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Biomedical subjects

S Rudy

Publications and source records attributed to S Rudy.

6 recordsLinked to original sources

Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer.

PURPOSE: To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m(2), and 17 patients received 120 mg/m(2). Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy. RESULTS: Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival. CONCLUSION: Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.

Adult↗

Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) comprises hypothalamic hamartoma, polydactyly, pituitary dysfunction, laryngotracheal cleft, imperforate anus, and other anomalies. Some patients with PHS have a bifid epiglottis, a rare malformation. Greig cephalopolysyndactyly syndrome (GCPS) comprises polydactyly with craniofacial malformations without the PHS malformations. Both disorders are caused by mutations in the GLI3 gene. Laryngoscopy on 26 subjects with PHS showed that 15 had a bifid or cleft epiglottis (58%) and none of 14 subjects with GCPS had a cleft epiglottis. The malformed epiglottis was asymptomatic in all of the prospectively evaluated subjects. One additional PHS subject was found to have bifid epiglottis and a posterior laryngeal cleft on autopsy. We conclude that bifid epiglottis is common in PHS but not GCPS. Posterior laryngeal clefts are an uncommon manifestation of PHS and are identified only in severely affected patients. The diagnosis of a bifid epiglottis should prompt a thorough search for other sometimes asymptomatic anomalies of PHS to provide better medical care and recurrence risk assessment for affected individuals and families.

Adolescent↗

Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer.

Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma (UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy.

Acute-Phase Reaction↗

Nursing care of the patient with trismus.

This paper discusses trismus (mandibular hypomobility), addressing its etiologies, relevant anatomy and pathophysiology, with the medical and nursing care of trismic patients commonly seen in the otolaryngology setting. It aims to raise awareness among ORL nurses about the sometimes subtle presentation of trismus and about the important role ORL specialists can play in detecting and treating this debilitating disorder.

Humans↗

Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche.

To determine the adrenal contribution to elevated plasma androgens in 31 young hyperandrogenemic women with acne and/or hirsutism, we compared their responses to ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (Cortrosyn) after administration of 1.5 mg dexamethasone the night before the test. Thirty and 60 min responses of plasma 17 alpha-hydroxypregnenolone (17-Preg), 17 alpha-hydroxyprogesterone, (17-prog), dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycortisol, and cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal androgen precursor. All patients had cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of steroid biosynthetic enzyme deficiencies, either mild congenital adrenal hyperplasia or the heterozygote state; after ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of 21-hydroxylase deficiency, 2 had elevated levels of 11-deoxycortisol compatible with 11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and DHEA, suggestive of 3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (DHEA and/or androstenedione) hyperresponsiveness to ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient 3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C lyase without impairment of cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have hyperplasia of the zona reticularis. Neither basal levels of plasma androgens (free testosterone and DHEA sulfate) nor menstrual history predicted which patients would have abnormal ACTH responses. Although 5 of 11 (45%) patients with acne alone had abnormal responses to ACTH, 10 of 14 patients with acne and hirsutism (71%) had abnormal responses to ACTH. We conclude that an adrenal contribution is found in about half of hyperandrogenemic women with acne and/or hirsutism. This adrenal androgen hyperresponsiveness is heterogeneous. Some patients may have mild forms of congenital adrenal hyperplasia. However, functional androgenic hyperresponsiveness to ACTH, which resembles an exaggeration of adrenarche, is the most common abnormality found. Such findings may provide an explanation for the clinical observation of exacerbations of acne with stress.

3-Hydroxysteroid Dehydrogenases↗