Search PubMed⌕ Search

Biomedical subjects

J T Johnson

Publications and source records attributed to J T Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Determination of olanzapine in human breast milk by high-performance liquid chromatography with electrochemical detection.

A reversed-phase high-performance liquid chromatographic-electrochemical assay was developed and validated for the quantification of olanzapine in human breast milk. The assay involved a solid-phase extraction (SPE) of olanzapine and its internal standard on a Bond Elut Certify LRC mixed-mode cartridge. After conditioning of the SPE cartridge, human milk (1 ml) was passed through the cartridge. The cartridge was washed with five separate washing steps to remove endogenous compounds, and the analytes were eluted with ethyl acetate-ammonium hydroxide (98:2, v/v) solution. The eluate was evaporated to dryness (gentle stream of nitrogen at 40 degrees C), and the residue was dissolved in mobile phase. The extract was injected onto a YMC basic column (150 mmx4.6 mm I.D., 5 microm particle size) at a flow-rate of 1 ml/min. A mixture of 75 mM phosphate buffer, pH 7.0-acetonitrile-methanol (48:26:26, v/v/v) was used as the mobile phase. Standard curves with a lower limit of quantitation of 0.25 ng/ml of olanzapine were linear (r2> or =0.9992) over a range of 0.25-100 ng/ml. Based on the analysis of quality control (QC) samples, the average inter-day accuracy (RE) was 99.0% with an average precision (CV) of 6.64% over the entire range. The stability of olanzapine in human milk was established after three freeze-thaw-heat cycles and storage at -70 degrees C for 10 months. The validated method was used to measure olanzapine concentrations in human milk during a clinical trial.

Antipsychotic Agents↗
PubMed1999

The role of skull base surgery for the treatment of adenoid cystic carcinoma of the sinonasal tract.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the sinonasal tract is an aggressive malignancy associated with a poor 5-year survival rate. The role of skull base surgery for the treatment of patients presenting with sinonasal ACC and its impact upon their survival has not previously been evaluated. METHODS: A retrospective review of 35 patients with ACC of the sinonasal tract who were treated with surgery and radiation therapy at the University of Pittsburgh Medical Center was performed to evaluate patient outcome. RESULTS: Local recurrence of tumor following surgery and radiation therapy was observed in 36% of the patients originally treated at the University of Pittsburgh Medical Center. Fourteen percent of these patients developed a regional tumor recurrence, and 21% developed distant metastases. We did not identify any tumor-related factors that predicted patient outcome. Local recurrences were treated with salvage surgical excision, and, despite aggressive management, only 1 of 17 patients with local recurrence was considered cured (NED) at 24 months (follow-up after salvage surgery). Overall, disease-free survival was 46.4%, at a median follow-up of 40 months. CONCLUSIONS: ACC of the sinonasal tract is an aggressive malignancy. Skull base surgery has facilitated the gross total excision of advanced lesions that were deemed inoperable in the past, but has not resulted in an overall improvement in disease-free survival. Local recurrence portends a very poor prognosis, despite aggressive salvage regimens. Alternative therapies for local recurrences warrant further investigation. Prospective, randomized studies are necessary to evaluate the outcome of patients treated with aggressive multimodal treatment regimens, including chemotherapeutic regimens.

Adult↗
PubMed1999

Skin metastases from head and neck squamous cell carcinoma: incidence and impact.

BACKGROUND: Squamous cell carcinoma (SCC) of the upper aerodigestive tract rarely metastasizes to the skin. This study was designed to review the incidence of skin metastases, to identify associated risk factors, and to investigate the prognostic significance of skin metastases. METHODS: A cohort of 2491 patients treated for SCC originating in the upper aerodigestive tract were evaluated retrospectively. Patients who developed skin metastases were evaluated with respect to tumor stage, treatment, and outcome. Patients with skin metastases were compared with patients who developed distant metastases at other sites and with those who did not develop distant metastases. RESULTS: Skin metastases developed in 19 (0.763%) patients. The median time to occurrence was 6 months. Ninety percent of patients died of disease within a median of 3 months (1 to 16 months) following diagnosis. The development of skin metastasis is most closely related to the presence of two or more cervical metastases and/or extracapsular spread of tumor in the cervical metastases. Similar risk factors were identified for the development of distant metastases to other sites. CONCLUSION: Metastasis to skin is a rare occurrence which has prognostic significance similar to distant metastasis to other areas.

Carcinoma, Squamous Cell↗
PubMed1999

Detection of intracellular tumor necrosis factor alpha in stimulated fetal cells.

BACKGROUND: It is unknown if immature fetal cells produce tumor necrosis factor (TNF) alpha in the same manner that adult cells do. The aim of this study was to determine the feasibility of early detection of intracellular TNF produced by circulating human monocytes (Mo) and lymphocytes (Ly) using flow cytometry and to compare the stimulation profiles of mature and fetal cells. MATERIAL AND METHODS: Fetal umbilical cord blood (n = 10) and adult volunteer blood (n = 10) were obtained. In vitro stimulation with endotoxin (LPS) and ionomycin-PMA was performed. Brefeldin A was added to prevent extracellular transport of TNF. Cell type was determined by using CD-14 marker separating monocyte and lymphocyte populations. Anti-human TNF monoclonal antibody was used to detect intracellular TNF by flow cytometry analysis. RESULTS: Thirty to sixty thousand cells were analyzed per sample. Average TNF expression of stimulated fetal Mo was 28.2%, and that of fetal Ly was only 1.1%. Adult stimulated Ly had an average TNF expression of 31.9%, and adult Mo, 29.6% (P < 0.05 for adult Ly vs fetal Ly). CONCLUSION: TNF flow cytometry analysis allows assessment of individual cell types and their ability to produce that cytokine. Fetal cells are able to produce TNF when stimulated, but the stimulation profile of Ly differs from that of adult samples. This observation may be of clinical importance in evaluating the response of immature cells to a septic stimulus. Flow cytometry is reliable, reproducible, quick, and easily obtained from a small sample of peripheral blood. Clinical use will be applicable once appropriate controls are developed, as reported in this study.

Adult↗
PubMed1999

Squamous cell carcinoma of the sinonasal tract invading the orbit.

OBJECTIVE/HYPOTHESIS: The treatment of squamous cell carcinoma (SCC) of the sinonasal tract has evolved from routine exenteration of the orbital contents to sparing of the orbit when the SCC does not transgress the periorbita. Nonetheless, the influence of this change in treatment over the rate of local recurrence or survival has not been clearly elucidated. The objective was to ascertain whether orbital sparing surgery for the treatment of SCC of the paranasal sinuses influences the rate of local recurrence or survival. STUDY DESIGN: This is a retrospective study of patients presenting with SCC arising in the sinonasal tract, treated primarily at the University of Pittsburgh Medical Center from 1977 to 1990, including meta-analysis of the English literature regarding SCC of the sinonasal tract. METHODS: Review of medical records regarding demographics, histology, extension of tumor, pathologic results, type of surgery, adjunctive therapy, and outcome. Articles for meta-analysis were identified by Medline search and cross-referencing. RESULTS: Fifty-eight patients with orbital invasion, including bone and/or soft tissue invasion, were included in the study. Patients presenting with invasion of the bony orbit without soft tissue invasion were treated with maxillectomy and/or ethmoidectomy, sparing the orbital contents. Patients presenting with invasion of the orbital bones and soft tissues were treated with ethmoidectomy or maxillectomy, including orbital exenteration. At 3 years' follow-up, 52% of the patients whose orbit was exenterated were alive and without evidence of disease, compared with 59% of the patients whose orbit was spared. This difference was not statistically significant. Similarly, the rate of local recurrence was not statistically significant (P > .05). A meta-analysis of the literature revealed similar results. CONCLUSIONS: Our data suggest that sparing of the soft tissues of the orbit when the periorbita has not been transgressed by SCC does not downgrade the rate of cure or local control.

Carcinoma, Squamous Cell↗
PubMed1999

Allergic rhinitis and rhinosinusitis. Is there a connection between allergy and infection?

Each year allergic rhinitis and rhinosinusitis account for millions of office visits and billions of dollars spent on prescription and nonprescription drugs. Although the causes and symptoms of these two ailments differ, there is evidence that they are linked. The authors explain how effective control of allergy symptoms can reduce the incidence and severity of rhinosinusitis.

Bacterial Infections↗
PubMed1999

Clinical significance of decreased zeta chain expression in peripheral blood lymphocytes of patients with head and neck cancer.

Patients with squamous cell carcinoma of the head and neck (SCCHN) frequently have impaired immune responses. Alterations in T-cell receptor-associated signaling molecules in tumor-infiltrating as well as circulating lymphocytes have been reported in these patients. Using quantitative flow cytometry analysis, we have demonstrated that expression of the zeta chain is significantly decreased relative to normal controls in both CD8+ and CD4+ T cells as well as CD3- CD56+ CD16+ natural killer cells in the peripheral blood of patients with SCCHN who, as a result of previous therapies, have no evident disease. Patients with a more aggressive type of SCCHN and those who experienced a recurrence or had a second primary cancer within the last 2 years of the study had the lowest zeta chain expression. In addition, SCCHN patients showed a significantly greater spontaneous ex vivo apoptosis, as measured by a terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, in PBMCs, compared to normal controls. The observed decreased expression of zeta in T and natural killer cells coincided but did not directly correlate with significantly increased spontaneous apoptosis of lymphocytes obtained from treated patients with no evident disease. The results suggest that in patients with SCCHN, zeta chain defects and lymphocyte apoptosis are manifestations of long-lasting negative effects of tumor on the immune system.

Adult↗
PubMed1999

Spontaneous ex vivo apoptosis of peripheral blood mononuclear cells in patients with head and neck cancer.

Proportions of apoptotic (TUNEL+) peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry in patients with head and neck cancer and normal controls at the time of blood draws (0 time) and after 24-h incubation. PBMCs were incubated at 37 degrees C in medium (spontaneous apoptosis) and in the presence of CH-11 antibody (anti-Fas) or tumor necrosis factor (TNF)-alpha, both capable of inducing DNA fragmentation in activated T cells expressing the TNF family of receptors. PBMCs obtained from the patients had significantly higher (P < 0.0001) proportion of apoptotic cells than PBMCs of controls at 0 time as well as after 24-h incubation. Ex vivo apoptosis included all subsets of PBMCs: CD3+ T cells, CD16+ CD56+ natural killer cells, CD19+ B cells, and CD14+ monocytes, as determined by two-color flow cytometry. However, T cells represented the largest PBMC subset undergoing apoptosis, and lymphocytes rather than monocytes were the major TUNEL+ PBMC population. Among T cells, the level of spontaneous ex vivo apoptosis was nearly as high as that of CH-11 antibody-induced or TNF-alpha-induced apoptosis, indicating that activated Fas+ and TNFR1+ T cells were preprogrammed in vivo to die. Also, elevated levels of spontaneous apoptosis at time 0 in patients with head and neck cancer (P < 0.0001) indicated that a higher fraction of PBMCs was undergoing apoptosis in vivo in patients than controls. Together, the data suggest that an increased rate of turnover of lymphocytes is associated with cancer and may be responsible for functional lymphocyte imbalance, even in treated patients who have no evident disease.

Adult↗
PubMed1998

Perineural invasion in squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine if perineural invasion (PNI) of small nerves affects the outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract. DESIGN: Retrospective clinicopathological study of patients with at least 2 years of follow-up and with negative margins and no prior, synchronous, or metachronous SCC. SETTING: Academic otolaryngology department. PATIENTS: One hundred forty-two patients who had SCC of the oral cavity, oropharynx and hypopharynx, or larynx resected between 1981 and 1991. INTERVENTION: Surgery with or without adjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence was examined with respect to PNI, nerve diameter, and microvascular or microlymphatic invasion. Perineural invasion was correlated with lymph node metastasis, extracapsular spread, and survival. RESULTS: Perineural invasion of nerves less than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and vascular invasion in 9. Perineural invasion was significantly associated with local recurrence (23% for PNI vs 9% for no PNI; P=. 02), and disease-specific mortality (54% mortality for PNI vs 25% for no PNI; P<.001). With extralaryngeal tumors, PNI was associated with nodal metastasis (73% vs 46%; P=.03). Perineural invasion was not associated with extracapsular spread (P=.47). Microvascular invasion, lymphatic invasion, and nerve diameter were not significantly related to local recurrence. CONCLUSIONS: Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.

Carcinoma, Squamous Cell↗
PubMed1998

Lymphatic mapping with isosulfan blue dye in squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine whether intraoperative lymphatic mapping with isosulfan blue dye and sentinel lymph node biopsy accurately demonstrates the pathway of regional metastases from mucosal sites in squamous cell carcinoma of the head and neck. DESIGN: A prospective clinical study of intraoperative lymphatic mapping. SETTING: An academic tertiary referral center. PATIENTS: Patients with previously untreated squamous cell carcinoma of the head and neck whose surgical treatment included neck dissection. INTERVENTION: Injection of isosulfan blue dye into the mucosa surrounding squamous cell carcinomas of the upper aerodigestive tract during cervical lymphadenectomy. OUTCOME MEASURES: Correlation of the pathologic findings in the blue sentinel lymph node with those in the remaining cervical lymphatics. RESULTS: No blue-stained cervical lymphatics were identified after injection of the mucosa surrounding the primary squamous cell carcinoma with isosulfan dye. CONCLUSION: The technique of intraoperative lymphatic mapping with isosulfan blue dye requires further study before it can be used for the detection of occult cervical metastases in squamous cell carcinoma of the head and neck.

Adolescent↗
PubMed1998

Implications of cartilage invasion in surgically treated laryngeal carcinoma.

BACKGROUND: Cartilage invasion adversely affects the outcome of laryngeal carcinoma treated with radiotherapy. The UICC and American Joint Committee on Cancer (AJCC) classify laryngeal carcinoma with cartilage invasion as T4 or stage IV. METHODS: This study examines the prognostic significance of cartilage involvement in T3,4 N0,1 glottic carcinoma treated with total laryngectomy. Patients with tumor extension to pharynx, tongue, and thyroid gland, extracapsular spread, positive resection margins, and less than 2 years' follow-up were excluded. RESULTS: Sixty-seven pT3 (cartilage free of tumor) and 37 pT4 (cartilage invaded by tumor) cases were studied. The difference between the pT3 and pT4 groups in terms of local or regional recurrence, distant metastasis, and determinate survival was not significant. CONCLUSIONS: The results of this study question the use of cartilage invasion as a staging parameter for surgically treated laryngeal carcinoma. However, further studies with larger sample sizes are required to fully elucidate the prognostic significance, if any, of cartilage invasion in surgically treated cancer of the larynx.

Aged↗
PubMed1998

Preoperative, intraoperative, and postoperative management of patients with obstructive sleep apnea syndrome.

The patient with untreated, obstructive sleep apnea may present difficult or potentially life-threatening challenges to the surgical team. This is true even if the anticipated surgery is remote to the upper airway. Preoperative recognition of the obstructive apnea is essential as the first step in preventing potential complications. When recognized, intraoperative and postoperative initiative can result in a satisfactory outcome.

Cephalometry↗
PubMed1998

Mechanisms responsible for signaling and functional defects.

Lymphocytes recovered from human tumors or peripheral circulation of patients with advanced cancer have abnormalities in signaling via the T cell receptor (TcR) or Fc gamma RIII. Here we show that in comparison with normal T lymphocytes, those isolated from tumor-involved lymph nodes (LNLs) or blood (PBLs) of patients with head and neck carcinoma (HNC) have a variety of defects in expression and function of signaling molecules, including significantly decreased expression of TcR-associated zeta and epsilon chains, decreased Ca2+ flux, as well as impaired kinase activity following triggering with anti-CD3 antibodies and altered expression of downstream protein tyrosine kinase p56lck. Some of these alterations were demonstrable not only in isolated LNLs or PBLs but also in situ in patients' biopsies. Expression of mRNA for the zeta chain in LNLs was comparable with that seen in normal T cells. Significantly, LNLs of patients with HNC were shown to contain numerous apoptotic, TUNEL+ [TdT-mediated dUTP nick-enol labelling] cells in situ. Co-expression of CD3-epsilon+ and TUNEL+ in the same cells in situ was observed. Co-incubation of normal activated T cells or Jurkat cells with HNC cell lines induced apoptosis in a substantial proportion of lymphocytes. HNC cell lines and HNC in situ were shown to express FasL, while LNLs in tumor-involved lymph nodes were Fas+. These data suggest that signaling defects, which are commonly found in lymphocytes of HNC patients, might be a part of the process of apoptosis induced by the tumor in lymphocytes found in its milieu.

CD3 Complex↗
PubMed1998

Thyroid gland after total laryngectomy: CT appearance.

PURPOSE: To determine the computed tomographic (CT) appearance of the normal thyroid gland after total laryngectomy, because the high attenuation (or heterogeneous attenuation) of thyroid parenchyma was misinterpreted as tumor on several CT studies. MATERIALS AND METHODS: A search of computerized clinical files compiled from January 1996 through August 1997 yielded data on 24 patients who had undergone laryngectomy and subsequent CT of the neck. From these 24 patients, CT findings were available in 21. Because one patient had undergone total thyroidectomy and was excluded from the study, a retrospective review was performed in the remaining 20 patients. RESULTS: In 14 patients, unilateral thyroid tissue was present; in the other six there was bilateral thyroid tissue not connected by an isthmus. Thus, there were 26 remaining thyroid lobes, of which six were round and 20 were oval or lobular. Nineteen lobes showed homogeneously high attenuation (including one scanned without use of contrast material), six showed heterogeneous high attenuation or contained areas of hyperlucency, and one was obscured by streak artifact. CONCLUSION: Thyroid tissue can appear as unilateral or bilateral asymmetric masses on neck CT scans after laryngectomy. Gland tissue can show homogeneously or heterogeneously high attenuation. Familiarity with the varied postoperative appearance of normal thyroid gland can prevent its misdiagnosis as tumor.

Adult↗
PubMed1998

Endogenous IL-2 in cancer cells: a marker of cellular proliferation.

We have previously demonstrated that interleukin-2 (IL-2) receptors, IL-2 protein, and mRNA for IL-2 are present in human carcinomas in vitro and in vivo. Carcinoma cells synchronized in the G2/M-phase of the cell cycle express significantly more intracytoplasmic IL-2 as well as IL-2R-beta and -gamma than tumor cells in the G0/G1-phase. Here we evaluated immunohistologically the cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen and expression of the cytokine IL-2 in four different carcinoma cell lines. In addition, 34 tissue samples from patients with squamous cell carcinomas of the head and neck were simultaneously analyzed for Ki-67 and IL-2 expression and the data were correlated to the histological grade of the tumors. All tumor cell lines were shown to express IL-2 in the Golgi complex. The strongest IL-2 expression was seen in tumor cells undergoing mitosis, identified by double staining with the antibody to Ki-67. In the tumor tissue, the highest level of co-expression of IL-2 and Ki-67 was observed in poorly differentiated carcinomas, with a labeling index (LI) of 67. 2% for IL-2 and 68.8% for Ki-67. Well-differentiated carcinomas showed a significantly lower expression of both proteins (LI 35.0% for IL-2 and 26.5% for Ki-67). The correlation between the labeling indices was statistically significant (r = 0.747; p<0.001). These results demonstrate that IL-2 expression in human carcinoma tissues is strongly associated with cell proliferation and significantly correlates with the histological tumor grade.

Biomarkers, Tumor↗
PubMed1998

Gait and long cane kinematics: a comparison of sighted and visually impaired subjects.

Although visually impaired individuals have used the long cane to increase mobility for many years, few empirical studies have examined the effectiveness of this tool. The purposes of this research were to determine if these cane procedures provide adequate protection for visually impaired individuals and to compare sighted and visually impaired gait mechanics. Seven sighted (four females, three males) and five visually impaired subjects (two females, three males) were videotaped at 60 Hz by two cameras situated at opposite 45 degrees angles to the subjects' frontal plane so that three-dimensional coordinates could be calculated via direct linear transformation. One-way analyses of variance were calculated on 17 variables to determine if there was a significant biomechanical difference between sighted and visually impaired gait at an adjusted alpha = .003. The results showed that for both groups the cane tip touched outside where the foot landed and that the only variable significantly different between the two groups was resultant cane velocity. The major conclusion of this research was that present cane techniques may not provide adequate protection for visually impaired individuals since the purpose of mobility training is to have the person touch the ground with the cane tip at the foot contact positions.

Analysis of Variance↗