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Biomedical subjects

J T Johnson

Publications and source records attributed to J T Johnson.

At least 127 records · Page 7Linked to original sources

In situ hybridisation for cytokine gene transcripts in the solid tumour microenvironment.

To determine if mononuclear cells (MNC) infiltrating various types of human solid tumours express genes for cytokines, in situ hybridisation with 35S-labelled cDNA antisense probes for interleukin 2 (IL2), interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL1-beta), transforming growth factor beta (TGF-beta) and interleukin 2-receptors (IL2R) was performed. Fresh-frozen tissue samples of ovarian carcinomas (n = 13), breast carcinomas (n = 12), and squamous cell carcinomas of the head and neck (SCCHN, n = 7) were evaluated for the presence and localization in the tumour of MNC positive for cytokine genes. In ovarian tumours and those breast carcinomas producing little or no mucin, only rare positive MNC were observed. In contrast, breast carcinomas producing mucin and all SCCHN contained numerous MNC expressing gene transcripts for IL2, IFN-gamma, TNF-alpha, IL2R as well as TGF-beta. In tumour-involved lymph nodes of patients with SCCHN, MNC expressing genes for cytokines were found around tumour metastases but not in non-involved areas. These data suggest that tumours expressing immunogenic antigens (e.g. mucin) contain many activated MNC, while other tumours either fail to activate or suppress functions of infiltrating MNC. In SCCHN or tumour-draining lymph nodes, local down-regulation of antitumour responses might be mediated by TGF-beta produced by activated tumour-infiltrating MNC.

Breast Neoplasms↗

Angiogenesis induced by head and neck squamous cell carcinoma xenografts in the chick embryo chorioallantoic membrane model.

The angiogenic potential of head and neck tumors compared to nonneoplastic control tissues was investigated by using the chick embryo chorioallantoic membrane (CAM) as a bioassay for angiogenesis. Eighty tumor specimens from 10 patients with squamous cell carcinoma of the head and neck were grafted onto the CAM of 7-day chick embryos. The presence of tumor in the original explant was confirmed histologically. Forty-four embryos (55%) survived and were evaluated histologically at day 17. Tumors were growing on or invading the CAM mesoderm in 30 of 44 embryos (68%). Before harvesting of the membranes, the tumors and surrounding blood vessels were photographed, and the angiogenic responses were graded by a panel of blinded observers. Tumor explants elicited a significantly greater angiogenic response than nontumor controls (p = .01). We conclude that head and neck squamous cell carcinomas can induce an angiogenic response in vivo, presumably secondary to the production of an unidentified angiogenic factor, and that the chick embryo CAM is an effective model for quantifying angiogenesis induced by head and neck tumors.

Allantois↗

Outcome of open surgical therapy for glottic carcinoma.

A retrospective review was undertaken of the medical records of 270 patients with carcinoma of the glottic larynx. Patients were staged pathologically, and clinical pathologic correlates were made with outcome. In 92 patients with early glottic cancer, the 2-year rate of no evidence of disease for T1 was 98%, and for T2, 84%. Vertical partial laryngectomy resulted in voice preservation in 89%. Patients treated for advanced (T3 or T4) glottic carcinoma underwent total laryngectomy with or without neck dissection. Cervical nodes were involved in 22% of T3 and 41% of T4 patients at the time of treatment. Survival with no evidence of disease was chiefly determined by the development of regional recurrence, distant metastasis, and new primary cancer. Distant metastasis was associated with extracapsular spread (p = .003). Patients treated for T4 glottic carcinoma with neck dissection had improved survival compared with patients treated with laryngectomy alone (p = .006). Improved survival must be aimed at regional control, prevention, and management of distant metastasis and new primary carcinoma.

Adult↗

Management of advanced cancers of the external nose.

Advanced carcinoma of the external nose is almost always associated with prior inadequate therapy. The first principle, therefore, in managing cutaneous malignancies of the nose is to achieve adequate tumor-free removal at the initial treatment. Recurrent carcinoma of the nose may require either hemirhinectomy or total rhinectomy to achieve tumor control.

Basal Cell Carcinoma↗

Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor in situ.

Several human head and neck squamous carcinoma cell lines were found to bind 125I-labeled or fluorescein-labeled interleukin 2 (IL-2). This binding was inhibited by an excess of cold ligand, IL-2, and by anti-p55 and anti-p70 monoclonal antibodies to the alpha and beta chains, respectively, of the IL-2 receptor (IL-2R). A small number (300/cell) of high-affinity IL-2R (2 x 10(-12) M) and a larger number (> 13,000/cells) of intermediate-affinity IL-2R (3 x 10(-10) M) were present on these tumor cells. By affinity cross-linking, tumor cells were shown to bind 125I-IL-2 to a M(r) 66,000 and 55,000 doublet peptide. The alpha and beta chains of the IL-2R also were detected on the surface of cultured tumor cells using the relevant monoclonal antibodies and flow cytometry. Immunoperoxidase staining with anti-p70 monoclonal antibody confirmed the expression of IL-2R on squamous cell carcinomas of the head and neck in situ. The presence of transcripts for p55/IL-2R-alpha and p70/IL-2R-beta in PCI-1 cells was confirmed by the polymerase chain reaction followed by hybridization to the IL-2R-alpha complementary DNA probe or IL-2R-beta complementary DNA probe, respectively. Our observations demonstrate that intermediate-affinity and high-affinity IL-2Rs are expressed on some human squamous cell carcinomas of the head and neck and that the receptors are functional, because growth of these tumor cell lines can be directly inhibited by exogenously supplied IL-2. The presence of IL-2R on human solid tumors could be important to consider, in addition to immunomodulatory effects of IL-2, in developing optimal therapeutic strategies for the administration of IL-2 to patients with cancer.

Antibodies, Monoclonal↗

Postoperative wound infection. A poor prognostic sign for patients with head and neck cancer.

BACKGROUND: The development of a wound infection has been identified as a favorable prognostic factor after oncologic surgical procedures. METHODS: The authors retrospectively studied the relationship between postoperative wound infection, local/regional tumor recurrence, and survival rates in 134 patients undergoing therapeutic surgical resection for squamous cell carcinoma of the head and neck (SCCHN). RESULTS: The median age was 61 years (range, 25-87 years) with most (75%) patients having advanced disease (Stage III or IV). Patients without evidence of recurrent disease were followed up for a median time of 34 months (range, 24-68 months). Twenty-nine (22%) had local or regional bacterial infections develop postoperatively. Recurrence rates were increased (P = 0.008) in patients with postoperative wound infections compared with patients who had distant infections, e.g., pneumonia or urinary tract infection, or no infection. Disease-free survival also was adversely affected (P = 0.04) in this group. Both advanced tumor stage and postoperative wound infections were independently associated with decreased survival, with odds ratios of 2:3 and 2:4, respectively. CONCLUSIONS: These data contrast with other reports in the literature of a beneficial effect of postoperative wound infection on outcome. These findings suggest a possible relationship between local/regional immune function and postoperative infection in patients with SCCHN:

Adult↗

Prophylactic antibiotics for head and neck surgery with flap reconstruction.

The leading cause of postoperative morbidity in patients undergoing major head and neck surgical procedures is postoperative infection. This prospective randomized multi-institutional clinical trial was designed to compare the effectiveness of clindamycin phosphate and high-dose cefazolin sodium therapy in preventing postoperative wound sepsis in patients undergoing contaminated head and neck surgical procedures in which flap reconstruction was required. Either clindamycin phosphate (900 mg) or cefazolin sodium (2 g) therapy was instituted intravenously prior to surgery and continued every 8 hours, for a total of 24 hours. The patients received postoperative follow-up, and the wounds were graded according to the worst condition observed. One hundred cases were evaluated. Fifty-one patients received clindamycin and 49 patients received high doses of cefazolin; wound infection developed in 10 patients (19.6%) and 11 patients (21.6%), respectively. This difference was not statistically significant. The average duration of surgery was approximately 8 hours for both the infected and the noninfected groups of patients. High-dose cefazolin and clindamycin have similar efficacy when administered prophylactically under these circumstances. Reconstruction with free vascularized tissue may aid in reducing postoperative wound infection.

Cefazolin↗

The lack of utility of a tumor marker panel in head and neck carcinoma. Squamous cell carcinoma antigen, carcinoembryonic antigen, lipid-associated sialic acid, and CA-125.

An ideal tumor marker should be sensitive in tumor-bearing patients while having adequate specificity so that controls do not demonstrate the marker. To date, a single circulating marker has not been identified for squamous cell carcinoma of the head and neck. This study evaluates a panel including squamous cell carcinoma radioimmunoassay, lipid-associated sialic acid, carcinoembryonic antigen, and CA-125. In this population of patients with cancer, serum samples from 101 patients and 88 controls were evaluated. The squamous cell carcinoma radioimmunoassay was the most sensitive marker identified (47.5%), while carcinoembryonic antigen level was elevated in 40.6%, lipid-associated sialic acid level in only 16.8%, and CA-125 level in 7.9%. False-positive results were found with all markers, including squamous cell carcinoma radioimmunoassay (18.2%), carcinoembryonic antigen (18.2%), lipid-associated sialic acid (10.2%), and CA-125 (15.9%). Various combinations of markers did not significantly improve either specificity or sensitivity. Available tumor markers are inadequate for diagnostic purposes in patients with squamous cell carcinoma of the head and neck.

Antigens, Neoplasm↗

Transmandibular approaches to the oral cavity and oropharynx. A functional assessment.

The records of patients undergoing transmandibular approaches to soft-tissue carcinoma of the oral cavity and oropharynx were reviewed retrospectively. Thirty-nine patients requiring lateral segmental hemimandibulectomy and 45 patients requiring a mandibulotomy were identified. None of the patients given mandibulectomy underwent bone reconstruction, while all of the patients with mandibulotomy had repair at the completion of the case. A total of 53 patients were available for recall and functional assessment. Patients with mandibulotomy did not experience significant dysfunction of the temporomandibular joint. Patients with mandibulectomy demonstrated increasing amounts of eccentric occlusion; however, this did not affect diet and was not reported to be uncomfortable by these patients. When feasible, preservation of the mandible yielded an improved aesthetic result; however, functional results in patients requiring mandibulectomy compare favorably with those obtained after mandibulotomy and repair.

Adolescent↗

Interleukin 2 receptors on squamous cell carcinomas of the head and neck. Characterization and functional role.

IL2Rs, in the presence of IL2, mediate activation and proliferation of human normal lymphocytes and modulate functional changes of some human leukocytic malignancies. IL2Rs have been demonstrated also on human neoplastic and fetal non-hematologic cells in vitro, although their functional role has not been described. We describe the presence of high affinity IL2Rs on squamous cell carcinoma of the head and neck (SCCHN) lines in vitro. Expression of 200 binding sites for IL2 with an affinity of 17 x 10(-12) was demonstrated by radiobinding experiments. When cytocentrifuged SCCHN cells were studied by immunoperoxidase staining, strong positive staining was repeatedly obtained using a monoclonal antibody to the p70 subunit of the IL2Rs. Experiments in vitro and in vivo, in a nude mouse model, showed a functional role for these receptors. In fact, low doses (8-500 U/ml) of IL2 were able to inhibit growth of 11 of the 16 SCCHN lines tested. Our observations may have broad implications for the immunotherapy of cancer in general, showing the complementary immunomodulatory and direct effects of IL2.

Carcinoma, Squamous Cell↗

Role of pulmonary phagocytes in host defense against group B streptococci in preterm versus term rabbit lung.

Intrapulmonary clearance of group B streptococci (GBS) occurred in term rabbits 4 and 8 h after infection; GBS growth was evident in preterm rabbits at 8 h. Bronchoalveolar lavage revealed 17-fold higher numbers of pulmonary alveolar macrophages (PAM) in term versus preterm animals immediately after infection, whereas polymorphonuclear leukocyte (PMNL) recruitment was 13-fold greater in preterm than term rabbits at 8 h. Anti-CD18 monoclonal antibody R15.7 did not reduce PMNL influx or GBS killing in term animals. R15.7 failed to inhibit PMNL influx but augmented GBS growth in preterm animals. R15.7 significantly impaired GBS phagocytosis by preterm and term PMNL in vitro but had no effect on ingestion of GBS by preterm and term PAM. Thus, GBS infection initiates PMNL recruitment into lungs of preterm rabbits by CD18-independent mechanisms, but phagocytosis of GBS by PMNL is largely CD18-dependent. The poorer outcome of GBS pneumonia in preterm versus term newborns may result from low levels of PAM, thereby mandating recruitment of PMNL as a second phagocytic defense.

Animals↗

Nasal cannula and transtracheal oxygen delivery. A comparison of patient response after 6 months of each technique.

The purpose of this study was to compare the efficacy of transtracheal (TT) oxygen delivery to that of nasal cannula delivery in subjects with chronic obstructive pulmonary disease (COPD). Twenty subjects (14 men, 6 women) were followed for 6 months during nasal cannula delivery. A TT catheter was then inserted, and measurements were repeated during TT use. With TT delivery, subjects required 45% less oxygen at rest and 39% less during exercise (p less than 0.0001). Oxygen use, measured by pounds of oxygen delivered to the home, also decreased, but the magnitude of change was less than anticipated (mean, 14%; range, +4% to -32%). Hospital days decreased from 12 +/- 10 during nasal cannula use to 4 +/- 6 during TT use (p less than 0.002). Exercise tolerance, as measured by a 12-min walk distance, was greater during TT use (p less than 0.0001). No change was seen in spirometry or acid-base balance. Also, no change was seen in Profile of Mood States, Sickness Impact Profile or Katz Adjustment Scale scores. Some problems were encountered relating to use of the catheter (displacement, mucus balls), but they were minor, and most were confined to the initial 2 months of TT use when the tract was immature. Our experience suggests that, in addition to decreasing oxygen flow rate, use of TT delivery may confer benefits that result in improved exercise tolerance and decreased hospitalization in patients with COPD.

Catheterization↗

Experimental tracheal replacement using a revascularized jejunal autograft with an implantable Dacron mesh tube.

Defects comprising more than 50% of the trachea cannot be reliably reconstructed by any current technique or prosthesis. A composite tracheal replacement implant consisting of a Dacron-urethane mesh tube and revascularized jejunal autograft was applied to this problem. This composite implant was used to replace 7 to 10 cm of trachea in eight dogs. The implant was sewn to the outside (serosal surface) of the jejunum to provide permanent structural support to the autograft, and an intraluminal silicone tube was placed inside the jejunal segment and left for 4 weeks following reconstruction. Six of eight animals survived the predetermined time periods and were killed painlessly in groups of two animals at 1, 2, and 6 months after removal of the intraluminal silicone tube. Postoperative intubation, ventilation, or tracheostomy was not necessary. Excessive secretions were not seen in any of the animals, and a fair to good performance status was maintained until death in all but one animal. Histologic examination revealed slight thinning of the jejunal mucosa, with no change in the jejunal muscularis. These data suggest that with further refinement this composite implant may be a viable reconstructive option in humans.

Animals↗

The efficacy of perioperative antibiotic therapy on recovery following tonsillectomy in adults: randomized double-blind placebo-controlled trial.

One hundred and one adult patients undergoing tonsillectomy for chronic/recurrent tonsillitis completed a prospective, randomized, double-blind, placebo-controlled study in which ticarcillin disodium and clavulanate potassium (Timentin) or placebo was administered intravenously at the time of surgery and for 12 hours postoperatively. The patients than received oral amoxicillin and clavulanate potassium (Augmentin) therapy or placebo for an additional seven days. Each patient kept a daily log to assess the incidence and severity of postoperative symptoms. Tonsillar core tissue at the time of surgery, as well as tonsillar fossa cultures after 7 days of treatment, were obtained. Those patients who received antibiotics fared consistently better in the immediate postoperative period compared with the placebo group. Specifically, patients in the antibiotic group experienced significantly less mouth odor, were able to tolerate a regular diet sooner, and resumed their normal activities earlier than did patients who received placebo. Patients who received antibiotics experienced fewer days with mouth odor (p = 0.004). In addition, on postoperative days 3 to 5, the antibiotic group was eating a regular diet (p = 0.05) and had returned to their routine activities earlier (p = 0.045) when compared with the placebo group. Perioperative antibiotic therapy was well tolerated and was effective in minimizing symptoms after tonsillectomy.

Adolescent↗

Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy.

PURPOSE: This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS: Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION: Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.

Adult↗

The suprahyoid approach for squamous cell carcinoma of the base of the tongue.

The suprahyoid pharyngotomy is a well-recognized surgical approach to the base of the tongue. However, its use has been widely criticized for squamous cell carcinomas. Some surgeons believe this approach offers limited exposure and that violating the preepiglottic space increases the risk of recurrence. A retrospective study of squamous cell carcinoma of the base of tongue was carried out to address these surgical concerns. Nineteen patients presented with T1 or T2 lesions, 13 of whom underwent suprahyoid pharyngotomy with neck dissection. Those with nodal disease underwent adjunctive irradiation therapy and those with extracapsular spread also received subsequent adjuvant chemotherapy. At present, all patients are disease free. The suprahyoid pharyngotomy is an ideal surgical approach in the management of T1 or T2 squamous cell carcinoma of the base of tongue.

Aged↗