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Biomedical subjects

J T Johnson

Publications and source records attributed to J T Johnson.

At least 145 records · Page 8Linked to original sources

Immunologic effector cells in head and neck cancer.

Freshly isolated tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in patients with head and neck cancer (HNC) often have low or undetectable functional responses. Because impaired ability of these cells to produce cytokines could be responsible for their functional incompetence, spontaneous and in vitro-induced production of interleukin-2 (IL2), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) by TIL, LNL from tumor-free as well as tumor-involved lymph nodes (LN), and peripheral blood lymphocytes (PBL) were measured. Although TIL or PBL of patients with HNC produced IL-1 beta and TNF-alpha spontaneously or after in vitro activation, LNL did not produce measurable levels of these cytokines. LNL also produced lower levels of IFN-gamma than PBL. In situ hybridization for cytokine mRNA performed with tumor tissues, and LN of patients with HNC showed that TIL as well as LNL localized in the immediate proximity of the tumor were activated, as evidenced by the expression of mRNA for IL2, IFN-gamma, IL-1 beta, TNF-alpha, and both alpha- and beta-chains of the IL2 receptor. In addition, many LNL located next to the tumor expressed mRNA for transforming growth factor-beta (TGF-beta). In contrast, LNL not adjacent to the tumor in involved LN, as well as those in tumor-uninvolved LN, did not express mRNA for cytokines or IL2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Abscesses and deep space infections of the head and neck.

Abscesses and deep space infections of the head and neck continue to be encountered in clinical practice. Recognition of these processes requires careful physical examination, an adequate index of suspicion, and appropriate application of modern imaging techniques. The principles of management of abscesses are largely unchanged. Space infections must be drained. A specimen should always be submitted for bacteriologic evaluation to allow change in antimicrobial administration when patterns of resistance are identified. Fungal infection should be considered when rhinosinusitis develops in the hospitalized immunocompromised patient. Biopsy of abnormal tissue is the mainstay of diagnosis under these circumstances. Therapy frequently requires surgical debridement in addition to administration of antifungal chemotherapy.

Abscess↗

Paranasal sinus carcinoma--diagnosis, treatment, and prognosis.

Sinonasal malignancies account for only 3% of all cancers of the head and neck and typically affect Caucasian males who are 50 to 70 years of age. This report identifies a number of risk and environmental factors that have been linked with the development of such malignancies, the clinical presentation of these tumors, clues to the diagnosis, and the pathology of the most commonly encountered types. Treatment of sinonasal malignancies is controversial and depends largely on the type of tumor encountered. The authors describe surgical and chemotherapeutic modalities, used alone and in combination. The controversy surrounding the utility of radiotherapy before or after surgery is also discussed.

Carcinoma↗

Microvascular free tissue transfer for reconstruction of head and neck cancer defects.

Over the last 10 years, microvascular free tissue transfer techniques have broadened the range of the head and neck surgeon, allowing for successful reconstruction of extensive curative extirpations in one operation with minimal morbidity. Success rates of more than 90% are now being achieved consistently. This article provides an overview of these revolutionary techniques for oral cavity, mandibular, and hypopharyngeal reconstructions. Patients are selected for microvascular free tissue transfer because of the large size of their defect, its location (eg, anterior mandibular loss), or complexity (circumferential defects of the hypopharynx). Others may be good candidates for this surgery because of previous radiotherapy or failed reconstructive surgery. Donor sites range from the radial forearm to the jejunum.

Follow-Up Studies↗

Enrichment in tumor-reactive CD8+ T-lymphocytes by positive selection from the blood and lymph nodes of patients with head and neck cancer.

To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8+ or CD4+ cells. The mean percentage of CD8+ cells captured on antibody-coated flasks from PBLs was 92% and that captured from lymph node lymphocytes (LNLs) was 98%. The initial enrichment in CD4+ T-cells was comparable. CD8+ T-lymphocytes captured from PBLs proliferated as well as unseparated lymphocytes in both patients with SCCHN and normal donors, while captured CD4+ PBLs of the patients showed significantly lower expansion than those of normal volunteers. Unseparated LNLs proliferated as well as PBLs, but captured CD4+ or CD8+ LNLs failed to proliferate in the presence of interleukin 2 (100 units/ml) and phytohemagglutinin (5 micrograms/ml). The addition to captured LNL cultures of irradiated autologous or allogeneic feeder cells significantly improved expansion of CD8+ LNLs but not CD4+ LNLs. During 15-day culture of captured CD8+ PBLs or CD8+ LNLs in the presence of feeder cells, a significant (P less than 0.05) enrichment in CD8+ T-cells was maintained [94 +/- 5% (mean +/- SEM) or 99.5 +/- 0.1%, respectively, on day 15]. Capture of CD8+ LNLs and their expansion resulted in the outgrowth of CD8+CD11b- effectors which had no or little cytotoxicity against Daudi, low cytotoxicity against K562, and very high levels of cytotoxicity against 4 different natural killer cell-resistant SCCHN targets, as measured in 4-h 51Cr release assays. Such significant enrichment in SCCHN-restricted cytotoxicity could be obtained with LNLs from tumor-uninvolved LNs but not from tumor-involved LNs. Captured and cultured CD4+ LNLs had no preferential anti-SCCHN cytotoxicity. The addition of irradiated autologous tumor cells to captured CD8+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CD8+ T-lymphocytes from tumor-uninvolved LNs of patients with SCCHN led to the enrichment in SCCHN-restricted but the major histocompatibility complex-unrestricted effector cells in 15-day cultures. Thus, CD8+ lymphocytes separated from tumor-draining LNs in patients with head and neck cancer contained cytolytic T-cell precursors capable of developing into effectors with preferential activity against SCCHN targets.

Aged↗

Induction of tumor regression in experimental model of human head and neck cancer by human A-LAK cells and IL-2.

In a nude mouse model of human squamous-cell carcinoma of the head and neck (SCCHN), locoregional therapy with interleukin 2 and human lymphokine-activated killer (LAK) cells resulted in a significant inhibition of growth of 3-day established tumors. The same model was used for therapy of 7-day established tumors with highly enriched populations of human adherent (A)-LAK (CD3- CD56+) cells and IL-2. Peritumoral transfer of 10 x 10(6) A-LAK cells, whose in vitro cytotoxicity against a SCCHN cell line (PCI-I) was not significantly different from that of LAK cells, resulted in complete regression of all 3-day or 7-day human SCCHN in nude mice. An initial inflammatory-type reaction, which appeared within hours of the first peritumoral cell transfer, was accompanied by infiltration initially by granulocytes and plasma cells, and later by mononuclear cells into the tumor stroma. A-LAK cells labelled with a fluorescent dye prior to injection appeared in the tumor stroma within 24 hr and were localized around or in the basal epithelial tumor layer by 48 hr. Histologic sections revealed an increasing epithelial disorganization and progressively decreasing basal epithelial layer, which were proportional to the increasing number of A-LAK cells transferred. Within 4 weeks, the tumors were reduced to amorphous keratinic remnants surrounded by the connective tissue containing abundant mononuclear cells. Local administration of human A-LAK cells and IL-2 to SCCHN tumors growing in nude mice led to accelerated tumor differentiation, keratinization and regression.

Animals↗

Role of prophylactic antibiotics in uncontaminated neck dissections.

The use of perioperative prophylactic antibiotics in uncontaminated head and neck surgery remains controversial. We performed a retrospective analysis of 192 patients undergoing uncontaminated neck dissections from 1976 to 1989. Wound infection developed in 10% (10/99) of patients who did not receive antibiotics, while only three (3.3%) of 93 patients who received antibiotics developed infections. This difference was not statistically significant. We correlated the use of flaps, length of surgery, prior radiation treatment, and postoperative complications with rate of wound infection. The difference was not statistically significant for any of these variables. Our beta error was, however, greater than 0.2. Our data do not demonstrate efficacy of prophylactic antibiotics in uncontaminated neck dissections with statistical significance; however, a trend exists suggesting its possible value.

Adult↗

Antiproliferative effects of cytokines on squamous cell carcinoma.

A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly.

Carcinoma, Squamous Cell↗

Functional and phenotypic analysis of lymphocytes in head and neck cancer.

We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.

Adult↗

The effect of postoperative radiation therapy on pharyngoesophageal reconstruction with free jejunal interposition.

Free tissue transfer of a jejunal segment was undertaken for laryngopharyngoesophageal reconstruction in 20 patients who received postoperative irradiation therapy. Treatment consisted of 1.8- to 2-Gy-fractions, the average total dose was 55.57 Gy (range, 40 to 66 Gy). Anastomotic strictures (six) were encountered early in the series and associated with stapled anastomoses. Hand-sewing the jejunoesophagostomy eliminated the problem. Enteric cutaneous fistula, bowel necrosis, and hemorrhagic enteritis were not observed. We conclude that the application of postoperative irradiation therapy to patients requiring jejunal interposition grafts is feasible.

Adolescent↗

Gene amplification and gene dosage in cell lines derived from squamous cell carcinoma of the head and neck.

Gene amplification and related alterations in gene dosage were analyzed in a series of 34 cell lines derived from different human head and neck squamous cell carcinomas (SCCHN). INT2 gene amplification was observed in 62%, MYC gene amplification in 24%, and EGFR gene amplification in 21% of the cell lines. There was a strong correlation between EGFR gene amplification and increased copies of the ERBB2 gene on chromosome 17, suggesting a synergistic selection for these two genes either during cancer progression or in culture. Two abnormalities showed a significant correlation with clinical course: MYC gene amplification showed an inverse correlation with tumor recurrence (r = -0.44, p = 0.01), and a small increase in MYCL gene copies on chromosome I correlated with the presence of metastases (r = 0.61, p = 0.001). This altered MYCL gene dosage might represent a chromosome translocation rather than true gene amplification. In addition to gene amplification, 79% of the cell lines had increased copies of chromosome 8. Comparison of the cell lines with several of the corresponding primary tumors demonstrated that most gene amplifications were already present in the primary tumors, although some appeared de novo in cell culture. These studies indicate that gene amplification, especially of INT2, is a prominent abnormality in head and neck squamous cell cancer. Aneuploidy and chromosomal lesions other than gene amplification were also found to alter the dosage of several oncogenes specifically.

Carcinoma, Squamous Cell↗

Concentrations of azithromycin in human tonsillar tissue.

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 micrograms/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 micrograms/g, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 micrograms/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.

Administration, Oral↗

Flow cytometric evaluation of adenoid cystic carcinoma: correlation with histologic subtype and survival.

Adenoid cystic carcinoma is an unusual but capricious tumor of salivary gland origin. Characteristically, these tumors follow a relentless clinical course, although some patients experience prolonged disease-free survival. Tumor size, site, and grade have been shown to correlate with tumor behavior. Recent investigation by others has suggested that DNA ploidy as determined by flow cytometry may provide an additional biologic marker of tumor behavior. This study was undertaken to investigate the relationship of DNA ploidy to tumor grade, biologic behavior, and patient outcome. A retrospective comparison of flow cytometric evaluations of paraffin-embedded formalin-fixed tumor specimens with patient outcome and histopathologic grade was undertaken. Follow-up of 4 to 7 years in 26 patients confirmed that the presence of a solid histologic component in the tumor correlated with the presence of recurrent or persistent disease (p = 0.04). Twenty-two of 28 tumors (78%) were found to be aneuploid on at least one section. Comparison of DNA ploidy with either patient outcome or the presence of a solid component did not achieve statistical significance, although a trend was suggested. This study confirms previous studies demonstrating the validity of histopathologic evaluation of tumor grade in the prediction of the biologic behavior of adenoid cystic carcinoma. However, our findings suggest that DNA ploidy has only limited value as an additional marker of tumor behavior in this patient population.

Carcinoma, Adenoid Cystic↗

Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized, double-blind trial, with pharmacokinetic implications.

Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome.

Cefonicid↗

Transtracheal delivery of oxygen: efficacy and safety for long-term continuous therapy.

Transtracheal (TT) oxygen delivery involves administration of oxygen percutaneously through a catheter inserted in the suprasternal trachea. Transtracheal oxygen delivery has been proposed as a means of overcoming the high visibility, inconvenience, and discomfort associated with nasal cannula use. This report describes our experience using TT delivery in 40 patients with chronic obstructive pulmonary disease (n = 32) and other types of lung disease (n = 8). Overall acceptance of TT catheter use was high and only 5 subjects elected to discontinue use. We believe the TT route is a relatively safe approach for oxygen administration and a promising method of improving patient compliance. It also offers the potential of more adequately oxygenating patients with refractory hypoxemia.

Adult↗

Carcinoma in situ and microinvasive squamous cell carcinoma of the vocal cords.

A retrospective study was undertaken to assess the outcome of 20 patients who underwent microlaryngoscopy and stripping of their vocal cord(s) with and without laser ablation of adjacent tissue for carcinoma in situ and/or microinvasive squamous cell carcinoma of the glottic larynx. Eighteen of 20 (90%) patients are currently free of disease following this course of treatment. The two treatment failures were in patients who had been lost to follow-up. A structured approach is presented to the clinical management of carcinoma in situ and microinvasive squamous cell carcinoma. We propose that the technique of tissue removal, microcup forceps stripping with or without laser ablation, is not the critical determinant of successful outcome, but rather that compulsive follow-up is most important to ultimate treatment success.

Carcinoma in Situ↗