Biomedical subjects

B J Davidson

Publications and source records attributed to B J Davidson.

At least 19 recordsLinked to original sources

PubMed2001

Planned neck dissection for advanced primary head and neck malignancy treated with organ preservation therapy: disease control and survival outcomes.

BACKGROUND: The role of planned neck dissection after organ preservation therapy with radiotherapy or chemotherapy/radiotherapy for advanced head and neck cancers presenting with clinically positive neck disease is still being elucidated. The aim of this study is to review the outcomes of such patients treated by organ preservation therapy at our institution. METHODS: A retrospective chart review of 33 patients who underwent planned neck dissections after organ preservation therapy for advanced primary head and neck malignancy. Endpoints measured were disease-free survival and local, regional, and distant control. SETTING: Tertiary metropolitan medical center. RESULTS: Two-year actuarial disease-free survival was 61%, and neck control was 92%, with only two failures in the neck. The use of neoadjuvant chemotherapy and total dose of radiotherapy did not correlate with neck control or disease-free survival. The presence of pathologically positive nodal disease at the time of neck dissection did not correlate with recurrent neck disease, but was a predictor of local recurrence (p = .0086). CONCLUSIONS: Our data suggest that for patients undergoing planned neck dissection after organ preservation therapy, neck control is obtained in almost all cases. The presence of pathologically positive nodal disease at the time of surgery may have implications for the incidence of local recurrence.

Combined Modality Therapy↗

PubMed2001

Age and survival from squamous cell carcinoma of the oral tongue.

BACKGROUND: A worse outcome for young patients with head and neck squamous cell carcinoma has been previously suggested in the literature. This issue has been investigated with respect to squamous cell carcinoma of the oral tongue. METHODS: The Surveillance, Epidemiology and End Results (SEER) program tumor registries were used. Cases of squamous cell carcinoma of the oral tongue (ICD-9 codes 141.1-141.5) diagnosed from 1988-1993 in which this cancer was the one and only cancer were included (n = 749). Disease-specific survival was evaluated with respect to age, type of surgical treatment, and radiotherapy while stratifying for stage using Cox proportional hazards analysis. A secondary analysis included the additional variables, tumor size and nodal status. (These fields were recorded in SEER for only about half of the cases in the primary analysis.) RESULTS: Analysis revealed that increasing age predicted worse disease-specific survival. A 10-year increase in age was associated with an 18% increase in risk of death. Surgical therapy with excision of the primary tumor alone or excision plus neck dissection predicted improved survival, whereas the use of radiotherapy was associated with worse survival. (The latter may reflect bias associated with positive surgical margins or premorbid conditions.) In the secondary analysis, age, tumor size, and positive lymph node status were associated with significantly worse disease-specific survival, whereas surgical excision plus neck dissection was associated with improved survival. CONCLUSION: The SEER database shows increased disease-specific mortality with increasing age in patients with cancer of the oral tongue. Surgical therapy is associated with improved survival, whereas the use of radiotherapy, increasing tumor size, and positive lymph node status are associated with worse outcome.

Adult↗

PubMed2001

Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter review and an algorithm for airway management.

Angioedema is a nonpitting edema of which the presentation ranges from benign facial swelling to airway obstruction managed by intubation or tracheotomy. The presentation of this disease is reviewed, and a treatment algorithm based on initial signs and symptoms is proposed for proper airway management. We performed a retrospective review of 108 patients treated in 2 tertiary care centers in the Washington, DC, area over a 5-year period. Ninety-eight patients (90.7%) were African-American, and 81 (75%) were female. Seventy-four patients (68.5%) were taking angiotensin-converting enzyme inhibitors (ACEIs). A classification system was developed based on the location of the edema at initial presentation: 1) isolated facial swelling and oral cavity edema, excluding the floor of the mouth; 2) floor of mouth and/or oropharyngeal edema, and 3) oropharyngeal edema with glottic and/or supraglottic involvement. Fourteen patients (13%) needed airway intervention, 2 of whom underwent a cricothyrotomy after a failed intubation attempt. Eleven (78.6%) were taking ACEIs. The indication for each intubation was massive tongue and floor of mouth edema. The patients were extubated 48 to 72 hours later. No patient demonstrated symptom progression after medical treatment was initiated. Therapy included discontinuation of the ACEI or other inciting agent, a high-humidity face tent, an initial dose of intravenous antihistamines, and a continued course of intravenous steroids. Within 48 hours, most patients had a resolution of their edema. Only cases of significant tongue and oropharyngeal edema took longer than 48 hours to resolve. The ACEIs are a common cause of angioedema. Left untreated, angioedema may progress to involve the oropharynx and supraglottis, resulting in a life-threatening airway compromise. Marked floor of mouth and tongue edema are the indications for airway intervention. An algorithm based on the initial presentation is essential for proper airway and patient management. Once treatment has begun, angioedema is nonprogressive and often resolves within 24 to 48 hours.

Adult↗

PubMed1999

Complications from planned, posttreatment neck dissections.

OBJECTIVE: To report the complication rate from planned, posttreatment neck dissections in patients who show control of primary squamous cell carcinoma by chemotherapy and radiotherapy or radiotherapy alone. DESIGN: Retrospective review of case series. SETTING: Georgetown University Medical Center, Washington, DC. PATIENTS: Thirty-four patients with clinically positive neck disease treated with organ preservation therapy for squamous cell carcinoma of the head and neck. INTERVENTIONS: Planned neck dissection after treatment with chemotherapy and radiotherapy or radiotherapy alone. MAIN OUTCOME MEASURE: Perioperative complications. RESULTS: Forty-one neck dissections were performed on 34 patients. Complications were seen in 13 (38%) of 34 patients and 15 (37%) of 41 neck dissections. Wound complications occurred in 9 (22%) of 41 dissections. Neck dissection complication rate did not correlate with previous use of chemotherapy or with the use of brachytherapy at the primary site at the time of the neck dissection. Preoperative radiotherapy dose greater than 70 Gy was associated with complications in 58% vs 29% when preoperative dose was less than 70 Gy (P = .09). This trend was reflected primarily in wound complications (42% vs 14%; P = . 10) and reached significance for skin flap necrosis (33% vs 0%; P = .005). Other factors that were associated with increased complications were preoperative albumin level less than 38 g/L and early neck drain removal. CONCLUSIONS: The complication rate associated with planned posttreatment neck dissection is similar to that previously reported for neck dissection. Wound complications are more common when higher preoperative radiotherapy doses are used.

Carcinoma, Squamous Cell↗

PubMed1998

9p21 deletion correlates with recurrence in head and neck cancer.

BACKGROUND: Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC. METHODS: We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis. RESULTS: We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2. CONCLUSIONS: These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence.

Aged↗

PubMed1996

Supraspinal accessory lymph node metastases in supraomohyoid neck dissection.

BACKGROUND: Some patients undergoing surgical resection of primary squamous cell carcinoma of the oral cavity and oropharynx also undergo supraomohyoid neck dissection for staging of the negative (N(o)) neck. Dissection of the supraspinal accessory lymph node pad requires significant traction of the spinal accessory nerve. There are currently no data to indicate the incidence of metastases to this site and thus the necessity of performing dissection of these nodes. METHODS: A prospective analysis of a consecutive series of 44 patients with newly diagnosed squamous carcinoma of the oral cavity or oropharynx undergoing surgical management of the primary lesion with staging neck dissection was performed. Patients underwent unilateral (41) or bilateral (3) supraomohyoid neck dissection with separate submission of the supraspinal accessory lymph node pad for pathologic evaluation to determine the incidence of nodal metastases. RESULTS: A total of 15 patients (32%) had microscopic metastatic squamous cell carcinoma involving the supraomohyoid neck dissection specimen. Only 1 patient had a metastatic deposit involving the supraspinal accessory lymph node pad. This patient also had metastases in additional lymph nodes at level II. There was an equal incidence of metastases for all patients when stratifying by T stage. CONCLUSION: This preliminary report reveals a small incidence of supraspinal accessory lymph node metastases in patients with T + NO squamous cell carcinoma of the oral cavity and oropharynx. We continue to accrue patients to determine if the incidence of supraspinal accessory lymph node metastases varies with an increased number of patients.

Adolescent↗

PubMed1996

Long-term effects of botulinum toxin injections in spasmodic dysphonia.

The purpose was to examine whether physiological changes can be found in laryngeal muscles following repeated treatment with botulinum toxin injections in spasmodic dysphonia. Seven patients whose treatment consisted of multiple unilateral thyroarytenoid injections were examined more than 6 months following their most recent botulinum toxin injection fiberoptic laryngoscopy and electromyography. Comparisons were made between injected and contralateral noninjected muscles' motor unit characteristics, muscle activation patterns, and vocal fold movement characteristics. The results demonstrated that motor unit characteristics differed between injected and noninjected muscles and that these differences were greater in patients less than 12 months since last injection. Motor unit duration differences were reduced and motor unit amplitude and numbers of turns were increased in muscles sampled over 1 year after injection. These results suggest that while the physiologic effects of botulinum toxin are reversible, the reinnervation process continues past 12 months following injection.

Adult↗

PubMed1995

Homozygous deletions and loss of expression of the CDKN2 gene occur frequently in head and neck squamous cell carcinoma cell lines but infrequently in primary tumors.

Deletion of 9p21-22 is a common genetic alteration in dysplastic, in situ, and invasive head and neck squamous cell carcinoma (HNSCC). However, a candidate tumor suppressor gene (TSG) at this site has thus far not been identified in HNSCC. We report homozygous deletion of the recently identified multiple tumor suppressor I (MTSI)/cyclin-dependent kinase-4-inhibitor (CDKN2) gene mapped to 9p21, which encodes the p16 protein, a regulator of cyclin-dependent kinase 4, in six of 16 HNSCC cell lines. We also show absence of the CDKN2 mRNA in all cell lines with CDKN2 deletion as well as in an additional two cell lines without deletion. Overall, we have identified 9p abnormalities in 12 of 16 (75%) cell lines, at least nine of which involved CDKN2. We further demonstrate that the CDKN2 deletion in HNSCC is located within a previously described region of allelic loss between D9S171 and IFNW, which spans a 4 cM region of 9p. However, examination of 36 primary tumors revealed genetic alterations in only seven of 36 (19%) tumors. These results suggest that genetic alterations at CDKN2 are frequent in HNSCC cell lines, but the role of this gene in primary tumors is less compelling. CDKN2 does not appear to be the only TSG on 9p21 in HNSCC, and our results suggest that another region of deletion exists proximal to the IFNW locus.

Carcinoma, Squamous Cell↗

PubMed1994

TP53 gene mutations and CCND1 gene amplification in head and neck squamous cell carcinoma cell lines.

Mutations of the tumor-suppressor gene TP53 and amplification of CCND1 gene have been reported to occur frequently in head and neck squamous cell carcinomas (HNSQCC). In experimental systems, TP53 mutations have been shown to lead to genomic instability, including an increased propensity for gene amplification. We have examined 16 HNSQCC cell lines for the association between TP53 over-expression/mutation and CCND1 amplification. p53 over-expression was detected in 50% of the cell lines by immunohistochemistry using the monoclonal antibody (MAb) PAb1801. TP53 mutations were also detected in 50% of the cell lines by analysis of single-strand conformation polymorphism (SSCP) and DNA sequencing of exons 4 through 9. Six cell lines showed TP53 mutations and over-expression of the protein, 2 cell lines showed TP53 mutations but no p53 expression, and 2 cell lines showed over-expression of p53 protein but no TP53 gene mutations. CCND1 amplification was found in 38% of the cell lines by Southern blot analysis. Only 1 cell line showed both TP53 mutation and CCND1 amplification, whereas 7 of 8 cell lines with TP53 mutations had no CCND1 amplification. pRb expression was detected by Western blot analysis, and the level of pRb did not correlate with either CCND1 amplification or TP53 mutation. Our findings suggest that TP53 mutation and CCND1 amplification are common genetic alterations in HNSQCC and that the occurrence of either genetic event may be sufficient to abrogate normal cell cycle control.

Carcinoma, Squamous Cell↗

PubMed1994

Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines.

Factors controlling glutathione metabolism may govern sensitivity to chemotherapeutic agents such as cisplatin. Using a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas, we examined cisplatin resistance relative to (a) glutathione-S-transferase (GST)-pi gene amplification and expression, (b) basal and inducible GST-total and GST-pi enzymatic activity, and (c) cellular levels of reduced glutathione (GSH). Using Southern blot analysis and northern blot hybridization, no relationship between GST-pi gene amplification, mRNA expression and drug resistance could be identified. Despite the capacity of cisplatin to induce GST enzyme activity, the response was variable and unrelated to cisplatin responsiveness. However, an inverse relationship between GSH levels and cisplatin sensitivity was identified. To further clarify these effects, cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum), which altered cellular GSH in a biphasic manner. Pretreatment with SAC to lower cellular GSH levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth.

Carcinoma, Squamous Cell↗

PubMed1994

Cervical metastases of occult origin: the impact of combined modality therapy.

BACKGROUND: We have updated our experience with metastatic carcinoma to the neck of occult origin to assess whether increasing use of adjunctive radiation therapy has had a significant impact. METHODS: This retrospective review of 115 patients treated between 1977 and 1990 includes 73 (63%) with squamous cell carcinoma. These 73 patients were analyzed for survival, control of disease in the neck, and incidence of subsequent primary tumors. RESULTS: There has been no change in the proportion of patients with advanced neck disease (N2/N3 = 52; 71%) when compared to our last report. Surgery included comprehensive neck dissection in 59 (81%) and adjunctive radiotherapy was employed in 54 (83% of surgically treated patients). Primary carcinomas within the head and neck were identified subsequently in 9 (12%) patients, including 4 of 11 (36%) who did not have adjunctive radiotherapy and 5 of 54 (9%) who did (P = 0.038). Control of the treated neck (54/73; 74%) has improved significantly (P = 0.005) when compared to our earlier experience (37/74; 50%), and this was most apparent in those with extensive neck disease. However, cumulative survival at 5 years (45%) was not significantly different from that previously reported. CONCLUSION: Our data support the increased use of adjunctive radiation therapy for metastatic squamous cell carcinoma in the neck of occult origin. Control of neck disease has improved and the likelihood that a primary will be identified has been reduced, but there has been no improvement in survival when compared to historical controls.

Adult↗

PubMed1994

The relationship of loss of heterozygosity to tobacco exposure and early recurrence in head and neck squamous cell carcinoma.

BACKGROUND: Tobacco usage contributes to carcinomas of the lung, bladder, esophagus, uterine cervix, and head and neck, and can induce specific genetic lesions. Studies of the above tumor types have documented allelic deletions affecting 3p, 5q, 9p, 9q, 10q, 11p, 13q, 17p, and 18q. Relationships between genetic loss, tobacco exposure, and patient outcome have not been described. PATIENTS AND METHODS: To confirm and further define loss of heterozygosity in head and neck squamous cell carcinoma (HNSCC), and to examine relationships between loss of heterozygosity and both tobacco exposure and early recurrence, we undertook this study on previously untreated patients with HNSCC. We performed a Southern blot analysis using 11 probes specific for loci deleted in tobacco-associated cancers. We have investigated 42 prospectively collected, paired samples of HNSCC and peripheral blood. Demographic and follow-up data were collected on these patients. RESULTS: Significant loss of heterozygosity was observed in descending order of frequency at 11p, 9p, 17p, 3p, 10q, and 13q. All nonsmokers showed loss of heterozygosity on one or more loci compared with only 53% of smokers (P < 0.05). Furthermore, patients with multiple deletions had a significantly higher rate of early recurrence than those with fewer deletions (P < 0.05). CONCLUSION: Multiple deletions occurred more frequently in nonsmokers and predicted a higher risk of early recurrence.

Blotting, Southern↗

PubMed1993

The genetics of tobacco-induced malignancy.

OBJECTIVE: Several areas of investigation contribute to an increasing understanding of the genetics of malignancies associated with tobacco use. While the strong influence of tobacco exposure on cancer development obscures genetic influences, there are indications that aspects of cancer susceptibility may have a heritable basis. In addition, specific sites within the genome appear to be commonly involved in these malignancies. This review describes research relevant to investigation of the genetics of tobacco-induced malignancy. DATA SOURCES: A review of the pertinent literature covered the past 20 years. References were gleaned from a variety of sources including manual review of the most recent journals, a computerized database (Mini-MEDLINE), references cited in previous works, and our own ongoing research in cancer genetics and molecular biology. STUDY SELECTION AND DATA EXTRACTION: Whenever possible, controlled studies from peer-reviewed journals were used. Where studies have shown conflicting results, the possible confounding factors are discussed. DATA SYNTHESIS: From a broad array of research areas, a view of the genetic aspects of tobacco carcinogenesis emerges. This includes syndromic and nonsyndromic susceptibility, genetic determinants of carcinogen metabolism, DNA adduct formation, and site-specific genetic alterations in tobacco-induced malignancy. In addition to specific gene alterations commonly seen in tobacco-induced malignancy, viral infections may contribute to cancer development through pathways related to tobacco carcinogenesis. CONCLUSION: Further research on many aspects of tobacco-induced carcinogenesis is warranted. Investigation of cancer susceptibility may contribute to understanding DNA surveillance and repair pathways. Carcinogen metabolism investigations have application in cancer detection and prevention schemes. Further understanding of tumor suppressor gene function and the role of gene amplification in carcinogenesis may allow design of gene-specific strategies in cancer treatment.

Carcinogens↗

PubMed1993

Posterior triangle metastases of squamous cell carcinoma of the upper aerodigestive tract.

The trend toward function-conserving surgery in the treatment of squamous cell carcinoma of the head and neck has led to a progression from radical neck dissection to modified neck dissection and selective neck dissection has growing support. These surgical modifications have resulted from an effort to spare structures uninvolved with malignancy. Level V dissection can be associated with spinal accessory dysfunction in some patients even when the nerve remains intact. In this study, we have attempted to address the need for level V dissection by determining the prevalence of level V metastases in a large series of patients undergoing radical neck dissection. There were 1,123 patients who underwent 1,277 neck dissections between 1965 and 1986. A review of pathologic and clinical records revealed 40 patients (3%) with positive nodes at level V. The prevalence of level V metastases was greatest with hypopharynx and oropharynx primary tumors (7% and 6%, respectively). Level V metastases were found in 1% of patients with oral cancers and 2% of those with larynx cancers. Groups were divided into N0 (282), N+ (719), and subsequent N+ (276), depending on the clinical status at the time of surgery. Thirty-seven of 40 patients with posterior triangle metastases were clinically N+. The prevalence of metastases at level V was 1% for N0, 5% for N+, and 0% for subsequent N+. This large series shows minimal involvement of metastases at level V. The low likelihood of metastases at level V, even in N+ disease, should be considered when performing lymphadenectomy for squamous cell carcinoma of the upper aerodigestive tract.

Carcinoma, Squamous Cell↗

PubMed1993

Thyroid cancer.

Management of thyroid cancer varies somewhat between communities and institutions depending on tumor type and individual treatment philosophy. The differentiated thyroid cancers have a significantly better outlook than the medullary and anaplastic. This article provides an overview of the literature that describes pathogenesis, diagnosis, and treatment currently recommended for these thyroid cancers.

Humans↗

PubMed1992

Sperm hyperactivation as quality control for sperm penetration assay.

The sperm penetration assay (SPA) is subject to considerable variation, and controls are needed to verify the accuracy of the results. It is proposed that sperm hyperactivation (HA) can serve as a quality control check for the SPA. The objective was to determine if there was an association between the SPA outcome and sperm HA measured at various times during the SPA procedure. The data showed a significant correlation between percent sperm HA and percent zona-free oocyte penetration by sperm preincubated for three hours prior to sperm-oocyte interaction (short preincubation). Some sperm hyperactivity was observed in liquefied raw semen samples, but this was insignificantly related to SPA results. Low correlation was observed between SPA results and sperm HA determined immediately after centrifuge washing of sperm. The results suggest that it is possible to utilize sperm HA measured immediately after the sperm-oocyte interaction period as a quality control check of SPA results.

Female↗

PubMed1992

The perforated tympanic membrane.

Tympanic membrane perforations typically result from trauma or acute otitis media. Most perforations do not cause more than a mild conductive hearing loss, aural fullness and mild tinnitus. Blood, purulent secretions and other debris should be carefully suctioned out of the canal and the perforation size and location described. Irrigation and pneumatic otoscopy should be avoided. A history of vertigo, nausea and vomiting and an audiogram showing a conductive hearing loss of more than 30 dB suggest disruption of the ossicular chain. Profound sensorineural loss may signify inner ear nerve damage. Mastoid radiographs and computed tomographic scans may be useful in cases of significant trauma and infection. Most small perforations resolve spontaneously. The affected ear should be kept dry. Oral and topical antibiotics may be prescribed for perforations related to acute otitis media. Otolaryngologic referral may be necessary to evaluate traumatic perforations associated with vertigo or significant hearing loss, perforations from chronic otitis media or perforations from acute otitis media that do not heal within one month.

Ear Diseases↗

PubMed1990

ABO blood group differences in bone mineral density of recovering alcoholic males.

Since ABO blood group differences are associated with varying responses to many diseases, ABO blood type and bone density were studied in 39 recovering male alcoholics, comparing those with blood type O and non-O. The type O subjects had significantly higher bone densities as measured by quantitative computed tomography of the vertebrae than the non-O subjects (175.4 +/- 8.5 and 140.7 +/- 7.6, respectively, p = 0.004). There were no differences in age and indices of their alcoholism. Using multiple stepwise regression analysis, neither race nor maximal amount of alcohol consumed appeared to contribute to the differences in bone density. Only age, number of years of regular alcohol use and ABO blood type were determinants of the bone density differences. The ABO blood type contributed 20.3% to the differences in bone density (p = 0.001). The patients with non-O blood type lost a significant amount of bone with advancing age (r = -0.76, p = 0.0001) while those with blood type O did not (r = -0.37, p = 0.11). We conclude that, although alcoholism is a factor in the development of osteopenia, in males the ABO blood group status plays a significant role in the maximal mineralization of the skeleton and the amount of bone resorption during ageing, independent of alcohol abuse.

ABO Blood-Group System↗