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Biomedical subjects

Seth Cohen

Publications and source records attributed to Seth Cohen.

14 recordsLinked to original sources
PubMed2007

Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy.

OBJECTIVE: Intratympanic steroids are increasingly used in the treatment of inner ear disorders, especially in patients with sudden sensorineural hearing loss (SNHL) who have failed systemic therapy. We reviewed our experience with intratympanic steroids in the treatment of patients with sudden SNHL to determine overall success, morbidity, and prognostic factors. HYPOTHESIS: Intratympanic steroids have minimal morbidity and the potential to have a positive effect on hearing recovery in patients with sudden SNHL who have failed systemic therapy. STUDY DESIGN: The authors conducted a retrospective review. METHODS: Patients presenting with sudden SNHL defined as a rapid decline in hearing over 3 days or less affecting 3 or more frequencies by 30 dB or greater who underwent intratympanic steroids therapy (24 mg/mL dexamethasone) were reviewed. Excluded were patients with Meniere disease, retrocochlear disease, autoimmune HL, trauma, fluctuating HL, radiation-induced HL, noise-induced HL, or any other identifiable etiology for sudden HL. Patients who showed signs of fluctuation of hearing after injection were excluded. Pretreatment and posttreatment audiometric evaluations including pure-tone average (PTA) and speech reception threshold (SRT) were analyzed. Patient variables as they related to recovery were studied and included patient age, time to onset of therapy, status of the contralateral ear, presence of diabetes, severity of HL, and presence of associated symptoms (tinnitus, vertigo). A 20-dB gain in PTA or a 20% improvement in SDS was considered significant. RESULTS: : Forty patients fit the criteria for inclusion in the study. The mean age of the patients was 54.8 years with a range from 17 to 84 years of age. Overall, 40% (n = 16) showed any improvement in PTA or SDS. Fourteen (35%) men and 26 (65%) women were included. Using the criteria of 20-dB improvement in PTA or 20% improvement in SDS for success, 27.5% (n = 11) showed improvement. The mean number of days from onset of symptoms to intratympanic therapy was 40 days with a range of 7 days to 310 days. A statistically significant difference was noted in those patients who received earlier injection (P = .0008, rank sum test). No patient receiving intratympanic dexamethasone after 36 days recovered hearing using 20-dB PTA decrease or a 20% increase in discrimination as criteria for recovery. Twelve percent (n = 5) of patients in the study had diabetes with 20% recovering after intratympanic dexamethasone (not significantly different from nondiabetics at 28.6%, Fisher exact test, P = 1.0). Comparison to other studies that used differing steroid type, concentration, dosing schedule, inclusion criteria, and criteria for success revealed, in many instances, a similar overall recovery rate. CONCLUSIONS: Difficulty in proving efficacy of a single modality is present in all studies on SNHL secondary to multiple treatment protocols, variable rates of recovery, and a high rate of spontaneous recovery. Forty percent of patients showed some improvement in SDS or PTA after treatment failure. When criteria of 20-dB PTA or 20% is considered to define improvement, the recovery rate was 27.5%. Modest improvement is seen with the current protocol of a single intratympanic steroid injection of 24 mg/mL dexamethasone in patients who failed systemic therapy. Dramatic hearing recovery in treatment failures was rarely encountered. No patient showed significant benefit from intratympanic steroids after 36 days when using this protocol for idiopathic sudden SNHL. If patients injected after 6 weeks are excluded from the study, the improvement rate increases from 26.9% to 39.3%. Earlier intratympanic injection had a significant impact on hearing recovery, although with any therapeutic intervention for sudden SNHL, early success may be attributed to natural history. If we further exclude seven patients treated with intratympanic steroids within 2 weeks of the onset of symptoms (i.e., study only those patients treated with intratympanic dexamethasone between 2 and 6 weeks after onset of symptoms), still, 26% improved by 20 dB or 20% SDS. The recovery rates after initial systemic failure are higher than would be expected in this treatment failure group given our control group (9.1%) and literature review. These findings indicate a positive effect from steroid perfusion in this patient population.

Adolescent↗
PubMed2006

Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma.

PURPOSE: To characterize the number and functional status of CD4+CD25+ regulatory T cells (Tregs) in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) treated with high-dose bolus interleukin-2 (IL-2). PATIENTS AND METHODS: Patients with MM or RCC treated with high-dose bolus IL-2 (600,000 IU/kg every 8 hours) at a single center provided pre- and post-treatment whole blood specimens. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, separated into cellular subsets, and analyzed by flow cytometry or used for in vitro proliferation assays. RESULTS: Between September 2003 and July 2005 57 patients were enrolled in the study with 48 patients available for analysis (45 MM, 12 RCC). Tregs were defined as CD4+CD25(hi) T cells, and this subset was significantly elevated in the cancer patients compared with normal donors (7.75% v 2.24%). The CD4(+)CD25(hi) T-cell pool in the patients constitutively expressed intracellular FoxP3, CTLA-4, and produced high amounts of IL-10. The Tregs were CCR7+ with 50% representing naïve and 50% central-memory T cells. The cells were functionally suppressive in mixed in vitro proliferation assays. Following IL-2 administration, the number and frequency of Tregs increased in patients with progressive disease but returned to normal levels in patients with objective clinical responses. CONCLUSION: The number of Tregs, defined as CD4+CD25(hi) T cells is increased in patients with MM and RCC. High-dose IL-2 resulted in a significant decrease of Tregs in those patients achieving an objective clinical response to IL-2 therapy.

Adult↗
PubMed2006

Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors.

Successful immunotherapy of established tumors depends on overcoming the suppressive influence of the local tumor microenvironment. The direct injection of vaccinia virus expressing the B7.1 (CD80) costimulatory molecule into melanoma lesions resulted in local and systemic immunity with associated clinical responses. Therefore, we sought to evaluate the effects of a vaccinia virus expressing three costimulatory molecules, B7.1, ICAM-1, and LFA-3 (rV-TRICOM), in patients with metastatic melanoma. A standard dose escalation phase I clinical trial was performed. Thirteen patients were enrolled and 12 were available for follow-up. Local vaccination was feasible, with only low-grade injection site reactions associated with mild fatigue and myalgia reported. There was one occurrence of grade 1 vitiligo. Overall there was a 30.7% objective clinical response, with one patient achieving a complete response for more than 22 months. An inverse association was detected between anti-vaccinia antibody and anti-vaccinia T cell responses. Patients who failed to respond to vaccination but received high-dose interleukin-2 had a trend toward improved survival. Collectively, these results confirm the safety profile and feasibility of direct injection of vaccinia virus expressing multiple costimulatory molecules in patients with established tumors. Further clinical investigation is needed to better define the role of antigen, adjuvant cytokines, costimulation, and cross-presentation in the host immune response to local vaccination with vaccinia viruses expressing immunomodulatory molecules.

Adult↗
PubMed2006

Identification of Cpgp40/15 Type Ib as the predominant allele in isolates of Cryptosporidium spp. from a waterborne outbreak of gastroenteritis in South Burgundy, France.

Cryptosporidium sp. isolates from a waterborne outbreak of diarrhea in France were analyzed by PCR-restriction fragment length polymorphism analysis and sequencing of the Cpgp40/15 locus. Ninety-one percent of the isolates were Cryptosporidium hominis type Ib. The results of this study and those of studies of other outbreaks suggest that the type Ib allele is the predominant allele associated with waterborne cryptosporidiosis.

Alleles↗
PubMed2005

An early intestinal mucosal source of gamma interferon is associated with resistance to and control of Cryptosporidium parvum infection in mice.

Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-gamma) dependent. Using an IFN-gamma-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-gamma and demonstrate that CD8+ T-cell receptor alphabeta intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-gamma expression and secretion by naive CD8+ T cells in response to a protozoan pathogen have not previously been demonstrated.

Animals↗
PubMed2004

TG-4010 Transgene.

Transgene is developing TG-4010, a second-generation modified vaccinia virus Ankara encoding MUC1 and interleukin-2 for the potential treatment of a variety of cancer types. Phase II trials are underway for non-small-cell lung cancer, metastatic renal cancer and prostate cancer.

Animals↗
PubMed2003

Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation.

BACKGROUND: Atypical antipsychotics effectively reduce maladaptive behavior in individuals with mental retardation, yet bring significant weight gain and metabolic anomalies. Ziprasidone, a weight-neutral antipsychotic in patients with schizophrenia or schizoaffective disorder, has not been studied in a population with mental retardation and maladaptive behaviors. METHOD: Forty patients with mental retardation and maladaptive behaviors who had gained excessive weight or were inadequately responsive to other agents were switched to ziprasidone. Weight, total cholesterol, HDL, LDL, triglycerides, and frequency of maladaptive behavior were recorded at baseline and after 6 months of ziprasidone treatment. RESULTS: Ziprasidone treatment was associated with a significant weight loss of 8.1 lb (3.6 kg) as well as a significant reduction in total cholesterol and triglycerides (p < or =.05). The monthly frequency of the maladaptive behavior remained unchanged or improved in 72% (18/25) of the patients in whom maladaptive behavior was assessed. CONCLUSION: Ziprasidone effectively reduces the frequency of maladaptive behavior in a patient group with mental retardation without causing weight gain or metabolic disturbances.

Antipsychotic Agents↗
PubMed2002

Surgery and cancer of the pancreas: will common sense become common practice?

Pancreatic cancer is a systemic disease for most patients. Operations with the intent to cure may be done safely (mortality, < 3%) with shorter hospital stays. Surgery has been minimally effective as a long-term cure. Endoscopic palliation of jaundice is becoming standard practice. Common sense dictates a defined and clear role for surgery (i.e., strict patient selection criteria). Surgery is of great value for small, localized lesions; of clear value as palliative therapy when nonoperative measures fail; and perhaps best applied after neoadjuvant chemoradiotherapy. Surgery is just part of the armamentarium available to treat pancreatic cancer. Novel systemic therapies, including chemotherapy, immunotherapy, and so-called targeted therapies, are becoming increasingly valuable in the management of this systemic disease and are discussed in detail in other articles in this issue.

Adenocarcinoma↗
PubMed2002

"Tannenbaum" Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture.

BACKGROUND: Premature stent clogging is the major limitation with plastic stents used in the treatment of malignant biliary structures. A pilot study suggested improved duration of patency of the Tannenbaum stent compared with polyethylene stents. The aim of this prospective, multicenter randomized trial was to compare the Tannenbaum Teflon stent with a conventional polyethylene endoprosthesis (Cotton-Leung biliary stent set) for the treatment of malignant biliary strictures. METHODS: Patients over age 18 years with symptoms caused by nonhilar malignant biliary strictures were enrolled. Patients were randomized to receive a 10F Tannenbaum or polyethylene stent after a guidewire was passed beyond the stricture. One hundred six patients (mean age 72 years and 71 years, respectively) were enrolled (54 Tannenbaum, mean age 72 years; 52 polyethylene, mean age 71 years). RESULTS: Tannenbaum and polyethylene stent placement was successful in, respectively, 100% and 96% of procedures without complications. The mean (SD) 90-day stent patency of the Tannenbaum stent was 67% (7%) compared with 73% (7%) for the polyethylene stents. CONCLUSIONS: The present study demonstrated no difference in ease of implantation or stent patency between Tannenbaum and polyethylene stents.

Aged↗
PubMed2002

Fully automated screening systems.

A fully automated system is one of the most valuable tools available for HTS. However, proper sourcing, installation and operation of an automated system requires a thorough inventory of your needs and a strong attention to detail in the implementation and operation. As you could see from the examples, assays can usually be transferred to an automated robotic system with minimum changes. However details must be reviewed to assure that the results will be consistent within a run and as compared to the same assay performed manually on the bench or on workstations. Validation is a crucial element to assure that the integrated system and the individual components are operating within their designated tolerances.

Automation↗
PubMed2002

A pathway-specific cell based screening system to detect bacterial cell wall inhibitors.

A pathway-specific cell-based screen is described to detect compounds that inhibit the biosynthesis of the cell wall of bacteria. The basis for detection is the discovery that the beta-lactamase gene from Citrobacterfreundii, cloned into Escherichia coli, is induced when cells are exposed to known cell wall inhibitors, and not just beta-lactam-based antibiotics. In a wild type host, cell wall inhibitors such as moenomycin, vancomycin, and ramoplanin, which are excluded by the outer membrane, only induce at high concentrations. However, these compounds, as well as fosfomycin, cycloserine, and cefoxitin, induce at concentrations at or below the MIC of a host carrying the envA-mutation, which causes a defect in the outer membrane. As additional proof that induction of beta-lactamase is the direct result of cell wall inhibition, a host strain carrying a temperature-sensitive mutation in the murG gene, whose product converts the cell wall intermediate Lipid I, to Lipid II, also induced beta-lactamase at the restrictive temperature. A protocol is described for screening samples in high-throughput mode.

Anti-Bacterial Agents↗
PubMed2002

Identification of compounds that inhibit late steps of peptidoglycan synthesis in bacteria.

A screening system is described that can detect and confirm inhibitors of the late steps of cell wall biosynthesis. The primary high through-put screen monitors induction of beta-lactamase following exposure to samples, in an Escherichia coli envA- strain that carries the beta-lactamase gene from Citrobacter freundii on a plasmid. Positive samples were detected from compound libraries, from natural products libraries, and from fractions of natural products crude preparations. These samples were then subjected to in vitro assays that could detect the incorporation of soluble cell wall precursor into Lipid I, Lipid II, and polymerized cell wall, using a TLC system that was very accurate and unambiguous in detecting known cell wall inhibitors. One partially purified sample containing a novel antibacterial agent derived from natural products was found to inhibit the formation of Lipid I (50% inhibition at < or = 62.5 ng/ml), whereas another partially purified sample also derived from natural products inhibited transglycosylation into cell wall polymer (50% inhibition at < or = 10 microg/ml). This screening system proved to be especially useful because it was sufficiently sensitive and robust to detect inhibitors among samples of crude preparations or varying states of purity.

Anti-Bacterial Agents↗
PubMed1987

Treatment Options in Severe Psychotic Depression.

In our sample of 15 hospitalized patients with severe psychotic depression, six responded to therapy with tricyclic antidepressants combined with neuroleptics. Of the nine nonresponders, eight showed an excellent clinical response to electroconvulsive therapy (ECT). The clinical outcome after 6 months of treatment was similar in both groups. We recommend that protracted, complicated trials of pharmacotherapy be reevaluated in psychotic depression. A prospective comparative study of ECT and pharmacotherapy is needed to define the optimal treatment for psychotic depression.

Journal Article↗