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Biomedical subjects

U K Sinha

Publications and source records attributed to U K Sinha.

At least 19 recordsLinked to original sources
PubMed2004

Relationships between stem cells and cancer stem cells.

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.

Animals↗
PubMed2002

Molecular pathology of head and neck cancer.

Squamous cell carcinoma of the head and neck region (HNSCC) is the sixth most frequent cancer worldwide, comprising almost 50% of all malignancies in some developing nations. In the United States, 30,000 new cases and 8,000 deaths are reported each year. Survival rates vary depending on tobacco and alcohol consumption, age, gender, ethnic background, and geographic area. This variability reflects the multifactorial pathogenesis of the disease. Early detection and diagnosis has increased survival but the overall 5 year rate of 50% is among the lowest of the major cancers. Differences between normal epithelium and cancer cells of the upper aerodigestive tract arise from specific alterations in genes controlling DNA repair, proliferation, immortalization, apoptosis, invasion, and angiogenesis. These proteins include both tumor suppressors and activating oncogenes which regulate a wide variety of intracellular signaling pathways. Included in these pathways are growth factor receptors, signal transducers, and transcription factors which regulate DNA damage response, cell cycle arrest, and programmed cell death. In head and neck cancer, alterations of three signaling pathways occur with sufficient frequency and produce such dramatic phenotypic changes as to be considered the critical transforming events of the disease. These changes include mutation of the p53 tumor suppressor, inactivation of the cyclin dependent kinase inhibitor p16, and overexpression of epidermal growth factor receptor (EGFR). This review will focus on the molecular changes which occur in these pathways and how they contribute to the pathogenesis of HNSCC.

Animals↗
PubMed2001

Reconstruction of pharyngeal defects using AlloDerm and sternocleidomastoid muscle flap.

OBJECTIVE: To report our experience in reconstructing pharyngeal defects that cannot be closed primarily, using acellular dermal matrix (AlloDerm, LifeCell Corp., Branchburg, NJ) and sternocleidomastoid (SCM) muscle flap. STUDY DESIGN: Prospective, nonrandomized, nonblinded study in the setting of an academic tertiary care medical center. METHODS: Fourteen patients underwent reconstruction of through-and-through defects of partial pharyngectomy for squamous cell carcinoma using AlloDerm graft. Primary closure of the defects was not possible because of substantial loss of pharyngeal tissue. The graft was reinforced with superiorly based SCM muscle flap in 10 patients. The remaining four patients did not receive any flap. Eleven lesions involved the lateral pharyngeal wall, and three were piriform sinus lesions. Patients were followed for a period ranging from 3 to 20 months. Outcome measures were determined on several parameters including graft take rate, evidence of graft contracture, postoperative complications, resumption of diet, intelligibility of speech, and decannulation. All patients were evaluated by a speech pathologist by means of a bedside swallowing examination. Five patients had videofluoroscopic studies. The three patients with piriform sinus lesions underwent videostroboscopic examination to assess vocal cord function. RESULTS: There was a high success rate for graft take. Two patients developed postoperative fistulas that resolved with conservative management. One of the 10 patients with SCM flap and one of the 4 patients without SCM flap developed fistulas. Clinically significant graft contracture or pharyngeal stenosis was not observed in any patients. All patients resumed oral intake. Ten patients resumed a normal diet, two tolerated a soft diet, and two could take purees. Decannulation was successful in all patients. Two of the three patients with piriform sinus lesions had vocal cord palsies after surgery resulting in breathy dysphonia. They underwent type I thyroplasty for vocal rehabilitation. All patients had intelligible speech. CONCLUSIONS: Thick AlloDerm, reinforced with SCM muscle or cervical soft tissue, provides a useful alternative option for reconstruction of pharyngeal defects that cannot be closed primarily. It is safe and effective and provides excellent functional outcomes.

Biocompatible Materials↗
PubMed1999

Surgery of the salivary glands.

Surgery of the salivary glands evolved rapidly after a greater understanding of the anatomy and pathologic processes affecting them was achieved. This article reviews the general and neurovascular anatomy of the major salivary glands. Understanding the anatomy of the salivary glands is a cornerstone of competent salivary gland surgery. The surgical techniques, potential pitfalls of surgery, and avoidance of postsurgical complications have been highlighted. Recent advances in surgical techniques are also presented.

Humans↗
PubMed1999

Endoscopic surgical management of sphenoid sinus disease.

OBJECTIVES: To assess the outcome of functional endoscopic sphenoid sinus surgery, and to determine the predictors of outcome. STUDY DESIGN: Retrospective chart review of 651 consecutive endoscopic sinus procedures performed between 1992 and 1997. SETTING: USC University Hospital, University of Southern California, Los Angeles. MATERIALS AND METHODS: Seventy-four patients (11.4% of all endoscopic procedures) with sphenoid sinus disease were selected. All 74 patients were mailed a sinusitis-specific questionnaire, and 46 of them (62.2%) responded. Outcome measures derived from clinician ratings were applied to all 74 patients, and those derived from self-report were applied to 46. Outcome measures were determined from patient questionnaires at a minimum of 6-month postoperative follow-up, operative complications, and clinician perceptual ratings. Patient questionnaires addressed general patient satisfaction, symptom score, and medication usage. A statistical analysis was performed using chi2 test, linear regression, and one-way nonparametric ANOVA. RESULTS: Favorable surgical outcomes based on general patient satisfaction (84.8%, n = 39) and clinician perceptual rating (78.4%, n = 58) were noted. Minor postoperative complications were noted in 10 patients (13.5%) and 8 patients (10.8%) needed revision endoscopic procedures during follow-up. Of the complications, eight (80%) occurred in revision endoscopic procedures. The use of an expanded, sinus-specific symptom score revealed far fewer favorable outcomes (56.5%, n = 26). Seven outcome predictors were established, although none of the predictors held for more than one of the six outcome measures used. CONCLUSION: Endoscopic sphenoid sinus surgery is safe and effective. An expanded symptom score is recommended to assess the outcome of this procedure.

Adult↗
PubMed1998

Managing the emergency airway in Le Fort fractures.

Le Fort fractures are a part of the facial fracture spectrum, sustained from significant forces of impact to the midface. The mechanism of airway obstruction in Le Fort fractures is attributed to midface instability with posterior inferior displacement into the oropharyngeal airway. Otolaryngologists often participate in the evaluation and management of such patients, securing the airway, if necessary. It is important, therefore, to understand the mechanisms responsible for acute airway obstruction in these types of fractures. A retrospective review of 64 cases of Le Fort fractures, representing a 3-year period, was performed to determine the factors responsible for acute airway obstruction. The review disclosed that airway obstruction is due most often to hemorrhage into the upper airway from multiple sources, with inability to handle blood and the oral secretions. An emergency airway was required by one third of the patients with Le Fort fractures in this review.

Adolescent↗
PubMed1996

Use of a mechanical microvascular anastomotic device in head and neck free tissue transfer.

BACKGROUND: The use of mechanical microvascular anastomotic systems for free tissue transfer has previously been reported. Currently, a commercially available coupling device (3M Healthcare, St. Paul, Minn) is widely used for various microvascular free flaps. However, to our knowledge, there are no reports in the literature describing the efficacy of this particular device in regard to free tissue transfer in head and neck reconstruction. OBJECTIVE: To describe the surgical technique, limitations, and guidelines for application of this system for vascular anastomosis in head and neck free tissue transfer. DESIGN: The microvascular anastomotic device was used in 79 head and neck free flaps: radial forearm (n = 28), rectus abdominis (n = 27), fibula (n = 12), lateral thigh (n = 4), iliac crest (n = 3), gracilis (n = 2), jejunum (n = 1), pectoral (n = 1), and lateral arm (n = 1). Follow-up ranged from 6 months to 2.5 years. SETTING: Two major teaching/referral medical centers. PARTICIPANTS: Seventy-six patients ranging in age from 19 to 86 years. INTERVENTION: A total of 105 anastomoses (17 arterial and 88 venous) were performed. OUTCOME MEASURES: Anastomotic times and patency rates were evaluated. RESULTS: the anastomotic times ranged from 8 to 18 minutes for the arteries (average, 10 minutes) and from 4 to 16 minutes for the veins (average, 5 minutes). None of the flaps resulted in venous congestion due to thrombosis at the anastomosis. Two arterial anastomoses resulted in thrombosis, one of which was detected intra-operatively and successfully salvaged with conventional suture anastomosis. CONCLUSIONS: The patency rates with the microvascular anastomotic system appear to compare favorably with those of standard suture techniques. The major advantage is that the time of venous anastomosis is reduced, thereby decreasing the total ischemic time. An additional advantage is the ease with which anastomoses can be performed when the vessels are deep within a wound, where suture placement is difficult.

Adult↗
PubMed1996

Temporal bone findings in Alzheimer's disease.

Sensorineural hearing loss has been reported in Alzheimer's disease (AD) and a topographically specific pattern of degeneration in the central auditory system has been described. Although peripheral visual and olfactory systems have been extensively studied, there is no report of peripheral auditory system abnormalities in AD patients. Comparison of temporal bones from eight AD patients with those from eight non-AD controls revealed a significant difference in the percentage of remaining hair cells, peripheral processes, and spiral ganglion cells in the basal cochlear turn but no significant differences in the overall percentage between the two groups. Furthermore, special stains (thioflavin S and Bielschowsky's silver impregnation) of temporal bone nervous tissue from AD patients did not show neuritic plaques and neurofibrillary tangles. It is unclear whether the differences between the two groups in the basal portion of the cochlea are due to AD or some other process, such as presbycusis. However, lack of significant degeneration in other parts of the cochlea and absence of neurofibrillary tangles and neuritic plaques in all eight patients may suggest that the peripheral auditory system, unlike the peripheral visual and olfactory systems, is not involved in AD. A larger sample of AD patients is necessary to clarify the peripheral auditory system findings in the present study.

Aged↗
PubMed1995

Safety of thyroidectomy in residency: a review of 186 consecutive cases.

A retrospective review was performed to assess the surgical complications of thyroidectomy performed by otolaryngology residents under close supervision by faculty. One hundred eighty-six consecutive cases of thyroidectomy performed by the residents in the Department of Otolaryngology--Head and Neck Surgery at the University of Southern California were reviewed. Sixty-nine percent of thyroidectomies were performed for malignant or possible malignant diseases, and 31% were performed for benign conditions. Transient (less than 2 weeks in duration) hypocalcemia occurred in 26% of the patients; the vast majority of cases resolved within the first week. Five percent of the patients developed persistent hypocalcemia requiring prolonged replacement therapy. The incidence of unexpected postoperative permanent vocal cord paralysis was 0.9%. These complication rates are comparable to those in previously published large series on results of thyroidectomy. Thyroidectomy performed in an otolaryngology residency training program is a safe procedure when closely supervised by experienced faculty.

Adolescent↗
PubMed1995

Sensory recovery in noninnervated free flaps for head and neck reconstruction.

Recent studies have reported sensory recovery in innervated ("sensate") microvascular free flaps used for oromandibular reconstruction. To evaluate the efficacy of sensate free flaps used for head and neck reconstruction, the natural outcome of noninnervated flaps must be known. Data on the natural recovery of sensation in noninnervated head and neck free flaps are lacking in the literature. This study evaluates the degree of spontaneous sensory reinnervation in noninnervated microvascular free flaps used for reconstruction of a variety of head and neck defects. Eighteen flaps were evaluated--9 fibula osseocutaneous and 9 radial forearm. The fibula flaps were used to reconstruct composite defects of the mandible and oral cavity mucosa. The radial forearm flaps were used to reconstruct defects resulting from floor of mouth resection (3), total glossectomy (2), pharyngectomy (1), full-thickness cheek (1), and facial skin (2). Sensation to pinprick, light touch, and temperature discrimination were tested over the skin paddle at time intervals ranging from 6 to 24 months. The pattern of sensory reinnervation in these noninnervated flaps over time and by location is discussed.

Bone Transplantation↗
PubMed1993

Abnormal neuritic architecture identified by Di-I in Pick's disease.

The fluorescent stain Di-I combined with confocal microscopy identified an abnormal neuritic pattern in the cortices of frontal and anterior temporal lobes in postmortem tissues from patients with Pick's disease (PD). Focal, dense neuritic aggregates 50 to 200 microns in diameter were scattered throughout all cortical layers. The three-dimensional analysis provided by confocal microscopy revealed the neuritic clusters to consist of enlarged, randomly arrayed, dystrophic neurites that were not associated with amyloid deposits, astrocytic processes or capillaries. In the intervening neuropil, there were fewer neurites compared to controls. The occipital cortex, which is unaffected in PD, showed a neuritic architecture comparable to normal controls as did affected brain tissues from patients with Alzheimer's disease or remote, ischemic infarction. This neuritic pattern is, thus far, unique to PD and may reflect the loss of specific subpopulations of cortical neurons and proliferation of neurites of the remaining neurons.

Aged↗
PubMed1993

Auditory system degeneration in Alzheimer's disease.

We observed a highly topographically specific and consistent pattern of degeneration in the auditory system of Alzheimer's disease (AD) patients. Senile plaques (SP) and neurofibrillary tangles (NFT) were distributed throughout the ventral nucleus of the medial geniculate body (MGB) and the central nucleus of the inferior colliculus (IC) in nine of nine AD patients. Adjacent nuclei within the MGB and IC were consistently spared. NFT and SP were also present in the primary auditory and the auditory association cortices. In all control tissues, there were neither SP nor NFT in any of the above sites. The cochlear nuclei were normal in tissues from both AD and control patients. The ventral nucleus of the MGB is the major thalamic relay station for auditory function and receives fibers from neurons of the central nucleus of the IC, with projections arranged tonotopically in a laminar pattern corresponding to a gradient of high-to-low frequency ranges. The degenerative changes distributed throughout these nuclei suggest that neuronal loss may include all frequency ranges in AD. In contrast, the clinical features of presbycusis in elderly patients include only high-frequency loss due to lesions peripherally in the cochlea or auditory nerves, rather than in the central auditory nuclei. These histologic changes in the brains of AD patients may provide an additional basis for altered cognitive function due to primary sensory deafferentation.

Aged↗
PubMed1987

Computer-aided three-dimensional reconstruction of the cochlear nerve root.

Computer-aided three-dimensional reconstruction techniques have been used for reconstruction of the cochlear nuclei and the cochlear nerve root. The cochlear nuclei, the nerve root, and the other adjacent structures were studied in serial frontal and horizontal sections. Boundaries of these structures were digitized into a computer and eight three-dimensional models were produced. Two solid models (reconstructions) showed the spatial surface topography, while the others revealed the appearance of the nerve root within the nuclei. The reconstructions also showed the position of the tenia of the tela choroidea on the surface of the nuclei and its relation to the root. This knowledge makes it possible to use the tenia as a landmark for determination of the root position within the nuclei. As the nerve enters the nucleus and forms the root, there is an appreciable reduction in its thickness. At the same time, the distance between the nuclei surface and the root, which has a cone shape, increases. The cone is curved along its longitudinal axis toward the inferior cerebellar peduncle. The top of the root borders the dorsal cochlear nucleus. This study stems from work in this institution on placement of the central electroauditory prosthesis on the cochlear nuclei surface. The results obtained further knowledge of the anatomy of the nuclei, specifically the areas used for the prosthesis implantation and the underlying tissue.

Brain Stem↗
PubMed1987

Anatomical relationships of the cochlear nuclei and the pontobulbar body: possible significance for neuroprosthesis placement.

The pontobulbar body (PBB) is located in the cerebellopontine angle caudally to the cochlear nuclear complex (CN). We found the common boundary between these two structures on the surface of the brain stem as well as within it. We used the Kluver-Barrera staining technique to characterize different neuronal types adjacent to the boundary. Although the majority of them in the CN were globular, we also saw a substantial number of spherical neurons. Neurons in the PBB were substantially different in shape and were mainly angular. The boundary between the PBB and CN at their closest contact runs around the caudal side of the ventral cochlear nucleus and the most proximal part of the eighth nerve. In the more dorsal region, the PBB is completely separated from the CN by the brain stem tissue. In the ventral region, the PBB runs between the seventh and eighth nerves, and it is adjacent to both. These results might aid accurate placement of the central electroauditory prosthesis and further understanding of the general anatomy of the cerebellopontine angle.

Adult↗
PubMed1987

Three-dimensional computer-aided reconstruction of the pontobulbar body.

The pontobulbar body (PBB) has a crescent-like shape and runs along the caudal border of the cochlear nuclei (CN) on the lateral surface of the brain stem and then extends rostrally to the root of the trigeminal nerve. Three-dimensional computerized reconstruction methods have been used to produce two models that show the surface topography of the PBB and CN together, while other models revealed the appearance of different sides of the PBB only. The models accurately localized the common boundaries between the PBB and CN. Inside the brain stem, the boundary between the ventral CN and PBB was not always clear in sections stained for cell bodies and myelinated fibers. Close relationships between the PBB and pontine nuclei in the ventral portions of the pons were demonstrated. The reconstructions also showed the position of the tenia of the inferior velum of the fourth ventricle in relation to the PBB and CN. In contrast to the CN, only a relatively small portion of the PBB was located within the fourth ventricle. Results may be useful to work underway in this institution on implantation of the central electro-auditory prosthesis. Results might also be useful for further development of the surgical anatomy of the cerebellopontine angle.

Computer Simulation↗
PubMedDate not supplied

Frontotemporal reconstruction with hydroxyapatite cement and the radial forearm free flap.

BACKGROUND: Contemporary surgical reconstruction of extensive frontal and temporal bony and soft tissue defects requires the use of myocutaneous free flaps. These flaps are associated with donor site morbidity, lengthy operative time, and lack of rigid protection for the brain. To circumvent these problems, we introduce a new surgical technique for reconstruction of frontotemporal defects. OBJECTIVES: To evaluate and discuss hydroxyapatite and radial forearm free flap (RFFF) reconstructive options for patients with soft tissue and bony defects in the frontal and temporal regions after ablative cancer surgery. METHODS: Eight consecutive patients with extensive soft tissue and bony defects in the frontal and temporal regions underwent primary reconstruction with hydroxyapatite cement for replacement of bone, and the RFFF for soft tissue coverage. Patient follow-up ranged from 6 to 48 months. Outcome was determined in terms of immediate and delayed postoperative complications, donor site morbidity, and long-term aesthetic results. RESULTS: Excellent bony and soft tissue contour restoration was achieved in all patients. The bony and soft tissue volume was maintained throughout the follow-up period. One patient had a stroke. No other postoperative complications were encountered. Morbidity from RFFF harvest was minimum. CONCLUSIONS: The combination of hydroxyapatite cement and the RFFF is a viable alternative to the conventional myocutaneous free flap reconstruction of extensive frontotemporal defects. This technique provides excellent aesthetic results, provides rigid protection for the brain, produces minimal and well-tolerated donor site morbidity, and reduces operative time by avoiding intraoperative changes in patient position.

Aged↗