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Biomedical subjects

P J Donald

Publications and source records attributed to P J Donald.

At least 19 recordsLinked to original sources

Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.

Antibody Specificity↗

Sphenoid marsupialization for chronic sphenoidal sinusitis.

OBJECTIVES: To review experience with sphenoid marsupialization and describe the technique using new instrumentation. STUDY DESIGN: Retrospective review of five cases of chronic sphenoid sinusitis that were resistant to standard medical and surgical methods, which were treated by sphenoid marsupialization. METHODS: Charts were reviewed and patients were interviewed regarding postoperative resolution of symptoms. RESULTS: Five cases of recalcitrant sphenoid sinusitis were reviewed. All patients had headache before surgery, and two had visual disturbance. In follow-up ranging from 1 to 87 months, all were free of symptoms related to the sphenoid sinus. CONCLUSIONS: Marsupialization is an effective method of exteriorizing a chronically infected sphenoid sinus. The use of functional endoscopic sinus surgery instruments and the TAC attachment of the Midas Rex drill make this surgery possible.

Adult↗

Predictive value of cathepsin-D for cervical lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Prognosis of head and neck squamous cell carcinoma (HNSCC) is strongly associated with cervical lymph node metastasis. Cathepsin-D is a lysosomal protease expressed in all cells. Its role in extracellular matrix degradation is postulated to promote tumor invasion and metastasis. Increased cathepsin-D has been demonstrated in cervical lymph node metastasis in HNSCC. METHODS: Formalin fixed tumor biopsy samples from 34 patients with HNSCC of the oral cavity, oropharynx, or hypopharynx were analyzed for the presence of cathepsin-D by immunohistochemistry (1:8000, Calbiochem, Cambridge, MA). Tumors were considered positive if >50% of cells showed strong cytoplasmic staining. RESULTS: All patients had T1 or T2 lesions ranging in size from 1-4 cm and 19 (56%) had cervical metastasis. Eight (24%) were well differentiated and 26 (76%) were moderately or poorly differentiated. Thirteen tumors (38%) had high cathepsin-D expression that was strongly associated with cervical lymph node metastasis (p = 0.008). When adjusted for tumor stage and grade, cathepsin-D positivity was nearly twice as likely to be associated with node metastasis (p = 0.011). CONCLUSIONS: We demonstrated cathepsin-D expression in biopsies from a subset of patients with HNSCC and a strong association between this protease and cervical lymph node metastases. Cathepsin-D is a potential independent predictor of cervical lymph node metastasis in HNSCC and merits additional study.

Biomarkers, Tumor↗

Complications in skull base surgery for malignancy.

OBJECTIVES: To review a consecutive series of skull base surgeries, establish the rate of complications, and outline their prevention and management. STUDY DESIGN: A retrospective review of 107 consecutive intracranial/extracranial operations performed for malignancy that transgresses the skull base. METHODS: The hospital charts of 107 operations performed on 98 patients at the University of California at Davis Medical Center. The type of operation, cause of death, and complications were noted. RESULTS: The complication rate was 50.5%. Forty-eight patients had no complications. There were six perioperative deaths. The most common surgical complications were cerebrospinal fluid leak (11.2%), meningitis (4.8%), and wound breakdown (15%). The most common medical complications were pneumonia (6.5%), cardiac disturbance (4.7%), and electrolyte imbalance (3.7%). The only prior treatment that was accompanied by a significant increase in complications was previous surgery. CONCLUSIONS: patients who had cranial base surgery for the intracranial spread of head and neck cancer. The perioperative death rate is less than 4%. The major complications were at an acceptable rate.

Adult↗

Meyer procedure for severe laryngotracheal stenosis.

Many surgical procedures have been devised to manage laryngotracheal stenosis secondary to trauma. Laryngotracheal atresia is the most severe form and the most difficult to repair. The Meyer procedure is a three-stage operation that provides structural support that is covered with mucosa. A laryngotracheal trough is created and a carved trough-shaped cartilage graft is placed above and lateral to it in the first stage. The skin over the graft is replaced by buccal mucosa in the second stage. In the last stage, the cartilage graft with overlying mucosa is swung onto the trough as a composite flap replacing the anterior and lateral laryngeal and tracheal walls. Attempt at reconstruction was made in 8 patients. All but one lesion was secondary to endotracheal intubation. Two patients were unable to be taken to completion of the third stage. Of the remaining 6 patients, all have a functional voice and only 1 remains cannulated at night.

Adolescent↗

Heat shock protein and p53 expression in head and neck squamous cell carcinoma.

BACKGROUND: Heat shock proteins have been associated with the mutant form of the tumor suppressor gene, TP53, and with resistance to cancer chemotherapy. METHODS: Archival tissues from 50 patients with head and neck squamous cell carcinoma who received primary surgical resection were examined for p53, HSP27, and HSP70 by immunohistochemistry and correlated with tumor stage, grade, and 5-year survival (alive or deceased). RESULTS: Both heat shock proteins were strongly expressed in normal mucosa and in small (T1 and T2) tumors. Thirty (60%) of tumors were positive for p53, 43 (86%) for HSP27, and 34 (68%) for HSP70, with no association between p53 and heat shock protein expression. Twenty-five patients were alive (4 with disease), and 25 patients were deceased (9 from other causes). p53 Protein overexpression correlated with low-grade tumors. Only primary tumor site (i.e., oral cavity > larynx > oropharynx/base of tongue) and N stage were significantly associated with survival. CONCLUSIONS: Heat shock proteins are expressed in normal upper respiratory tract squamous mucosa, and their role in carcinoma remains unclear. None of the markers, p53, HSP27, or HSP70, demonstrated prognostic significance for 5-year survival. We confirm the recognized association of cervical lymph node metastases with decreased survival.

Biomarkers, Tumor↗

Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients.

BACKGROUND: Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. METHODS: The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. RESULTS: The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. CONCLUSIONS: Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.

Aged↗

Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base.

Neural cell adhesion molecules (N-CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular-trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N-CAM and Ki-67, a proliferation marker, with the avidin-biotin-peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N-CAM. Proliferation, measured by the presence of nuclear Ki-67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N-CAM is expressed in adenoid cystic carcinoma. The role of N-CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study.

Antibodies, Monoclonal↗

The effects of irradiation dose on the stiffness of cartilage grafts.

Various centers report irradiated cartilage graft absorption rates that differ quite widely. We postulated that a major factor governing this phenomenon might be irradiation dose. Irradiation produces collagen cross-binding and increased resistance to absorption of such material when implanted. Since cross-binding produces stiffening of collagen, cartilage grafts were exposed to increasing doses of irradiation and their elastic modulus was measured. The postulate was that increasing radiation doses will produce grafts of increasing stiffness. Sternal cartilage, harvested from horses, was cut into blocks of a standard size and irradiated to 4, 6, 8, and 10 megarads. The elastic modulus of each specimen and matched control were measured on an Instron flexural testing machine (Instron Corp, Canton, MA). Irradiation at all four doses reduced the elastic modulus of the cartilage grafts, with the lowest dose producing a reduction of 50% and the highest dose one of 90%. High-dose irradiation appears to lessen greatly the stiffness of cartilage grafts and may be responsible for increasing absorption of grafts in centers in which high doses are used.

Absorption↗

Prediction of major vascular injury in patients with gunshot wounds to the neck.

PURPOSE: To determine whether plain film and CT findings help predict the presence and severity of vascular trauma. METHODS: The records of 65 patients with gunshot wounds of the neck were reviewed. There were 58 men and 7 women ranging in age from 2 to 72 years. All had angiography of the cervical vessels; in addition, 64 had plain radiography, 22 had CT, and 14 had a barium swallow. The results of plain films, barium swallow, and CT scans were correlated. RESULTS: Eighteen patients (28%) had major vascular injury, which included 10 pseudoaneurysms, six vascular occlusions, four intimal injuries, and one arteriovenous fistula. Ten patients had prevertebral soft-tissue swelling (sensitivity, 59%; specificity, 77%), 14 had a bullet fragment close to a vessel (sensitivity, 78%; specificity, 36%), and 13 had missile fragmentation (sensitivity, 72%; specificity, 45%). CONCLUSION: Prevertebral soft-tissue swelling, missile fragmentation, and missiles adjacent to major vessels are useful but nonspecific radiographic signs and are present in many patients with normal angiographic findings. A knowledge of the physical findings, including the entry and exit wounds, plus the results of plain radiography and CT can help define bullet trajectories and guide angiographic evaluation.

Adolescent↗

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.

Adolescent↗

Internal carotid artery resection for invasion of malignant tumors.

BACKGROUND: To study the preoperative investigation and outcome of patients who underwent resection of the internal carotid artery for malignant disease. A retrospective analysis using a chart review of these patients was performed, and the results were analyzed. All patients were treated by one of us (U.K.N.) at the University of California-Davis Medical Center, Sacramento. A population of 18 patients who underwent a transcervical, transpetrosal, or petrocavernous resection of the internal carotid artery from 1976 to 1993 was studied. Preoperative study consisted of four-vessel arteriography, balloon test occlusion, electroencephalographic intraoperative monitoring, and, after 1990, single-photon emission computed tomographic scanning. Disease-free interval and neurologic complications were assessed. RESULTS: Two patients were alive and well without disease at 6 and 9 months postoperatively. One patient was alive and well at 12 months, and three have survived more than 2 years without recurrent tumor. Eleven patients died within 1 year of surgery (three postoperatively, six of recurrent disease, and two of unknown causes). One patient died of disease at 14 months. CONCLUSIONS: Internal carotid artery invasion by malignancy portends a poor prognosis. Carotid artery resection can provide reasonable palliation. Early results of skull-base surgery on patients with intrapetrous and petrocavernous carotid artery involvement are encouraging. Balloon test occlusion and single-photon emission computed tomographic scanning provide a valuable assessment of contralateral cerebral blood flow.

Adult↗

Neuralgia-like symptoms in a patient with an airgun pellet in the ethmoid sinus: a case report.

An unusual case of a retained airgun pellet in the ethmoid sinus is presented. The patient's only complaint was a severe neuralgic headache. Anatomical basis for this symptom, imaging and successful endoscopic removal of the foreign body are discussed. The philosophy for removal of innocuous foreign bodies, potential pitfalls in surgical management, and a review of the literature are included in the discussion.

Adult↗

Sphenoid sinus malignancies.

The sphenoid sinus has traditionally been considered a poorly accessible structure, situated deep in the center of the head and surrounded by vital structures. Aggressive benign and malignant tumors are usually considered to be inoperable because of the proximity of such structures, thus precluding the possibility of total extirpation. Using the transfacial-subcranial approach, lesions at this site can be totally excised. Significant tumor-free survival rates can be anticipated.

Carcinoma, Mucoepidermoid↗