Biomedical subjects

R V Smith

Publications and source records attributed to R V Smith.

At least 19 recordsLinked to original sources

PubMed2006

Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray.

Our group has initiated experiments to epigenetically profile CpG island hypermethylation in genomic DNA from tissue specimens of head and neck squamous cell carcinoma (HNSCC) using a microarray of 12,288 CpG island clones. Our technique, known as a methylation-specific restriction enzyme (MSRE) analysis, is a variation of the differential methylation hybridization (DMH) technique, in that it is not an array comparison of two DNA samples using methylation-specific restriction enzymes. Instead, it is a comparison of a single DNA sample's response to a methylation-sensitive restriction enzyme (HpaII) and its corresponding methylation-insensitive isoschizomer (MspI). Estimation of the reproducibility of this microarray assay by intraclass correlation (ICC) demonstrated that in four replicate experiments for three tumor specimens, the ICC observed for a given tumor specimen ranged from 0.68 to 0.85 without filtering of data. Repeated assays achieved 87% concordance or greater for all tumors after filtering of array data by fluorescence intensity. We utilized hierarchical clustering on a population of 37 HNSCC samples to cluster tumor samples with similar DNA methylation profiles. Supervised learning techniques are now being utilized to allow us to identify associations between specific epigenetic signatures and clinical parameters. Such techniques will allow us to identify select groups of CpG island loci that could be used as epigenetic markers for both diagnosis and prognosis in HNSCC.

Blotting, Southern↗

PubMed2001

Assessing the effectiveness of regulatory controls on farm pollution using chemical and biological indices of water quality and pollution statistics.

Water quality was measured in 42 streams in the Colebrooke and Upper Bann catchments in Northern Ireland over the period 1990-1998. Despite ongoing pollution control measures, biological water quality, as determined by the invertebrate average score per taxon (ASPT) index, did not improve and there was no appreciable decline in recorded farm pollution incidents. However, the lack of decline in pollution incidents could reflect changes in detection policy, as a greater proportion of incidents were recorded from less polluting discharges such as farm-yard runoff. In contrast, there was an improvement during 1997 and 1998 in annual chemical water quality classification based on exceedence values (90th percentiles) for dissolved oxygen, ammonium and BOD concentrations. In 1998, 11.9% of streams were severely polluted compared to 26.2% in 1990, while the proportion classed as of salmonid water quality, increased from 40.5% in 1990 to 59.6% in 1998. Although water quality in 1996 did not improve relative to 1990 values, there was a notable increasing trend from 1990 in the numbers of samples taken during the summer which had good water quality with low ammonium (<0.6mgN l(-1)) and high dissolved oxygen (> 70% sat). The trend for samples with low BOD (<4 mgl(-1)) was more erratic, but an improvement was apparent from 1994. These improvements in chemical water quality suggest that point-source farm pollution declined after 1990. The fact that this was not reflected in stream biology may reflect the limited time scale for biological recovery. An important factor preventing biological recovery may be the high pollution capacity of manures and silage effluent, so that even reduced numbers of farm pollution incidents can severely perturb stream ecosystems. The intractable nature of farm pollution suggests that there is a need to consider an interactive approach to problem resolution involving both farmers and regulators.

Agriculture↗

PubMed2001

Changes in soil organic carbon storage under grassland as evidenced by changes in sulphur input-output budgets.

Information about temporal changes in soil organic carbon (C) pools may be obtained indirectly from changes in input-output budgets of organically combined nutrients such as sulphur (S). Sulphur budgets were therefore evaluated for Northern Ireland (NI) for the period 1940-1990, inclusive. These budgets indicated that the land or soil had acted first as a sink but then as a source for S, and that reserves of soil S built up between 1940 and 1965 were totally depleted by the mid-1980s. Pooled data from six long-term soil-monitoring sites on undisturbed grassland suggested that negative S budgets from the late-1970s onwards had been due to the net mineralization of soil organic matter and thus were indicative of net losses of organic C from surface soil horizons. There was some evidence that the decline in rainfall and fertiliser S inputs from the mid-1960s may have precipitated the breakdown of soil organic matter.

Animal Feed↗

PubMed2001

Stage 4 squamous cell carcinoma of the tongue in a child: complete response to chemoradiotherapy.

This report describes a complete response to a chemoradiotherapy regimen in a child with an advanced and unresectable squamous cell carcinoma of the tongue. An 8-year-old girl had stage 4 squamous cell carcinoma of the tongue (T4N2M0), causing severe trismus and dysphagia. She received hyperfractionated external beam radiotherapy (total 74.4 Gy) and concomitant intravenous infusion of hydroxyurea (0.313 mg/m2 per min) for 43 days. Grade 3 mucositis and myelosuppression were the main toxicities. There was marked symptomatic improvement, and the patient achieved a complete response. She is disease-free 24 months after treatment, and all the acute symptoms have resolved. The regimen was well tolerated with acceptable toxicity and led to a complete objective response. This regimen needs further evaluation to confirm its efficacy and to ascertain its long-term effects in children.

Adult↗

PubMed2000

A spatial study of denitrification potential of sediments in Belfast and Strangford Loughs and its significance.

The C2H2 inhibition technique was employed to study seasonal denitrification potential rates in sediment slurries from tidal and subtidal sites in Belfast and Strangford Loughs, Northern Ireland. A comparison of denitrification rates obtained from this method with those obtained from the 15N-gas flux method generally showed good agreement. Depth profiles measured up to 1 m showed that denitrification decreased with depth, with highest values in the 0-5-cm fraction. For the Belfast Lough tidal system a multiple regression model was developed which explained 83% of the variation in denitrification potential. The independent variables were water content, sediment temperature, total oxidizable N in porewater and total organic N. The highest rate of denitrification potential, 2100 micromol N m(-2) h(-1), was found in areas where there was a high anthropogenic input of nutrients. Denitrification in sediments in both loughs can play a potentially significant role in removal of NO3- from the overlying water. In Belfast Lough the overall denitrification potential rate matched the external NO3-N inputs, whilst in Strangford Lough it exceeded it by sixfold, which suggests a potential to remove future additional anthropogenic inputs to the Lough.

Acetylene↗

PubMed2000

Long-term swallowing problems after organ preservation therapy with concomitant radiation therapy and intravenous hydroxyurea: initial results.

OBJECTIVE: To evaluate the long-term effects on swallowing function of concomitant continuous infusion hydroxyurea and hyperfractionated radiation therapy used to treat advanced head and neck carcinoma. DESIGN: A prospective evaluation of swallowing function was performed on an inception cohort by analyzing posttreatment videoflouroscopic swallow function studies using radiological descriptors for pharyngeal transport abnormalities and temporal measures of structural movements, as well as by conducting patient interviews to assess alimentation, more than 1 year after tumor treatment (range, 52-124 weeks; median, 70 weeks). SETTING: Academic tertiary care referral medical center. PATIENTS: Ten patients, aged 44 to 71 years, with stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx. MAIN OUTCOME MEASURE: Radiographic and temporal swallow abnormalities, as well as functional status, were documented and compared with published norms and results of earlier swallowing studies when possible. RESULTS: Pharyngeal transport dysfunction and anterior segment abnormalities, manifested by epiglottic dysmotility, vallecular residue, laryngeal penetration, or aspiration, were evident in all 10 patients. Posterior segment abnormalities, such as pharyngeal stasis, constrictor dysmotility and piriform residue were documented in 8 patients. Three patients developed late aspiration, and the majority of patients showed persistent or worsened delay in laryngeal movement compared with their earlier posttreatment evaluations. Also, 3 patients developed a hypopharyngeal stricture, and 6 patients continued to require gastrostomy tube supplementation beyond 1 year. There was no association between site of primary, duration to swallowing evaluation, and severity of dysfunction. CONCLUSION: Prolonged and debilitating functional swallowing abnormalities may occur after this aggressive concomitant chemotherapy and radiotherapy regimen.

Adult↗

PubMed2000

The workforce in otolaryngology-head and neck surgery: moving into the next millennium.

OBJECTIVE: The goal was to examine the current scope of otolaryngologists' practices, their geographic distribution, and the roles otolaryngologists and other specialists play in caring for patients with otolaryngic and related conditions of the head and neck. STUDY DESIGN: A large national survey and administrative claims databases were examined to develop practice profiles and compile a physician supply for otolaryngology. A focus group of otolaryngologists provided information to model future scenarios. RESULTS: The current and predicted workforce supply and demographics are at a satisfactory level and are decreasing as a proportion of the increasing population. Empiric data analysis supports the diverse nature of an otolaryngologist's practice and the unique role for otolaryngologists that is not shared by many other providers. Together with the focus group results, the study points to areas for which more background and training are warranted. CONCLUSIONS: This study represents a first step in a process to form coherent workforce recommendations for the field of otolaryngology.

Adult↗

PubMed2000

Early wound complications in advanced head and neck cancer treated with surgery and Ir 192 brachytherapy.

OBJECTIVES: Brachytherapy, either as primary or adjuvant therapy, is increasingly used to treat head and neck cancer. Reports of complications from the use of brachytherapy as adjuvant therapy to surgical excision have been limited and primarily follow Iodine 125 (I125) therapy. Early complications include wound breakdown, infection, flap failure, and sepsis, and late complications may include osteoradionecrosis, bone marrow suppression, or carotid injuries. The authors sought to identify the early wound complications that follow adjuvant interstitial brachytherapy with iridium 192 (IrS92). STUDY DESIGN: A retrospective chart review of all patients receiving adjuvant brachytherapy at a tertiary medical center over a 4-year period. METHODS: Nine patients receiving Ir192 brachytherapy via afterloading catheters placed during surgical resection for close or microscopically positive margin control were evaluated. It was used during primary therapy in six patients and at salvage surgery in three. Early complications were defined as those occurring within 6 weeks of surgical therapy. RESULTS: The overall complication rate was 55% (5/9), and included significant wound breakdown in two patients, minor wound dehiscence in three, and wound infection, bacteremia, and local tissue erosion in one patient each. All complications occurred in patients receiving flap reconstruction and one patient required further surgery to manage the complication. Complication rates were not associated with patient age, site, prior radiotherapy, timing of therapy, number of catheters, or dosimetry. CONCLUSIONS: The relatively high complication rate is acceptable, given the minor nature of most and the potential benefit of radiotherapy. Further study should be undertaken to identify those patients who will achieve maximum therapeutic benefit without prohibitive local complications.

Aged↗

PubMed2000

Workforce issues for the academic otolaryngologist.

BACKGROUND: The current medico-economic environment has led to profound changes in our health care system and questions of physician surplus. These issues have particularly affected the academic health care system, as research funding and departmental support have decreased, and many young otolaryngologists are questioning academic careers because of these uncertainties. The current study was undertaken to assess the workforce environment for the academic otolaryngologist, particularly the young physician. METHODS: Surveys were sent to the academic chairmen of all accredited otolaryngology residency programs in the United States, requesting information on faculty appointments--actual and projected-as well as subspecialty appointments and expectations of young faculty. RESULTS: The response rate was 60% (59/98). Faculty additions have been relatively stable from 1994 to 1998, with approximately 37 assistant professor and 5 associate professor positions filled yearly. Faculty additions were the result of departmental expansion in 83% of cases and spanned many subspecialties. The subspecialty positions most frequently added from 1994 to 1998 were generalists (57), head and neck oncologists (53), pediatric otolaryngologists (48), and otologists (39), with generalists filling 15 positions in 1998. Ninety-three percent of programs anticipate faculty additions in the next 5 years; most will be at the assistant professor level (77%), with 30% of positions for generalists, 20% for head and neck oncologists, and 18% for pediatric otolaryngologists. Faculty expectations are primarily clinical, with research being least important. CONCLUSIONS: Academic positions are available for the young otolaryngologist, particularly in the fields of general otolaryngology, head and neck oncology, and pediatric otolaryngology.

Data Collection↗

PubMed2000

Reversible sensorineural hearing loss following administration of muromonab-CD3 (OKT3) for cadaveric renal transplant immunosuppression.

This prospective study is a follow-up to a case report noting reversible sensorineural hearing loss after administration of OKT3 for immunosuppression in a steroid-resistant renal cadaveric transplant patient who was rejecting his transplant. The objective is to determine the interval estimate for incidence of sensorineural hearing loss following treatment with OKT3. Seven patients were admitted to the Renal Transplant Service at Montefiore Medical Center from July 1996 to July 1997 with steroid-resistant rejection of renal cadaveric transplants and received OKT3 as an immunosuppressant. All 7 patients received 3 audiograms: the first, prior to the administration of the first dose of OKT3, the second, 48 to 72 hours after administration of OKT3, and the third, approximately 2 weeks after administration of OKT3. Five of the 7 patients (71%) demonstrated a sensorineural hearing loss of 15 dB or greater at frequencies of 8 to 12 kHz. Four of the 5 patients with audiographic changes had near-complete to complete recovery of their high-frequency thresholds after discontinuation of the drug regimen. In conclusion, OKT3 can cause sensorineural hearing loss. This side effect is mainly reversible after 2 weeks following discontinuation of the drug. Patients receiving OKT3 should be forewarned of this possible side effect prior to the administration of OKT3.

Audiometry, Pure-Tone↗

PubMed2000

Team approach for closure of oroantral and oronasal fistulae.

Oroantral and oronasal fistulas present with a broad range of causation, size, duration, and extent of infection involving the nose and paranasal sinuses. Accurate diagnosis of the extent of the disease with appropriate radiographic evaluation will guide the surgeon to select an approach that addresses all of the infected sites. When significant sinus disease is found, an endoscopic approach to restoring drainage in all of the involved sinuses can promote predictably successful closure of oroantral and oronasal fistulas. The multispecialty team approach to this disease, with the concomitant management of the sinusitis and fistula closure, is a significant advance in the successful management of this chronic condition.

Adult↗

PubMed1999

Benign parotid hypertrophy on +HIV patients: limited late failures after external radiation.

PURPOSE: Although 8-10 Gy of external radiation therapy for +HIV associated parotid hypertrophy has achieved high response rates, the responses were transient with only 1/12 of patients retaining cosmetic control at median follow-up procedures of 9.5 months. Retreatment for failures after 8-10 Gy has also been unsatisfactory. Having shown that 24 Gy of external radiation therapy for benign parotid hypertrophy produced more durable cosmetic control than 8-10 Gy, we now report on longer follow-up periods on a group of patients receiving 24 Gy. MATERIALS AND METHODS: Twenty +HIV patients with clinical and radiographic evidence of lymphoepithelial lesions of the parotid were treated with 24 Gy of external radiation therapy using daily 1.5 Gy fractions; parallel opposed technique and 6 MV photons were used in 19 patients, and unilateral electron treatment was performed for one patient. RESULTS: With a mean follow-up period of 24 months, the cosmetic control appears durable. We have had no late failures past 24 months. Two patients have complained of modest xerostomia. There was no correlation with size of the cyst and eventual cosmetic result. CONCLUSIONS: Twenty-four Gy produces durable parotid control for HIV associated lymphoepithelial lesions of the parotid glands in +HIV patients. Failures after 2 years are uncommon and the side effects have been tolerable.

Female↗

PubMed1999

Pharyngeal transport dysfunction consequent to an organ-sparing protocol.

OBJECTIVE: To investigate the effects of a protocol of concomitant intravenous hydroxyurea and hyperfractionated, accelerated, external-beam radiation therapy on the swallowing mechanism of patients with advanced-stage head and neck cancer. DESIGN: Posttreatment videofluoroscopic swallow function studies, using images of single-bolus swallows of low-density liquid barium, were analyzed in real time, slow motion, and frame by frame using an integrated system that allows objective analysis of video recordings through image processing and digitization (Kay Elemetrics Computerized Swallowing Station). Radiological descriptors were used for pharyngeal transport abnormalities, and temporal measures were obtained of structural movements. SETTING: Academic, tertiary care, referral medical center. PATIENTS: Fifteen consecutive patients with previously untreated, stages III and IV, nonmetastatic squamous cell carcinoma of the head and neck who underwent a phase 1 study of prolonged infusion hydroxyurea therapy in combination with hyperfractionated, accelerated external-beam radiation therapy for their disease. RESULTS: All patients had anterior pharyngeal segment dysfunction, characterized by no epiglottic movement and slowed laryngeal motility (1.011 +/- 0.379 seconds [mean +/- SD). Anterior pharyngeal dysfunction was more severe in patients with primary tumors of the hypopharynx than in those with cancer of the oropharynx. Twelve (80%) of our patients demonstrated posterior pharyngeal segment dysfunction characterized by impaired pharyngeal constrictor motility. All 15 patients displayed pharyngeal stage abnormalities that limited bolus transport and clearance. CONCLUSIONS: Severe pharyngeal physiological abnormalities were present that led to impaired bolus transport and that were frequent and debilitating consequences of this organ-sparing protocol. Long-term follow-up of this group will be required to assess the permanence of the abnormalities.

Adult↗

PubMed1999

Comparison of postoperative cardiopulmonary examinations and chest radiographs to detect pulmonary complications after adult tracheotomy.

OBJECTIVE: To prospectively evaluate the effectiveness of clinical cardiopulmonary examination compared with that of chest radiography in detecting postoperative pulmonary complications after tracheotomy in adults. METHODS: One hundred consecutive patients undergoing tracheotomy were evaluated. Pulmonary complications were recorded, and the effectiveness of the physical examination was compared with that of the chest x-ray in detecting these complications. Patient age, sex, diagnosis, urgency of the procedure, and anesthetic technique were evaluated to determine any relationship to postoperative complications. RESULTS: Of the 100 patients, 87 patients underwent postoperative chest radiography, and all patients had postoperative cardiopulmonary examinations. One patient (1%) had a bilateral pneumothorax, which was detected clinically and confirmed by a chest radiograph. Five patients had postoperative pulmonary edema confirmed by clinical examination and radiography. Additional minor complications were noted, including minor bleeding and stomal infection, for an overall complication rate of 13%. CONCLUSIONS: All postoperative pulmonary complications were detected by physical examination. Therefore routine postoperative chest radiographs in uncomplicated tracheotomies are not necessary if a thorough postoperative cardiopulmonary examination is performed. Cost analysis reveals a savings of approximately $19,000 with the proposed criteria for postoperative chest x-ray.

Adult↗

PubMed1998

Close or positive margins after surgical resection for the head and neck cancer patient: the addition of brachytherapy improves local control.

PURPOSE: Microscopically positive or close margins after surgical resection results in an approximately 21-26% local failure rate despite excellent postoperative external radiation therapy. We sought to demonstrate improved local control in head and neck cancer patients who had a resection with curative intent, and had unexpected, microscopically positive or close surgical margins. METHODS AND MATERIALS: Twenty-nine patients with microscopically close or positive margins after curative surgery were given definitive, adjuvant external radiation therapy and 125I brachytherapy. All 29 patients had squamous cell cancer and tonsil was the most common subsite within the head and neck region. After external radiation therapy and thorough discussions with the attending surgeon and pathologists, the slides, gross specimens, and appropriate radiographs were reviewed and a target volume was determined. The target volume was the region of the margin in question and varied in size based on the surgery and pathologic results. Once the target volume was identified the patient was taken back to the operating room for insertion of 125I seeds. Activity implanted (range 2.9-21.5 millicuries) was designed to administer a cumulative lifetime dose of 120-160 Gy. RESULTS: Twenty-nine patients were followed for a median of 26 months (range 5-86 months). Two-year actuarial local control was 92%. CONCLUSION: 125I, after external radiation therapy, is an excellent method to improve local control in the subset of patients with unexpectedly unsatisfactory margins.

Brachytherapy↗

PubMed1998

A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck.

BACKGROUND: Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was initiated to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of HU in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck. METHODS: Patients were required to have histologically-documented and radiographically-staged locally advanced SCC of the hypopharynx (AJC stages II, III or IV), oropharynx (AJC stage IV), or oral cavity (AJC stage IV) not amenable to reasonable surgical resection. Eligible patients had adequate bone marrow, hepatic, and renal function and had to give informed consent. Concomitant, hyperfractionated, accelerated radiation therapy (CHRT) consisted of 1.2 Gy BID (6 hour minimum interfraction interval) on weekdays and 1.2 Gy delivered daily on the weekends to a total tumor dose of 74.4 Gy. Continuous infusion hydroxyurea (CHU) was administered at 0.25-0.375 mg/m2/min as a continuous intravenous infusion daily for 5 days with weekends days off for the duration of the radiation therapy. The dose of HU was increased by 0.125 mg/m2/min between dose levels until DLT was reached in 2/6 patients. If the primary had a complete clinical response and biopsies were negative, planned neck dissections were performed. RESULTS: Fifteen patients were enrolled and are evaluable. The initial dose level, 0.25 mg/m2/min was tolerated by 3/3 patients. At 0.375 mg/m2/min, 3/6 patients experienced grade 3-4 infections, with one patient having a non-fatal, subendocardial infarction. At 0.313 mg/m2/min, no patient experienced DLT. CONCLUSION: The MTD for CHU-CHRT was 0.313 mg/m2/min. The toxicities were primarily mucosal and a phase II study is in progress.

Adult↗

PubMed1997

Dissimilatory nitrate reduction in anaerobic sediments leading to river nitrite accumulation.

Recent studies on Northern Ireland rivers have shown that summer nitrite (NO(inf2)(sup-)) concentrations greatly exceed the European Union guideline of 3 (mu)g of N liter(sup-1) for rivers supporting salmonid fisheries. In fast-flowing aerobic small streams, NO(inf2)(sup-) is thought to originate from nitrification, due to the retardation of Nitrobacter strains by the presence of free ammonia. Multiple regression analyses of NO(inf2)(sup-) concentrations against water quality variables of the six major rivers of the Lough Neagh catchment in Northern Ireland, however, suggested that the high NO(inf2)(sup-) concentrations found in the summer under warm, slow-flow conditions may result from the reduction of NO(inf3)(sup-). This hypothesis was supported by field observations of weekly changes in N species. Here, reduction of NO(inf3)(sup-) was observed to occur simultaneously with elevation of NO(inf2)(sup-) levels and subsequently NH(inf4)(sup+) levels, indicating that dissimilatory NO(inf3)(sup-) reduction to NH(inf4)(sup+) (DNRA) performed by fermentative bacteria (e.g., Aeromonas and Vibrio spp.) is responsible for NO(inf2)(sup-) accumulation in these large rivers. Mechanistic studies in which (sup15)N-labelled NO(inf3)(sup-) in sediment extracts was used provided further support for this hypothesis. Maximal concentrations of NO(inf2)(sup-) accumulation (up to 1.4 mg of N liter(sup-1)) were found in sediments deeper than 6 cm associated with a high concentration of metabolizable carbon and anaerobic conditions. The (sup15)N enrichment of the NO(inf2)(sup-) was comparable to that of the NO(inf3)(sup-) pool, indicating that the NO(inf2)(sup-) was predominantly NO(inf3)(sup-) derived. There is evidence which suggests that the high NO(inf2)(sup-) concentrations observed arose from the inhibition of the DNRA NO(inf2)(sup-) reductase system by NO(inf3)(sup-).

Journal Article↗

PubMed1997

Reversible sensorineural hearing loss after renal transplant immunosuppression with OKT3 (muromonab-CD3).

Reversible and irreversible ototoxicity has been documented following the administration of various therapeutic agents. Reversible hearing loss is a known complication following the administration of quinine, salicylates and other nonsteroidal anti-inflammatory drugs, and erythromycin. We report a case of reversible hearing loss following OKT3 (murine monoclonal antibody CD3) administration. OKT3, a monoclonal antibody used as an immunosuppressant following cadaveric renal transplants, was associated with a transient sensorineural hearing loss that reversed following discontinuation of OKT3.

Adult↗