT)-cellulose column, and evaluated to determine whether the same tumour-specific cytotoxicity could be transferred. Aliquots of normal C3H mouse lymphocytes were treated with poly(A)-containing immune RNA, whole-cell immune RNA lacking poly(A) and total cellular immune RNA. Treated cells were tested in vitro using an adaptation of the Takasugi and Klein microcytotoxicity assay. Percent cytotoxicity was calculted using cells treated with fractions of normal RNA as control. An increase in tumour cytotoxicity was found with poly(A)-containing immune RNA. The optimum dose of poly(A)-tailed immune RNA was estimated as 6.5 microgram of RNA per 4 x 10(6) lymphocytes. Populations of lymphocytes were separated using glass and nylon wool. T- and B-enriched populations were treated with various RNA components. The adherent cell population showed no significant cytotoxicity, whilst treatment of the nonadherent population with poly(A)-tailed immune RNA produced high levels of cytotoxicity.

The effect of Corynebacterium parvum on the humoral and cellular immune systems in patients with breast cancer.

Corynebacterium parvum, a Gram-positive anaerobic bacillus thought to be a strong immunological stimulant, has been shown to decrease tumour growth and prolong survival in patients with metastatic disease. Study of the effect of a single injection of a strain of C. parvum (CN. 6134) in six patients with stage IV metastatic breast cancer is reported. Results of laboratory tests to judge the physical and immunological effects of the drug infusion 24 hr post-treatment and weekly thereafter for 3 weeks are evaluated. Within 24 hr after C. parvum administration, most patients experienced fever and nausea. Blood counts and differential counts exhibited increased values 24 hr after treatment with a strong shift to the left. Lymphocyte and monocyte counts were greatly depressed at 24 hr. T-cell numbers in peripheral blood did not appear to be altered, but the picture with regard to B cells was less clear. Normal count was recovered by day 8. It appears that intravenous administration of C. parvum produces a temporary marked immunological depression which returns to essentially normal values in 8 days. The return to normal may be accompanied by resolution of the endotoxin-like syndrome of side-effects. Further study of patients receiving this therapeutic agent is important to detect enhancement of the anti-tumour immunological response precipitated.

Cellular immunity in neoplasia. Antigen and mitogen responses in patients with bronchiogenic carcinoma.

Cellular immune responses of patients with histologically confirmed lung carcinoma were assessed in vivo using cutaneous response and in vitro with a microlymphocyte blastogenic transformation (LBT) assay. In addition, correlation of the cutaneous response with the migration inhibitory factor (MIF) assay and LBT response was examined. The results indicated that cutaneous responses seen in patients with cancer of the lung were consistently lower than similar responses in normal controls (p less than 0.001). Similarily, the percentage of positive cutaneous responses seen with patients included in this study was lower than the frequencies reported by others. Stimulation of cells from lung cancer patients by PHA-M was also depressed when compared to similar lymphocytic responses in normal volunteers (p less than 0.001). The correlation between cutaneous response to tuberculin and the in vitro assays was high. The few instances of disparity demonstrate the need to utilize more than one assay in evaluating cellular immune functions. These data would support the work of others that indicate a depression of cellular immunity in advanced malignancy.

Evaluation of dye exclusion and colony inhibition techniques for detection of polyoma-specific, cell-mediated immunity.

Cellular immunity directed against polyoma virus-induced antigen was observed with C3H/HeJ splenic lymphoid cells from mice sensitized by a short-term immunization schedule with syngeneic polyoma 4198 and 4198V tumor cells. Polyoma specificity of the response was shown by demonstration that splenic cells from DBA/2J animals with polyoma virus-induced tumors were cytotoxic for the C3H 4198 and 4198V cells, but not for the L-M cell, another cell line of C3H origin. The polyoma-specific response in the syngeneic system was detectable with the dye exclusion assay but not with the colony inhibition procedure. Colony inhibition with the L-M cell was observed with sensitized lymphoid cells in both allogeneic and syngeneic systems.

Gastrin antibodies: induction, demonstration, and specificity.

Antibodies to the antral hormone gastrin have been induced in the rabbit and detected by passive hemagglutination. Specificity of the antibody, as determined by three methods, is directed to gastrins I and II, gastrin pentapeptide, and gastrin tetrapeptide, as well as to the stage-1 gastrin used for immunization.

Heterogenetic antigens of gram-positive bacteria.

Chorpenning, Frank W. (The Ohio State University, Columbus), and Matthew C. Dodd. Heterogenetic antigens of gram-positive bacteria. J. Bacteriol. 91:1440-1445. 1966.-Soluble antigens obtained by various methods from gram-positive bacteria were used to modify erythrocytes whose hemagglutinating reactions with immune rabbit sera and normal human sera were then studied. Antigens from all gram-positive organisms studied except corynbacteria altered red cells, causing them to react with specific bacterial antisera and with normal human sera; however, cross-absorption and inhibition tests indicated that at least three different specificites were involved. One of these antigens seemed to be similar to Rantz's streptococcal NSS, which is shared with Staphylococcus aureus and Bacillus spp., and is therefore heterogenetic. Another was found in streptococci but was apparently not present in S. aureus and Bacillus spp. A third antigen, also heterogenetic, appeared to be shared by several species of Bacillus and by S. aureus, but not by streptococci or any gram-negative bacteria. The third antigen was heat-stable at pH 8.0, and appeared to be essentially polysaccharide in nature. Normal human sera varied in their content of antibodies which reacted with erythrocytes modified by extracts from gram-positive bacteria. Whereas some sera reacted very broadly with red cells modified by extracts of practically any gram-positive organism, other sera agglutinated only cells which had been modified by streptococcal antigen.