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Biomedical subjects

D L Cooper

Publications and source records attributed to D L Cooper.

At least 19 recordsLinked to original sources
PubMed2006

Can syndromic surveillance data detect local outbreaks of communicable disease? A model using a historical cryptosporidiosis outbreak.

A national UK surveillance system currently uses data from a health helpline (NHS Direct) in an attempt to provide early warning of a bio-terrorist attack, or an outbreak caused by a more common infection. To test this syndromic surveillance system we superimposed data from a historical outbreak of cryptosporidiosis onto a statistical model of NHS Direct call data. We modelled whether calls about diarrhoea (a proxy for cryptosporidiosis) exceeded a statistical threshold, thus alerting the surveillance team to the outbreak. On the date that the public health team were first notified of the outbreak our model predicted a 4% chance of detection when we assumed that one-twentieth of cryptosporidiosis cases telephoned the helpline. This rose to a 72% chance when we assumed nine-tenths of cases telephoned. The NHS Direct surveillance system is currently unlikely to detect an event similar to the cryptosporidiosis outbreak used here and may be most suited to detecting more widespread rises in syndromes in the community, as previously demonstrated. However, the expected rise in NHS Direct call rates, should improve early warning of outbreaks using call data.

Communicable Disease Control↗
PubMed2004

Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up.

PURPOSE: The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. PATIENTS AND METHODS: Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. RESULTS: Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. CONCLUSION: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.

Adolescent↗
PubMed2004

Target isotope effects for vibrationally-resolved electron capture in low-energy collisions of O3+ with molecular hydrogen.

Using a quantum-mechanical molecular-orbital coupled-channel (QMOCC) approach, we investigate single electron capture in collisions of O3+ with various molecular hydrogen isotopomers (H2, HD, T2) for collision energies of 1 and 100 eV u(-1). Potential energy surfaces and nonadiabatic couplings obtained with the spin-coupled valence-bond method are incorporated into QMOCC calculations of vibrationally-resolved cross sections of the product molecular ion. The infinite order sudden approximation is adopted and comparisons of the vibrational distributions are made with the centroid approximation, which incorporates ionization Franck-Condon factors. Intercomparison of the results is used to assess the reliability of the approximations and to give insight into the target isotope effects.

Journal Article↗
PubMed2003

Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma.

A high incidence of nonrelapse mortality (NRM) has limited the use of allogeneic transplantation for poor prognosis non-Hodgkin's lymphoma (NHL). We sought to improve the outcome of allografting by utilizing Filgrastim-mobilized peripheral blood stem cells (PBSC) in combination with either standard ablative or reduced-intensity conditioning. A total of 21 patients with intermediate/high-grade lymphoma and seven patients with low-grade histology were enrolled on protocols using PBSC. All patients were considered high risk for recurrence and/or NRM because of age >50 (n=16), refractory disease (n=17), failed autologous transplant (n=11) and abnormal organ function (n=2). In all, 17 patients received ablative regimens and 11 received modified conditioning including fludarabine, intravenous busulfan and ATG. Tacrolimus and mini-dose methotrexate were used for graft-versus-host-disease (GVHD) prophylaxis. Median follow-up was 38 months. Disease-free and overall survival were 57 and 58%. Seven of the 11 patients who relapsed after a previous transplant remain disease free. Four of the 10 patients with recurrent/persistent disease post transplant responded to additional therapy including withdrawal of immunosuppression+/-DLI. These results support a potent graft-versus-lymphoma effect and suggest that patients who relapse after an autologous transplant can be salvaged with an allogeneic transplant.

Adult↗
PubMed2003

A simplified approach to stem cell mobilization in multiple myeloma patients not previously treated with alkylating agents.

High-dose chemotherapy and autologous stem cell rescue is considered a standard part of initial therapy for patients with multiple myeloma. Therefore, potential transplant candidates are generally treated with dexamethasone-based programs rather than alkylating agents to avoid stem cell toxicity. The optimal mobilizing regimen for patients with multiple myeloma has not been defined. However, aggressive chemotherapy may result in excessive morbidity and cost in this older, immunocompromised population. We retrospectively examined our experience with a well-tolerated regimen of 1.5 g/m(2) cyclophosphamide on day -10 followed by 10 microg/kg G-CSF beginning on day -7 in 50 consecutive patients with multiple myeloma and no prior alkylating agent therapy. Median stem cell collection was 4.88 x 10(6) CD34+ cells/kg per apheresis and 44 patients collected >5 x 10(6) CD34+ cells/kg within 2 days. In 36 patients, more than 10 x 10(6) CD34+ cells/kg were collected including 33 patients who required 1-2 days of collection. One patient required hospitalization for fever/neutropenia and two required weekend apheresis. We conclude that 1.5 g/m(2) cyclophosphamide plus 10 microg/kg G-CSF is a safe, effective, highly predictable mobilizing program that uniformly provided enough stem cells for one transplant and enough stem cells for two transplants.

Adult↗
PubMed2003

What can analysis of calls to NHS direct tell us about the epidemiology of gastrointestinal infections in the community?

OBJECTIVES: Most gastrointestinal (GI) illness within the UK goes undetected by routine surveillance. A national telephone helpline for health advice (NHS Direct) offers a new source of data on GI infection. We aim to describe NHS Direct calls suggestive of GI infection and the outcome of these calls. METHODS: Details of over 150000 telephone calls were collected from NHS Direct over a 6-month period. Calls about 'diarrhoea', 'vomiting' or 'food poisoning' were defined as GI calls and described according to the age of the patient and call outcome. RESULTS: Gastrointestinal calls accounted for 10.3% of total calls ('diarrhoea'=4.9%, 'vomiting'=5.1%). GI calls as a proportion of total calls were significantly high in children under 1 year (23.5%) and aged 1-4 years (21.5%). Call outcomes which resulted in further NHS care being recommended accounted for 72.3% of total calls and 54.5% of GI calls. CONCLUSIONS: A high proportion of NHS Direct calls were about GI symptoms especially for children under 5 years. When compared with all NHS Direct calls, GI calls were less likely to result in further NHS care being recommended. Analysis of NHS Direct calls provides further insight into GI infection in the community.

Adolescent↗
PubMed2002

Use of NHS Direct calls for surveillance of influenza--a second year's experience.

A second year's call data to NHS Direct are presented to evaluate their usefulness for influenza surveillance. During the winter of 2000-01, age-group-specific data relating to the 'cold/flu' algorithm were collected from six NHS Direct sites (population coverage: 16 million). The total number of calls was collected from all 23 NHS Direct sites on a daily basis. Despite the winter of 2000-01 having been a season of low activity for influenza in the United Kingdom, NHS Direct data demonstrated a peak in the 'cold/flu' calls as a proportion of the total calls (3.1% [672 'cold/flu' calls] during week 06/01). This coincided with the peak recorded by routine influenza surveillance systems. There was also an earlier peak in the proportion of 'cold/flu' calls (3.3% during weeks 52/00 [789 'cold/flu' calls] and 01/01 [749 'cold/flu' calls]) which may have been due to other respiratory infections, the lack of specificity of the definition of NHS Direct 'cold/flu' calls and an increase in 'out-of-hours' calls to NHS Direct at the time. Despite limitations, the timeliness of NHS Direct data, the total population coverage of the service and the ability to provide local information on 'cold/flu' calls make the call data suitable for further surveillance during the winter of 2001-02. It is hoped that as NHS Direct reaches a 'steady state' in terms of population coverage and uniformity of clinical support systems, it will be possible to begin to construct 'baselines' for the respiratory disease related call data.

Adolescent↗
PubMed2001

Modern valence-bond description of chemical reaction mechanisms: the 1,3-dipolar addition of diazomethane to ethene.

The electronic mechanism for the gas-phase concerted 1,3-dipolar cycloaddition of diazomethane (CH2N2) to ethene (C2H4) is described through spin-coupled (SC) calculations at a sequence of geometries along the intrinsic reaction coordinate obtained at the MP2/6-31G(d) level of theory. It is shown that the bonding rearrangements occurring during the course of this reaction follow a heterolytic pattern, characterized by the movement of three well-identifiable orbital pairs, which are initially responsible for the pi bond in ethene and the C-N pi bond and one of the N-N pi bonds in diazomethane and are retained throughout the entire reaction path from reactants to product. Taken together with our previous SC study of the electronic mechanism of the 1,3-dipolar cycloaddition of fulminic acid (HCNO) to ethyne (C2H2) (Theor. Chim. Acc. 1998, 100, 222), the results of the present work suggest strongly that most gas-phase concerted 1,3-dipolar cycloaddition reactions can be expected to follow a heterolytic mechanism of this type, which does not involve an aromatic transition state. The more conventional aspects of the gas-phase concerted 1,3-dipolar cycloaddition of diazomethane to ethene, including optimized transition structure geometry, electronic activation energy, activation barrier corrected for zero-point energies, standard enthalpy, entropy and Gibbs free energy of activation, have been calculated at the HF/6-31G(d), B3LYP/6-31G(d), MP2/6-31G(d), MP2/6-31G(d,p), QCISD/6-31G(d) and CCD/6-31G(d) levels of theory. We also report the CCD/6-311++G(2d, 2p)//CCD/6-31G(d), MP4(SDTQ)/6-311++G(2d,2p)//CCD/6-31G(d) and CCSD(T)/6-311++G(2d, 2p)//CCD/6-31G(d) electronic activation energies.

Journal Article↗
PubMed2001

Phase II trial of 9-aminocamptothecin as a 72-h infusion in cutaneous T-cell lymphoma.

PURPOSE: To evaluate the role of 9-aminocamptothecin (9-AC), a synthetic camptothecin analog, in advanced cutaneous T-cell lymphoma (CTCL). METHODS: Eligible patients had stage IIB-IV CTCL. 9-AC was infused over 72 h at a dose of 1,100 microg/m2 per day (approximately 46 microg/m2/h) every 2 weeks, with granulocyte-colony stimulating factor (G-CSF) support. RESULTS: Twelve patients received a total of 30 cycles of 9-AC. Nine patients had stage IV disease, 5 patients had circulating Sezary cells, and 2 patients had evidence of tranformation to a large cell lymphoma. Most of the patients were heavily pretreated: 10 had received prior chemotherapy (83%), 5 of whom had received 2 or more prior regimens, including a patient who had received high-dose chemotherapy, and 7 had previously received total-skin electron beam therapy. The study was prematurely terminated due to substantial toxicity. Six patients (50%) developed an indwelling central venous catheter-related infection, 5 during a period of neutropenia. Three patients died due to sepsis 4-8 weeks after their last 9-AC treatment. Two of these patients had a previous history of bacterial sepsis. Four patients (33%) developed grade IV thrombocytopenia. Two partial responses were observed (response rate 17%), but the duration of response was brief, 4-8 weeks. CONCLUSION: 9-AC at this schedule and route of administration had activity but resulted in an unacceptable rate of complicated neutropenia and septic deaths in heavily pretreated patients with advanced CTCL who are susceptible to catheter-related infections.

Adult↗
PubMed2000

High-dose BEAM chemotherapy with autologous peripheral blood progenitor-cell transplantation for unselected patients with primary refractory or relapsed Hodgkin's disease.

BACKGROUND: The use of autologous peripheral blood progenitor cells (PBPC) expedites hematologic recovery and reduces the costs of transplantation in comparison with autologous bone marrow; however, its efficacy in patients with Hodgkin's disease has been questioned. We evaluated the results of autologous PBPC transplantation in a population of unselected and uniformly treated patients with primary refractory or relapsed Hodgkin's disease. PATIENTS AND METHODS: Forty consecutive adult patients with primary refractory (n = 7) or relapsed (n = 33) Hodgkin's disease received high-dose BEAM (BCNU, etoposide, ara-C, and melphalan) followed by autologous PBPC infusion. Twenty-four patients (60%) received high-dose BEAM as outpatients. Consolidative radiation therapy was administered to 14 patients (35%). RESULTS: Thirty-seven patients (92%) achieved a post transplant complete response. The 3-year progression-free survival (PFS) was 69%, and the 3-year overall survival (OS) was 77%, with a median follow-up of surviving patients of 28 months. Severe non-hematologic toxicities included gastrointestinal side effects (diarrhea 17%, mucositis 25%), and interstitial pneumonitis (15%). One patient died of acute transplant-related complications (mortality rate 2.5%). Strong predictors of poor PFS were chemoresistant versus chemosensitive/untested disease (actuarial PFS 89% versus 22%, P = 0.0000) and stage IIB-IV versus I-IIA at relapse/progression (86%, versus 46%, P = 0.005). All five patients with elevated lactate dehydrogenase at the time of transplantation died of their disease. There was a trend toward worse PFS for patients receiving a higher number of CD34+ cells (> or = 11 x 10(6) per kg). CONCLUSIONS: High-dose BEAM chemotherapy with autologous PBPC transplantation is associated with low mortality and results in satisfactory PFS for patients with primary refractory or relapsed Hodgkin's disease. The subset of patients with progressive disease at the time of transplantation performs poorly and may benefit from alternative strategies.

Adolescent↗
PubMed2000

In vitro collection and posttransfusion engraftment characteristics of MNCs obtained by using a new separator for autologous PBPC transplantation.

BACKGROUND: A clinical study was performed to evaluate the peripheral blood progenitor cell (PBPC) collection, transfusion, and engraftment characteristics associated with use of a blood cell separator (Amicus, Baxter Healthcare). STUDY DESIGN AND METHODS: Oncology patients (n = 31) scheduled for an autologous PBPC transplant following myeloablative therapy were studied. PBPCs were mobilized by a variety of chemotherapeutic regimens and the use of G-CSF. As no prior studies evaluated whether PBPCs collected on the Amicus separator would be viable after transfusion, to ensure patient safety, PBPCs were first collected on another cell separator (CS-3000 Plus, Baxter) and stored as backup. The day after the CS-3000 Plus collections were completed, PBPC collections intended for transfusion were performed using the Amicus instrument. For each transplant, >2.5 x 10(6) CD34+ PBPCs per kg of body weight were transfused. RESULTS: Clinical data collected on the donors immediately before and after PBPC collection with the Amicus device were comparable to donor data similarly obtained for the CS-3000 Plus collections. While the number of CD34+ cells and the RBC volume in the collected products were equivalent for the two devices, the platelet content of the Amicus collections was significantly lower than that of the CS-3000 Plus collections (4.35 x 10(10) platelets/bag vs. 6.61 x 10(10) platelets/bag, p<0.05). Collection efficiencies for CD34+ cells were 64 +/- 23 percent for the Amicus device and 43 +/- 14 percent for the CS-3000 Plus device (p<0.05). The mean time to engraftment for cells collected via the Amicus device was 8.7 +/- 0.7 days for >500 PMNs per microL and 9.7 +/- 1.5 days to attain a platelet count of >20,000 per microL-equivalent to data in the literature. No CS-3000 Plus backup cells were transfused and no serious adverse events attributable to the Amicus device were encountered. CONCLUSIONS: The mean Amicus CD34+ cell collection efficiency was better (p<0.05) than that of the CS-3000 Plus collection. Short-term engraftment was durable. The PBPCs collected with the Amicus separator are safe and effective for use for autologous transplant patients requiring PBPC rescue from high-dose myeloablative chemotherapy.

Adolescent↗
PubMed2000

P-glycoprotein expression and multidrug resistance in cutaneous T-cell lymphoma.

Advanced-stage cutaneous T-cell lymphoma (CTCL) is generally resistant to standard chemotherapy. Because P-glycoprotein (P-gp) has been detected in other types of resistant solid tumors, leukemias, and lymphomas, we analyzed P-gp expression in CTCL. Twenty-seven patients with CTCL and circulating Sezary cells in the peripheral blood as observed on a peripheral smear treated at the Yale Photopheresis Center between 1987 and 1993 were identified. Twenty-five of these patients had skin biopsies evaluated for expression of P-gp using JSB-1 (Accurate Chemical), MRK-16 (gift of T. Tsuruo), and UIC-2 (gift of E. Metchner). P-gp expression was considered present if immunoreactivity was noted with two of the three antibodies. Eighteen of 25 patients (72%) evaluated exhibited expression. The patients were treated with various combinations of drugs consisting of topical and systemic steroids electron beam therapy, psoralens in combination with UV light A (PUVA), systemic chemotherapy, and photopheresis before testing the tissue for P-gp expression. Treatment with systemic chemotherapy in P-gp-positive patients produced responses in 3 and no responses in 11 patients (4 were lost to follow-up). Seven patients did not express P-gp: One patient responded to treatment, five did not respond, and one patient was lost to follow-up. These results demonstrate that P-gp is frequently expressed in CTCL. P-gp expression in our study was not a useful predictor of drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44.

Correlations have been noted between the expression of certain alternatively spliced CD44 isoforms and the metastatic propensity of various histologically distinct tumor cell types. The precise mechanism by which particular CD44 isoforms contribute to the metastatic process is, however, unclear. In the present study we demonstrate that CD44R2, a CD44 isoform highly expressed on activated and transformed hemopoietic cells, can recognize and bind a common determinant present on CD44H and CD44R1. Importantly, CD44H lacked this activity. Pretreatment of TIL1 cells expressing CD44H or CD44R1 with chondroitinase ABC inhibited adhesion to CD44R2, suggesting that the unique inserted region present within the CD44R2 molecule, encoded by exon v10, mediates cell adhesion by potentiating the recognition of chondroitin sulfate moieties presented in association with other CD44 molecules. These data help explain the differential involvement of v10-containing CD44 isoforms in tumor metastasis.

Adjuvants, Immunologic↗
PubMed1999

Differential expressions of CD44 variants in tumors affecting the central nervous system.

BACKGROUND: The polymorphic cell adhesion molecule CD44 exists as a family of proteins generated by extensive alternative splicing of the CD44 pre-messenger RNA and marked posttranslational modification. The differential expression of CD44 isoforms in a variety of human cancers has been proposed to influence tumorigenesis and metastasis. In this study, CD44 gene expression was analyzed in primary and metastatic tumors and in cell lines derived from tumors that affect the central nervous system (CNS), including tumors metastatic to the spine. MATERIALS AND METHODS: Fifty-four samples were subjected to semiquantitative reverse-transcriptase polymerase chain reaction with CD44-specific primers and hybridized individually with probes specific for the CD44 variant (CD44v) exons v3 to v10. RESULTS: Compared with CD44v-positive breast cancer cell lines and CD44v-negative normal brain tissue, CD44v expression was weak in primary brain tumors and cell lines derived from normal brain and tumor tissue. However, high levels of isoforms encoding multiple-variant exons were shown in all metastatic brain tumors. In contrast, tumors metastatic to the spine were virtually negative for CD44v expression. Several rare CD44 isoforms composed of single-variant exons v3, v4, v6, or v9 were identified in primary brain tumors and may reflect their invasive potential or culturability in vitro. CONCLUSION: These data suggest differential expression of CD44v may substantially influence the end-organ site of metastasis for tumor cells destined for the CNS.

Antigens, Neoplasm↗