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Biomedical subjects

N Mirza

Publications and source records attributed to N Mirza.

At least 37 records · Page 2Linked to original sources

Paradoxical vocal fold motion: presentation and treatment options.

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.

Adolescent↗

Pilot study of organ preservation multimodality therapy for locally advanced resectable oropharyngeal carcinoma.

The purpose of this study was to determine the early efficacy and toxicity of a new multimodality organ-preservation regimen for locally advanced, resectable oropharyngeal squamous cell carcinoma (SCC). Patients with T3-4N0-3M0 or T2N2-3M0 oropharyngeal SCC were eligible for this Phase II study. Patients needed the physiologic reserve for surgery and technically resectable tumors. Induction carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) x 2 cycles (q21 days) were given. Objective responders received definitive radiotherapy (XRT), 70 Gy/7 weeks with concurrent weekly paclitaxel. Initially, the dose of paclitaxel was 50 mg/m2/week; because of mucosal toxicity it was reduced to 30 mg/m2/week. Patients with N2-3 disease received post-XRT neck dissection and 2 more cycles of "adjuvant" chemotherapy. In the first 22 patients, the neutropenic fever rate was 27%. Although there has been no grade IV-V toxicity from induction therapy, grade II-III toxicity resulted in an unacceptable delay in starting XRT in 14% of patients. The response rate to induction chemotherapy was 91%. Grade III mucositis occurred in all patients during concurrent chemoradiotherapy. One patient died of pneumonia during concurrent chemoradiotherapy after receiving 26 Gy and 3 doses of paclitaxel 50 mg/m2. No dose-limiting toxicity occurred in 15 patients treated with concurrent paclitaxel 30 mg/m2/week. Actuarial overall survival at 18 months is 82%; local-regional control is 86%. To date, distant metastases have not developed in any patients. This regimen has intense but acceptable acute toxicity. The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week. The treatment efficacy of this regimen (response rate and short-term local-regional and distant control) is encouraging. Accrual continues to obtain long-term toxicity, efficacy, and quality-of-life data.

Antineoplastic Combined Chemotherapy Protocols↗

Extensive intracranial xanthoma associated with type II hyperlipidemia.

Xanthomas are associated with a spectrum of medical conditions, most commonly disorders of lipid storage and lipid metabolism. They occur primarily in the subcutaneous tissues, especially along the Achilles tendon and the extensor tendons of the hands. Intracranial xanthomas are extremely rare. We present a case of an extensive xanthoma of the temporal bone in a patient with hyperlipidemia.

Adult↗

A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of paclitaxel given as a 96-hour continuous infusion during Weeks 1 and 5 of an accelerated radiotherapy schedule for the definitive treatment of advanced (nonmetastatic) unresectable squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Thirteen patients with Stage IV SCCHN were enrolled. Radiotherapy consisted of 70-72 Gy over 6 weeks, with a fractionation scheme of 2 Gy q.d. for 4 weeks followed by 1.6 Gy b.i.d. for 2 weeks, with no planned interruptions. Paclitaxel was administered over a 96-hour continuous infusion during Weeks 1 and 5 of radiotherapy at the following dose levels: Dose Level 1: 40 mg/m(2)/96-hours (3 patients); Dose Level 2: 80 mg/m(2)/96-hrs (5 patients); Dose Level 3: 120 mg/m(2)/96-hours (2 patients); and Dose Level 2A: 100 mg/m(2)/96-hours (3 patients). RESULTS: The MTD of Paclitaxel was 100 mg/m(2)/96-hours. All but one patient (who experienced progressive disease after receiving 61 Gy and both cycles of paclitaxel) completed therapy as planned. Dose-limiting toxicity occurred in both patients enrolled at Dose Level 3, with one patient experiencing Grade 4 diffuse moist desquamation and the other patient experiencing Grade 4 mucositis and febrile neutropenia. Thus, Dose Level 2A was opened and no dose limiting toxicity was noted. Grade 3 non-dose limiting mucositis and dermatitis occurred at all paclitaxel dose levels. There were no treatment-related deaths. All Grade 3 and 4 toxicities were reversible. Complete responses were seen in 8 of 13 patients, 4 patients achieved partial responses, and 1 patient had no response/progressive disease. CONCLUSIONS: Infusional paclitaxel over 96 hours during Weeks 1 and 5 of this accelerated radiotherapy schedule is feasible. The MTD of paclitaxel in this protocol was 100 mg/m(2)/96-hours. Dose-limiting toxicities were primarily enhanced epithelial reactions, but febrile neutropenia also occurred. All patients develop non-dose limiting Grade 3 skin and mucosal reactions, reflecting the high treatment intensity. This regimen merits further investigation.

Aged↗

Oral cavity and oropharyngeal tumors in human immunodeficiency virus-positive patients: acute response to radiation therapy.

BACKGROUND: The survival of patients with human immunodeficiency virus (HIV) has improved considerably with modern medical management. However, there remains surprisingly little information on treating head and neck neoplasms in HIV-positive patients. OBJECTIVE: To report our recent experience treating oral cavity and oropharyngeal tumors in HIV-positive patients. DESIGN AND PATIENTS: Retrospective analysis of a cohort of 8 HIV-positive patients with Kaposi sarcoma (KS), lymphoma, or squamous carcinoma of the oral cavity or oropharynx who were consecutively treated during a single year with radiation therapy at a tertiary care referral center. Length of follow-up was at least 2 years (mean, 2.5 years). RESULTS: All patients had partial and complete responses to treatment lasting until the last follow-up. However, we found that treatment was considerably better tolerated by patients with non-KS tumors, with fewer acute reactions and significantly less weight loss, despite larger treatment volumes and higher radiation doses, compared with patients with KS. Patients with non-KS tumors received a mean radiation dose of 62.6 Gy to 2636 cm3, yet lost only a mean of 0.1 kg in weight, whereas patients with KS were treated with a mean radiation dose of 19 Gy to a mean volume of 568 cm3, but lost a mean of 5.8 kg during treatment (P = .005) and on average sustained an additional grade of severity on a standard scale of mucosal reaction (P = .01). CONCLUSIONS: Oral cavity and oropharyngeal tumors in HIV-positive patients respond to radiation therapy, but there is a marked difference in the degree of acute reactions to treatment between patients with and without KS. Infection with HIV is not a contraindication when aggressive radiation therapy is needed in select patients.

Adult↗

The nasal airway and obstructed breathing during sleep.

Nasal obstruction whether partial or complete can influence the quality of sleep and has been strongly linked to the genesis of obstructed breathing during sleep (OBS). The relationship between nasal airflow and the process of upper airway collapse is complex. The first part of this article reviews the nasal anatomy with an emphasis on the sites of nasal obstruction, the effect of the nasal reflexes on the pulmonary system, and the pathophysiology of the development of OBS. The second part reviews the common causes of increased nasal resistance, the assessment of nasal passages, and the treatment options. This article also includes literature in support of and refuting the postulated mechanisms by which nasal obstruction can effect the respiratory system during sleep.

Humans↗

Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.

BACKGROUND: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation. PATIENTS AND METHODS: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. RESULTS: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%-100%) compared with 44% (95% CI: 1%-88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). CONCLUSIONS: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

Adult↗

Identification of p53 and human papilloma virus in Schneiderian papillomas.

Schneiderian papilloma of the nose is an unusual neoplasm with the propensity for local tissue destruction, recurrence, and malignant degeneration. Human papilloma virus (HPV) is related to a subset of sinonasal papillomas and has been implicated in the pathogenesis of cancer by interaction with the host p53 protein. Detection of p53 and HPV could be clinically useful as tumor markers for lesions with oncogenic potential. Thirty specimens for p53 were studied and nine (30%) stained positive. HPV was detected in six (20%). In the presence of p53, an odds ratio for carcinoma was 1.19:1, or 19% higher than expected. In the presence of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than expected. In the presence of HPV an odds ratio for finding an elevated amount of p53 was 2.2:1. The data support the hypothesis that HPV and p53 may interact in a novel manner and elevate the risk for neoplasia.

Biomarkers, Tumor↗

Sarcoidosis with nasal obstruction and septal perforation.

Although sarcoidosis is predominantly a pulmonary disorder, it often produces disease in the head and neck. For this reason, otolaryngologists should be comfortable in evaluating and treating the disease. The diagnosis of sarcoidosis often can be made with a biopsy of conjunctival or oral mucosa, even when disease manifestations are not apparent in those parts of the body. In a case of sarcoidosis involving the nose, a 54-year-old black man had a proliferation of small lumps on the tip of his nose. For many years, he had had daily epistaxis, anosmia and severe difficulty breathing through this nose. The bridge of his nose was deformed, and he had a large anterior septal perforation. Physical examination revealed palpable bilateral cervical lymphadenopathy. Laboratory test results were, for the most part, normal; however, fine-needle aspiration of one of the cervical lymph nodes showed multiple epithelioid granulomas with interspersed lymphocyte, and an incisional biopsy of the nasal tissue was highly suggestive of sarcoidosis. Unenhanced computed tomography also revealed widespread nasal inflammation and an abnormal soft tissue mass anterior to the maxilla consistent with chronic osteomyelitis. The patient's condition dramatically improved following treatment with oral prednisone; however, he considered undergoing reconstructive surgery for the noticeable nasal septal deformity.

Biopsy, Needle↗

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants.

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.

Adolescent↗

Metastatic follicular thyroid carcinoma to the paranasal sinuses: a case report and review.

Thyroid carcinoma metastatic to the paranasal sinuses is extremely rare, with only 11 cases reported in the English and European literature. We report a case of metastatic follicular thyroid carcinoma to the clivus with extension into the sphenoid and posterior ethmoid sinuses. Pathological diagnosis was obtained using an intranasal endoscopic biopsy. As with our patient, metastatic thyroid carcinoma may present with symptoms related to distant metastases rather than the primary lesion. Distant metastases in differentiated thyroid carcinoma portends a poor prognosis. Our case of metastatic thyroid carcinoma to the paranasal sinuses is summarized in the context of the 11 additional cases, and treatment options are discussed.

Aged↗

Mobilization kinetics of CD34+/Thy-1dim progenitor cells during recombinant human granulocyte-colony-stimulating factor administration in normal donors.

BACKGROUND: Allogeneic transplantation of granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) from normal related donors is effective in achieving engraftment with a relatively short period of posttransplantation aplasia. The optimal dose and composition of PBPC transplants are unknown. The CD34+/Thy-1dim progenitor cell subset is enriched for putative stem cells. STUDY DESIGN AND METHODS: The kinetics of the primitive subpopulation were prospectively studied in nine normal donors receiving recombinant human G-CSF (6 microg/kg) subcutaneously twice daily for 6 days for collection of PBPCs for allogeneic transplantation. RESULTS: The concentration (mean +/- SD) of the circulating CD34+/Thy-1dim subset increased from a baseline of 0.9 +/- 0.9 x 10(3) to 29.2 +/- 22.1 x 10(3) per mL on Day 4 and 38.0 +/- 29.8 x 10(3) per mL on Day 6. The level of CD34+/Thy-1dim cells was closely correlated with the overall level of CD34+ cells. At baseline, CD34+/Thy-1dim cells composed 21.1 percent of the total CD34+ cells, increasing to 36.3 percent at the peak of mobilization. CONCLUSION: CD34+/Thy-1dim cells are optimally mobilized on Days 4 to 6 of recombinant human G-CSF treatment.

Adolescent↗

Capnography during jet ventilation for laryngoscopy.

Jet ventilation is often used during laryngoscopy to permit improved visualization of the larynx and to eliminate a potentially flammable endotracheal tube when laser surgery of the airway is performed. Observation of chest wall movement and blood gas analysis are the usual standards for assessing the adequacy of ventilation during jet ventilation. It is reasonable to hypothesize that measurement of end-tidal CO2 concentrations during jet ventilation can be used to assess the adequacy of ventilation during jet ventilation. To test this hypothesis, end-tidal CO2 concentrations were determined during mechanical ventilation through an endotracheal tube and during jet ventilation. At the time that each end-tidal measurement was obtained, a sample of arterial blood was also obtained for later blood gas analysis. For both mechanical ventilation and jet ventilation, well defined relationships between end-tidal CO2 and arterial CO2 tensions were obtained. However, the relationships are distinct: the difference in arterial to end-tidal CO2 tension during supraglottic jet ventilation at a conventional respiratory rate was found to be 13.4 +/- 6.8 mm Hg (mean +/- SD) compared with 5.7 +/- 5.2 mm Hg obtained during conventional ventilation through an endotracheal tube.

Capnography↗

Influence of age on the 'nasal cycle'.

The nasal cycle is classicially defined as a side-to-side fluctuation in nasal engorgement and airflow, with period lengths ranging from approximately 1 to 5 hours. This cycle, as well as its variants (e.g., cyclic changes on one side of the nose only), is produced by alterations in autonomic tone of the nasal vasculature and reportedly correlates with a number of ultradian rhythms, including asymmetries in left:right cerebral electroencephalographic (EEG) activity and differential performance on visual/spatial psychological tasks. Since the pacemaker for the nasal cycle is believed to lie within the suprachiasmatic nucleus of the hypothalamus, and this nucleus evidences degeneration in later life, we sought to determine whether the nasal cycle or its variants changes with age. To achieve this end, we used a liquid crystal thermography exhalation monitor to measure relative airflow of the two nasal chambers at 15-minute intervals for 6 hours in 60 people representing four age categories: 18 to 29 years (n=12); 30 to 49 years (n=15); 50 to 69 years (n=13); and 70 to 85 years (n=20). Overall, the proportion of subjects exhibiting the alternating rhythmicity associated with the classic nasal cycle decreased with age. No association was present between nasal cycle parameters and scores on the Mini-Mental State Examination (MMSE). The results suggest that the classic nasal cycle may be a marker for age-related central nervous system changes.

Adolescent↗

Head and neck manifestations of plasma cell neoplasms.

Multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma are plasma cell neoplasms. They represent distinct manifestations of a disease continuum, whereby the clinical findings are critical to diagnosis. Plasma cell neoplasms are histologically similar, and distinguishing one from the other has significant implications for treatment and survival. Plasma cell neoplasms are relatively unusual malignancies of the head and neck region. We present a case series of plasma cell neoplasms involving the skull base, paranasal sinus, larynx, and mandible as an introduction to a complete review of the literature on plasma cell neoplasms of the head and neck area.

Adult↗

Allogeneic transplantation for recurrent or refractory non-Hodgkin's lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients.

We report the outcomes of 44 consecutive patients with non-Hodgkin's lymphoma (NHL) who participated in prospective studies of allogeneic transplantation after conditioning with thiotepa, busulfan and cyclophosphamide. Within a range of 27-57 years, the median age was 37. Of the 44 patients, 12 (27.2%) had high-grade lymphomas, 27 (61.4%) had intermediate-grade lymphomas, and five (11.3%) had low-grade lymphomas. Twenty-eight (63.6%) patients had chemotherapy refractory disease. Thirty (68.2%) patients had stage IV disease at the time of transplantation, involving the bone marrow in 19 (43.2%). Eight (18.1%) patients had undergone previous transplantation, and 13 (29.5%) patients had received high-dose CVP as induction within 2 months prior to transplantation. Thirty-eight (86.3%) patients had an HLA-identical donor, and 6 (13.6%) had a one-antigen mismatched related donor. Twenty (45.4%) patients received bone marrow and 24 (54.6%) received granulocyte colony-stimulating factor (G-CSF) mobilized stem cells. The graft-versus-host disease (GVHD) prophylaxis contained cyclosporine or tacrolimus in combination with either methylprednisolone in 32 (72.7%) patients or with methotrexate in 12 (27.2%) patients. The actuarial probability of disease-free survival at 2 years is 23% (95% CI 13%-40%). Donor stem cell use was associated with a significantly decreased risk of treatment-related toxicity (p < 0.001), but with an increased risk for GVHD and delayed fungal and viral infections. These infections are linked not only to the use of donor-stem cells, but also to the methylprednisolone in the GVHD prophylaxis regimen. Improvements in the outcome of patients with advanced NHL and undergoing allogeneic transplantation will depend on the development of effective and non-toxic regimens for conditioning, GVHD prophylaxis, and opportunistic infections prophylaxis.

Adult↗