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Biomedical subjects

S R Fisher

Publications and source records attributed to S R Fisher.

At least 19 recordsLinked to original sources

Second malignant neoplasms of the head and neck in survivors of retinoblastoma.

Retinoblastoma is a malignant tumor of the embryonic retina. Although it is rare, it is the most common primary eye tumor of childhood. Life expectancy following treatment is now excellent, but survivors who have heritable retinoblastoma face an increased risk of a second malignant head or neck neoplasm. A second neoplasm, which often occurs in the irradiated field of the original tumor, has become the most significant threat to the survival of these patients. We report the case of a young girl who was cured of her retinoblastoma only to later develop a second nonocular tumor that metastasized to the superficial parotid gland. She underwent a superficial parotidectomy and neck dissection, but the malignancy eventually recurred and required further surgery and radiation therapy. In this article, we discuss the etiology, incidence, sites of occurrence, and management options for a second malignant neoplasm in retinoblastoma survivors. The head and neck surgeon must be vigilant in the diagnosis and management of second neoplasms in this patient population because they often occur in irradiated fields; surgical management is important to patient survival.

Carcinoma↗

Molecular cloning, genetic mapping, and developmental expression of bovine POU5F1.

We describe isolation and characterization of the bovine ortholog of POU5F1 (bPOU5F1) encoding octamer-binding transcription factor-4 (Oct-4). The organization of bPOU5F1 is similar to its human and murine orthologs, and it shares 90.6% and 81.7% overall identity at the protein level, respectively. Transient transfection of luciferase reporter constructs in murine P19 embryonal carcinoma cells demonstrated that bPOU5F1 has a functional promoter and contains two enhancer elements, of which one is repressed by retinoic acid. bPOU5F1 was mapped to the major histocompatibility complex on chromosome 23. bPOU5F1 mRNA was detected by nested reverse transcription-polymerase chain reaction in immature oocytes and in in vitro-produced preattachment-stage embryos. Oct-4 in oocytes and in vitro-produced preattachment-stage embryos was demonstrated by indirect immunofluorescence. Confocal laser scanning microscopy revealed Oct-4 in both the inner cell mass and trophoblast cells of the blastocyst until Day 10 of development. Immunofluorescence performed on the outgrowths formed at Day 13 postfertilization from in vitro-produced Day 8 blastocysts showed Oct-4 staining in all cells. This expression pattern suggests that bPOU5F1 acts early in bovine embryonic development but that its expression is not restricted to pluripotent cells of the blastocyst.

Amino Acid Sequence↗

Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer.

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS: Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS: Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS: Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

Aged↗

Genetic mapping of five human chromosome 4 orthologues to bovine chromosomes 6 and 17.

Five loci that map to human chromosome 4 (HSA4) were selected to expand the bovine comparative linkage map. Loci included b-casein (CSN2), basic fibroblast growth factor (FGF2), immunoglobulin J chain (IGJ), interleukin 2 (IL2) and microsomal triglyceride transfer protein (MTTP). Polymorphisms for each locus were identified by either polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or single-strand conformational polymorphism (SSCP) analysis. The bovine genes for CSN2, IGJ and MTTP were mapped by linkage analysis to chromosome 6; FGF2 and IL2 mapped to chromosome 17. These data refine a position of chromosomal evolution to a small region between FGF2 and the previously mapped complement I factor (IF).

Animals↗

A phase I/II trial of twice daily irradiation and concurrent chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: This study was designed to test the toxicity and efficacy of a regimen of twice daily irradiation and concurrent multiagent chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: This was a prospective Phase I/II trial. Patients received 125 cGy b.i.d. to 7000 cGy with a 6 hr interfraction interval. Chemotherapy was given during weeks 1 and 6 of irradiation and consisted of a 5 day infusion of 5-fluorouracil at 600 mg/M2/day and 5 daily injections of cisplatin at 12 mg/M2/day. Two additional cycles of chemotherapy were given after the completion of radiotherapy. RESULTS: Forty-six patients were evaluable: 28 had technically unresectable disease and 18 had resectable tumors. All had Stage III or IV disease: 84% had T3 or T4 primaries while 53% had > or = N2 neck disease. The primary acute toxicity, confluent mucositis, was seen in 74% of patients. Late side effects occurred in four patients. Median follow-up is 36 months (range 25-44 months). Kaplan-Meier estimates of 2-year disease-free survival and overall survival are 65% and 73%, respectively, while 2-year local regional control and distant disease-free survival are 72% and 88%, respectively. Multivariate analysis revealed that resectability and receiving > 2 cycles of chemotherapy significantly influenced local regional control while age < 60 significantly influenced disease-free survival. CONCLUSION: This form of treatment can be delivered safely. The encouraging results have led to the initiation of a Phase III trial comparing this regimen with b.i.d. radiation alone.

Animals↗

Cytomegalovirus sialadenitis in patients with the acquired immunodeficiency syndrome: a potential diagnostic pitfall with fine-needle aspiration cytology.

We report three cases of cytomegalovirus (CMV) sialadenitis which presented as parotid gland nodules in patients infected with the human immunodeficiency virus. While CMV is known to widely infect patients with the acquired immunodeficiency syndrome (AIDS), we are aware of only a single report of CMV sialadenitis in a patient with AIDS (Pialoux et al.: Rev Infect Dis 1991;13:338). Utilizing fine-needle aspiration (FNA) cytology as the initial investigative modality, two cases were correctly diagnosed preoperatively while the third case displayed atypical features and was interpreted erroneously as carcinoma leading to surgical intervention. Upon review of these cases of CMV sialadenitis, the characteristic intranuclear inclusions are best identified with Papanicolaou (Pap) staining. CMV sialadenitis should be considered in the differential diagnosis of painless salivary gland enlargement in patients with AIDS. We believe this lesion can be diagnosed preoperatively with FNA and the interpretation is aided by evaluating both Pap- and Giemsa-stained material.

AIDS-Related Opportunistic Infections↗

Lentigo maligna melanoma of the head and neck.

Historically, lentigo maligna melanoma has been considered a "favorable" histological type of melanoma, and treatment by wide local excision was considered curative. A retrospective multivariate analysis of 143 head and neck patients with stage I lentigo maligna melanoma was performed from a database of 1067 head and neck patients followed at Duke Medical Center. Fifty-six percent of all lentigo maligna melanomas presented with lesions deeper than 0.76 mm, and 8% presented with stage II or III disease. Recurrent disease occurred in 45% of stage I patients, with a 5-year disease-free interval of 6 years and a median survival time of 10 years. Multivariate analysis demonstrated no significant difference in disease-free interval or survival by histological subtype. The data suggest that treatment should be based on tumor thickness and not histologic subtype.

Adult↗

Penile metastasis secondary to supraglottic squamous cell carcinoma: review of the literature.

We report an unusual supraglottic carcinoma metastasis to the penis. Review of the literature revealed more than 300 cases of metastatic lesions to the penis, excluding primary neoplasms from skin, urethra and blood. Of these metastatic neoplasms 16 originated above the diaphragm, only 4 of which were from the head and neck region. The most common neoplastic metastases to the penis in order of frequency were from the bladder, prostate, rectum and rectosigmoid areas, and kidney in 32, 30, 13 and 8% of the cases, respectively. The incidence of other primary tumor sites that metastasize to the penis is extremely rare.

Carcinoma, Squamous Cell↗

Therapeutic and prognostic considerations of head and neck melanoma.

Therapeutic considerations are discussed based on recurrence and survival statistics of 900 patients treated at Duke University Medical Center (Durham, NC). Approximately one-third of all patients developed recurrence. Factors affecting recurrence include tumor thickness, presence of positive regional nodes at diagnosis, and advanced Clark level. Patients with more than one adverse index had even higher rates of recurrence than with one alone. The 5-year survival of all patients after recurrence was 32%. Therapeutic decisions should include considerations that relate to patients' recurrence patterns and survival curves.

Academic Medical Centers↗

The effect of head and neck radiation therapy on voice quality.

Twenty-five patients with squamous cell carcinoma of the head and neck who received radiation therapy as their only form of treatment underwent a computer-assisted voice analysis before, and 6 months following treatment. Those with early laryngeal tumors had a significant improvement in intelligibility (P = .07), percent of sound voiced (P = .04), and sound perturbation. Those with nonlaryngeal tumors had no change in any measured parameters. Head and neck radiation therapy can significantly improve the voice quality of patients with laryngeal tumors, while having a minimal effect on the voice quality of those with nonlaryngeal tumors.

Carcinoma, Squamous Cell↗

Thin malignant melanomas of the head and neck.

Historically, Breslow classified thin melanomas as invasive lesions less than 0.76 mm in depth with rare instances of recurrence and mortality. From 1970 to 1990, 87 patients with thin head and neck melanoma were treated at Duke Medical Center. A computer-aided retrospective analysis was performed. Recurrence occurred in 30% of these patients; however, of the 66 patients seen at this institution prior to recurrence, only 8% recurred. Recurrence significantly shortened survival. Compared to an overall 84% 5-year survival, there was less than a 50% 5-year survival after recurrence. For thin melanomas, thickness did not affect survival. There was no difference in survival between thin melanomas and those ranging from 0.76 to 1.5 mm. A multivariate analysis was performed. The data suggest that thin melanomas of the head and neck may recur at a higher rate than previously reported and in addition, that they can be lethal.

Adult↗

Divergence of muscle and liver fructose 2,6-diphosphate in fasted exercising rats.

Previous studies demonstrate that nonexercising muscle may serve as a source of lactate for hepatic gluconeogenesis during long-term exercise. The concentration of fructose 2,6-diphosphate (F-2,6-P2), a signal molecule that accelerates glycolysis, was examined in liver and muscles of fed and fasted resting rats and in fasted rats run for 5, 15, or 30 min at 21 m/min (15% grade). Liver F-2,6-P2 decreased in response to fasting and exercise. White quadriceps (composed predominantly of type IIb fibers) F-2,6-P2 increased from 2.2 +/- 0.1 to 4.5 +/- 0.4 pmol/mg in the fasted rats in response to 30 min of treadmill running. No increase was observed in the red region of the quadriceps (composed of type IIa fibers). The fasted rats also exhibited a threefold increase in glucose 1,6-diphosphate (G-1,6-P2) in the white quadriceps after 30 min of exercise, whereas no significant changes were observed in the red quadriceps or in liver. The increases in F-2,6-P2 and G-1,6-P2 may be important in accelerating glycolysis and enhancing lactate production in muscles that are not glycogen depleted during long-term exercise.

Animals↗

Otolaryngologic management of patients with subdural empyema.

From 1979 to 1988, 17 patients presented to Duke University Medical Center for treatment of subdural empyema. Empyemas were caused by sinusitis in 53% of the patients and by otitis media in 12%. None of those with otologic causes required mastoid drainage, while all patients with sinus infections required sinus drainage. External frontoethmoidectomies were associated with a lower incidence of frontoethmoid re-exploration (P = 0.048), and antrostomies with a lower incidence of maxillary re-exploration (P = 0.111), than were more limited drainage procedures. Sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re-exploration (P = 0.167), neurosurgical reexploration (P = 0.048), and length of hospitalization (P = 0.020).

Adolescent↗