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W Hicks

Publications and source records attributed to W Hicks.

At least 19 recordsLinked to original sources
PubMed2005

Alms1-disrupted mice recapitulate human Alström syndrome.

Mutations in the human ALMS1 gene cause Alström syndrome (AS), a progressive disease characterized by neurosensory deficits and by metabolic defects including childhood obesity, hyperinsulinemia and Type 2 diabetes. Other features that are more variable in expressivity include dilated cardiomyopathy, hypertriglyceridemia, hypercholesterolemia, scoliosis, developmental delay and pulmonary and urological dysfunctions. ALMS1 encodes a ubiquitously expressed protein of unknown function. To obtain an animal model in which the etiology of the observed pathologies could be further studied, we generated a mouse model using an Alms1 gene-trapped ES cell line. Alms1-/- mice develop features similar to patients with AS, including obesity, hypogonadism, hyperinsulinemia, retinal dysfunction and late-onset hearing loss. Insulin resistance and increased body weight are apparent between 8 and 12 weeks of age, with hyperglycemia manifesting at approximately 16 weeks of age. In addition, Alms1-/- mice have normal hearing until 8 months of age, after which they display abnormal auditory brainstem responses. Diminished cone ERG b-wave response is observed early, followed by the degeneration of photoreceptor cells. Electron microscopy revealed accumulation of intracellular vesicles in the inner segments of photoreceptors, whereas immunohistochemical analysis showed mislocalization of rhodopsin to the outer nuclear layer. These findings suggest that ALMS1 has a role in intracellular trafficking.

Animals↗
PubMed2005

Primary adenocarcinoma of cervical esophagus.

Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far.

Adenocarcinoma↗
PubMed2004

Human papilloma virus testing knowledge and attitudes among women attending colposcopy clinic with ASCUS/LGSIL pap smears.

OBJECTIVE: To study women's knowledge regarding the role of human papilloma virus (HPV) in cervical intraepithelial neoplasia and their attitudes toward the integration of HPV testing as part of routine follow-up of atypical squamous cell of uncertain significance/low-grade squamous intraepithelial lesion (ASCUS/LGSIL) abnormalities. METHODS: Over a 12-month period, all women attending the University of Ottawa colposcopy clinic for evaluation and follow-up of ASCUS/LGSIL Pap smears were recruited. Demographic data included age, nature of the Pap smear abnormality, gravidity, parity, occupation and education level, smoking history, previous history of abnormal smears, colposcopic examination and treatment, and current method of contraception. The women were asked to rate their level of concern over their Pap smear abnormality, from 0 (not concerned) to 10 (very concerned). Women's knowledge regarding the role of HPV in cervical intraepithelial neoplasia and the rationale behind the use of HPV testing was assessed by the clinic nurse as being minimal, moderate, or good, as defined by pre-specified criteria. Upon explanation by the nurses of the results of the recent ALTS (ASCUS/LGSIL Triage Study) trial, the women were asked to state whether they preferred to continue with regular colposcopic surveillance every 6 months, or to use the results of the HPV test, if negative, to reduce the number of colposcopy examinations to one annually. Descriptive statistics and logistic regression analysis were used to identify significant demographic factors associated with the women's preference for incorporation of HPV testing in their follow-up. All P values less than.10 were considered to be statistically significant, due to the exploratory nature of the study. RESULTS: Of the 100 women who participated in the study, 42% presented with ASCUS. The mean age (+/- SD) of the women was 33.63 +/- 11.25 years (range, 18-75 years); 66% were office workers with at least a community college degree, 86% reported previous abnormal Pap smears, and 67% had previously been seen for colposcopy. Fifty-eight percent of the women rated their concern level as being 6 or more, while 15% ranked their concerns as maximal at 10. In terms of knowledge about HPV, 75% of the women had no or very minimal knowledge of the role of HPV in cervical intraepithelial neoplasia. With regard to HPV testing, 84% of the study group had either never heard of the test or had only a minimal knowledge of HPV testing. After being informed of the ALTS results, 64% of the women chose to use HPV testing to help in triaging the needs for frequent colposcopy. Logistic regression modelling showed that a college level education (odds ratio [OR], 2.27; 95% confidence interval [CI], 0.95-;5.45; P =.06) and history of previous treatment for abnormal Pap smears (OR, 3.31; CI, 0.88- 12.46; P =.07) were closely associated with the adoption of HPV testing in clinical management. CONCLUSION: There exists a significant lack of knowledge about HPV and its role in the pathogenesis of cervical intraepithelial neoplasia. Women who have received previous treatments for cervical intraepithelial neoplasia and those with college-level educations were more likely to adopt this new technology as part of their care.

Adolescent↗
PubMed2001

Phosphate supplementation for hypophosphataemia and parenteral nutrition.

Routine detection and treatment of acute hypophosphataemia is important in intensive care unit and many other hospitalized patients, but metabolic bone disease and hypophosphataemia are still experienced as a result of parenteral nutrition. A significantly common problem that faces the compounding pharmacist when formulating parenteral nutrition regimens is the difficulty associated with the successful avoidance of calcium phosphate precipitation. Although incorporation of the normal calcium and phosphate requirements into regimens for metabolically stable adults is usually achievable, it can prove impossible in paediatric and neonatal mixtures when using the standard inorganic sources that are currently licensed for use in the UK and USA. In other countries, where organic compounds are routinely available, this problem does not exist.

Bone Diseases↗
PubMed1999

Does cartilage down-regulate growth factor expression in tracheal epithelium?

BACKGROUND: Maintaining tracheal integrity and restoring normal physiologic function after injury is complex. Some of the critical events in this process are deposition of a provisional extracellular matrix, tissue remodeling, and angiogenesis. These events are coordinated with epithelial migration and proliferation to restore the mucosal barrier. The ability of respiratory epithelial cells (REC) to migrate and proliferate and restore denuded areas of the large conducting airway after injury is poor. OBJECTIVE: To test the hypotheses that (1) the cartilaginous framework, underlying the extracellular matrix (submucosa) and epithelium, decreases the migratory ability of REC when compared with REC on the same provisional extracellular matrix (type I collagen) alone, and (2) this phenomenon is associated with a change in expression of transforming growth factor (TGF)-alpha and TGF-beta, both of which have been demonstrated in cutaneous models to be important in epithelial migration and proliferation. DESIGN: We developed a culture system that reconstitutes the tracheal lumen in vitro, consisting of dissociated chondrocytes cultured in a manner to form cartilage, submucosa (type I collagen), and REC (termed a "composite culture"). Control cultures consisted of epithelial cells grown on type I collagen alone. Control and composite cultures were evaluated morphologically using scanning electron and light microscopy. Expression of TGF-alpha and TGF-beta was determined in day 14 cultured epithelial cells from control and composite cultures by semiquantitative polymerase chain reaction. RESULTS: Epithelial cells from composite cultures did not spread and were less squamoid in morphological appearance than epithelial cells on type I collagen alone. Expression of both growth factors was reduced in epithelial cells from composite cultures compared with those on type I collagen. CONCLUSIONS: Cartilage modulates TGF-alpha and TGF-beta expression in REC, and may contribute to regulation of REC proliferation and differentiation.

Animals↗
PubMed1999

Ciliary activity in differentiating and reactivated human respiratory epithelial cells.

OBJECTIVE: Experimental studies of mucociliary clearance, especially those involving drug effects, suffer from the difficulty of determining whether drugs act directly on ciliary motility or whether their effects are indirect, acting via changes in cell metabolism, viscous load, or alternative mechanisms. The present study provides a solution to this problem by comparing the motile characteristics of ciliated cells that have differentiated in primary cell culture with those of demembranated cilia reactivated with MgATP. METHODS: Human respiratory epithelial cells (REC) were dissociated from trachea, bronchus, nasal polyps, or turbinates and then placed in a dissociated cell culture system. Thirty-three percent of the dissociated cells contain beating cilia. Following 1 week in culture, the REC dedifferentiated, but then redifferentiated within 96 hours after they were brought to an air interface. RESULTS: The cilia on such cells beat with planar waves consisting of power and recovery strokes. Beat frequencies at 20 degrees C were 15+/-2.3 Hz. Ciliary beating often was coordinated both within and between cells with a defined antilaeoplectic pattern of coordination. Either fresh or cultured cells could be demembranated with Triton X-100 and reactivated with MgATP. The activity of these reactivated models was equivalent to those observed in living cells. CONCLUSION: The authors have demonstrated that ciliary beat frequency of demembranated human respiratory epithelial cells can be modulated by MgATP and can be adjusted to the same level of activity as measured in living cells. This allows them to selectively test whether a drug's effects on mucociliary transport are the result of direct interactions with the ciliary apparatus or are produced through other indirect mechanisms.

Adenosine Triphosphate↗
PubMed1998

Respiratory syncytial virus and human bronchial epithelium.

BACKGROUND: A suitable model for respiratory syncytial virus (RSV) infection has yet to be developed. OBJECTIVE: To describe an in vitro model of human respiratory epithelium in primary cell culture linked with a computer microscope interface that allows evaluation and imaging of living RSV-infected respiratory epithelium. DESIGN: A descriptive, controlled study. Human bronchial cells were obtained from surgical samples by elastase dissociation and replated on collagen gel membranes. After 7 to 10 days, cells were brought to air interface. Baseline sampling of cell fluid for cytokine production by enzyme-linked immunosorbent assay (interleukin [IL] 1beta, IL-6, IL-8, and RANTES) and leukotriene C4 by radioimmunoassay was taken before treatment with RSV (n=30) or HEp-2 (human laryngeal carcinoma cells) control (n=25). Sampling was done at 4, 24, 72, and 120 hours thereafter. The infectious process was monitored with a microscope (Zeiss UEM, Carl Zeiss Inc, Thornwood, NY) equipped with a camera (Newvicon, Dage Corporation, Stamford, Conn). Images were either digitized using a computer (Macintosh Quadra 950, Apple Computers Inc, Cupertino, Calif) equipped with a digitizing board (Perceptics Corporation, Knoxville, Tenn) or were recorded on an SVHS videotape using a videocassette recorder (JVC, Elmwood Park, NJ). RESULTS: Respiratory syncytial virus induced profound effects on the ciliated cells: ciliostasis, clumping, and loss of cilia from live cells and sloughing of cells. Significant differences in the release of IL-6, IL-8, and RANTES (P<.03 for each cytokine) were noted in RSV-infected bronchial cultures by 24 hours with a peak at 72 hours. The IL-beta and leukotriene C4 were not altered by RSV infection in bronchial cells. CONCLUSIONS: This model closely mirrors human RSV disease and affords a unique opportunity to study interepithelial cell interactions, cytokine responses from cells of different donors, and ciliary activity of live cells undergoing RSV infection.

Bronchi↗
PubMed1997

Isolation and characterization of basal cells from human upper respiratory epithelium.

Cellular pathways of normal and reparative differentiation of upper airway epithelium are not well understood. Of the three main cell types, basal and secretory cells are known to divide, while ciliated cells are considered terminally differentiated. Several investigations support the role of the basal cell as a progenitor cell type, but others suggest that the secretory cell can regenerate a complete mucocilliary epithelium. Thus, lineage relationships within renewing adult epithelia are still unclear. Understanding the pathways involved in upper airway epithelial cell differentiation is critical for studying injury and repair mechanisms and for developing clinical strategies for tracheal reconstruction. We undertook the current studies to determine the integrin profile of isolated human upper airway basal cells. Respiratory epithelial cells (REC) were isolated by elastase digestion, stained with FITC-labeled Griffonia simplicifolia isolectin B4 (GSI-B4), and sorted by flow cytometry. Approximately 80% of the lectin-positive cells were basal cells, as determined by morphology and cytokeratin staining. These cells expressed integrins alpha 1, alpha 2, alpha 3, alpha 5, alpha v beta 5, beta 1, beta 3, and alpha 6 beta 4, by immunohistochemistry. This is the first report to identify the integrin profile of isolated human upper airway basal cells. These basal cells could be maintained on type I collagen for at least 7 days, where they became partially confluent and retained expression of cytokeratins 5 and 14. Availability of pure populations of basal cells should permit investigations of their role in both normal and maladaptive repair of adult upper airway epithelium.

Adult↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor as infection prophylaxis in high-risk oncologic surgery.

BACKGROUND: A method of augmenting host defenses against bacterial pathogens could result in a decrease in postoperative infections. Given its effects on leukocyte proliferation and function, it is possible that prophylactic granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce the incidence and severity of infections in high-risk surgical patients. The current study was undertaken to determine the safety and hematologic effects of perioperative GM-CSF. METHODS: Cancer patients undergoing operations with a high risk of postoperative infection were treated perioperatively for 10 days with subcutaneous GM-CSF. Cohorts were treated with GM-CSF at 125 micrograms/m2/day (12 patients) and 250 micrograms/m2/day (11 patients). RESULTS: There were no severe or life-threatening toxicities associated with GM-CSF. Mean maximum neutrophil counts during the first 5 postoperative days were 16.3 +/- 9.14 and 24.5 +/- 7.60 at 125 and 250 micrograms/m2, respectively (P = 0.04). Only one wound infection was diagnosed during this study. CONCLUSIONS: GM-CSF may be safely administered perioperatively at doses that augment neutrophil number and function. An ongoing randomized clinical trial will determine the impact of GM-CSF on postoperative infection.

Bacterial Infections↗
PubMed1995

Cytokeratin expression in human respiratory epithelium of nasal polyps and turbinates.

The cytokertatins in respiratory epithelial cells (REC) of human nasal polyps and turbinates were analyzed by immunohistochemistry. Cytokeratin 19 (CK19) was present in all REC, CK5 and 14 were expressed primarily in basal cells, and CK7, 8, and 18 were found in suprabasal cells. Differences in cytoplasmic locations were also apparent among the individual cytokeratins. CK13 was not detected in any REC of these tissues. The results indicate the profile of cytokeratins in REC of human nasal polyps and turbinates is essentially identical to that of REC in the more distal respiratory tract.

Antibodies, Monoclonal↗
PubMed1995

Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer.

An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.

Adenocarcinoma↗
PubMed1992

Results of surgical resection of pulmonary metastases of squamous cell carcinoma of the head and neck.

In this retrospective review of 58 patients (12 females and 46 males) with pulmonary metastases of squamous cell carcinoma of the head and neck treated between January 1, 1970, and December 31, 1989, we evaluated their clinical courses and analyzed the outcomes of those who underwent pulmonary resection. For the entire group of patients, factors predictive of survival in those patients with a diagnosis of pulmonary metastases included pulmonary resection of metastases (p = 0.0001), locoregional control of the head and neck primary tumor at the time of diagnosis of pulmonary metastases (p = 0.007), TNM stage of the head and neck primary tumor (p = 0.02), a single nodule seen on the chest radiograph (p = 0.02), and disease-free interval (DFI) from the primary tumor of the head and neck of 2 years or more (p = 0.05). Twenty-four of 58 patients underwent thoracotomy for resection of metastases. Four (17%) were found to have a second primary tumor of the lung. Of the 20 remaining patients who underwent explorative surgery for possible pulmonary resection, 18 (90%) underwent complete resection of all malignant disease with an estimated 5-year survival of 29%. In these patients, a DFI of less than 1 year was associated with a 5-year survival rate of 0%, whereas a DFI of 1 to 2 years was associated with a 5-year survival rate of 43% and a DFI of 2 years or longer had a 5-year survival rate of 33%. The number of malignant pulmonary nodules that were resected ranged from one to five and was not significant in predicting survival (p = 0.19). Of eight patients who underwent the resection of more than one malignant pulmonary nodule, 50% survived 2 years, but none survived 5 years. Resection of a solitary pulmonary metastasis from squamous cell carcinoma of the head and neck resulted in long-term survival in selected patients. Important prognostic factors included locoregional control of the head and neck primary tumor, the number of nodules seen on chest radiograph, the TNM stage of the primary tumor, and the DFI from the head and neck primary tumor. The value of resection in patients with more than one malignant pulmonary nodule remains to be defined for this group of patients.

Carcinoma, Squamous Cell↗
PubMed1989

Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms.

Twenty-seven patients with cutaneous and subcutaneous malignant neoplasms were treated with photodynamic therapy. Therapy was administered to 248 areas during a total of 72 separate treatment sessions after patients received a total of 45 injections of sensitizer. Seven patients had basal cell carcinoma, three had squamous cell carcinoma, three had malignant melanoma, one had liposarcoma, and 12 had breast cancers. One patient had Bowen's disease. Treatment was given either by surface radiation or interstitially. One month after treatment, 48 (67%) of the treatment sessions resulted in a complete response (no clinical evidence of tumor), and 19 (26%) resulted in a partial response (greater than 50% reduction in the number or size of tumors). Fifteen patients were examinable 12 months after treatment, and in this group, 31 treatment sessions were evaluated as a complete response one month after therapy, 15 (48%) of which retained this status at one year after treatment. By comparing the ability of different light-delivery instrumentation, it was concluded that the Yellow Springs radiometer (Yellow Springs Instruments, model 65A, Yellow Springs, Ohio) provided the most reliable spot power density readings. Straight-tipped fibers are nonhomogeneous and can result in overtreatment of the central area with necrosis and pain and in undertreatment of the periphery.

Humans↗
PubMed1984

Palliation of esophageal malignancy with photoradiation therapy.

Seven patients with severe or complete obstruction of the esophagus by malignancy were treated with photoradiation after presensitization of the tumor with intravenous hematoporphyrin derivative. The 625- to 635-nm therapeutic light was delivered from a tunable dye argon laser system coupled through quartz fibers, passed through the biopsy channel of a flexible esophagoscope, with local anesthesia. All tumors (adeno, squamous, and melanoma) responded, and swallowing was improved. Although tumor is still present, one patient is 11 months from initial treatment and is eating a regular diet. Another patient is 8 months from initial treatment and has no dysphagia. One patient died of aspiration of gastric tube feedings and 3 others died of their disease at 3 weeks, 3 months, and 6 months, respectively, from their initial treatment. Another patient died 11 months from his initial treatment due to a cardiac arrhythmia. During the 11 months after his initial treatment he continued to eat a regular diet.

Adenocarcinoma↗
PubMed1983

Hematoporphyrin-derivative and photoradiation therapy of malignant tumors.

Kodak projectors with #2418 red Corning filters were used as a light source to treat cutaneous and subcutaneous malignancies in five patients who previously had been given hematoporphyrin derivative (HpD). An argon dye laser system was used to treat malignancies in patients who also were given the HpD. These tumors included 11 melanomas of the eye, three carcinomas of the esophagus, one melanoma of the esophagus, four carcinomas of the lung, three basal cell skin cancers, and one retropharyngeal metastatic oral cancer. Clinical results and technical problems of this therapy are discussed.

Adenocarcinoma↗