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R L Edwards

Publications and source records attributed to R L Edwards.

At least 19 recordsLinked to original sources
PubMed2002

Direct determination of the timing of sea level change during termination II.

An outcrop within the last interglacial terrace on Barbados contains corals that grew during the penultimate deglaciation, or Termination II. We used combined 230Th and 231Pa dating to determine that they grew 135.8 +/- 0.8 thousand years ago, indicating that sea level was 18 +/- 3 meters below present sea level at the time. This suggests that sea level had risen to within 20% of its peak last-interglacial value by 136 thousand years ago, in conflict with Milankovitch theory predictions. Orbital forcing may have played a role in the deglaciation, as may have isostatic adjustments due to large ice sheets. Other corals in the same outcrop grew during oxygen isotope (delta18O) substage 6e, indicating that sea level was 38 +/- 5 meters below present sea level, about 168.0 thousand years ago. When compared to the delta18O signal in the benthic V19-30/V19-28 record at that time, the coral data extend to the previous glacial cycle the conclusion that deep-water temperatures were colder during glacial periods.

Animals↗
PubMed2001

A high-resolution absolute-dated late Pleistocene Monsoon record from Hulu Cave, China.

Oxygen isotope records of five stalagmites from Hulu Cave near Nanjing bear a remarkable resemblance to oxygen isotope records from Greenland ice cores, suggesting that East Asian Monsoon intensity changed in concert with Greenland temperature between 11,000 and 75,000 years before the present (yr. B.P.). Between 11,000 and 30,000 yr. B.P., the timing of changes in the monsoon, as established with 230Th dates, generally agrees with the timing of temperature changes from the Greenland Ice Sheet Project Two (GISP2) core, which supports GISP2's chronology in this interval. Our record links North Atlantic climate with the meridional transport of heat and moisture from the warmest part of the ocean where the summer East Asian Monsoon originates.

Journal Article↗
PubMed2001

Extremely large variations of atmospheric 14C concentration during the last glacial period.

A long record of atmospheric 14C concentration, from 45 to 11 thousand years ago (ka), was obtained from a stalagmite with thermal-ionization mass-spectrometric 230Th and accelerator mass-spectrometric 14C measurements. This record reveals highly elevated Delta14C between 45 and 33 ka, portions of which may correlate with peaks in cosmogenic 36Cl and 10Be isotopes observed in polar ice cores. Superimposed on this broad peak of Delta14C are several rapid excursions, the largest of which occurs between 44.3 and 43.3 ka. Between 26 and 11 ka, atmospheric Delta14C decreased from approximately 700 to approximately 100 per mil, modulated by numerous minor excursions. Carbon cycle models suggest that the major features of this record cannot be produced with solar or terrestrial magnetic field modulation alone but also require substantial fluctuations in the carbon cycle.

Journal Article↗
PubMed2001

High-precision U-series dating of Locality 1 at Zhoukoudian, China.

Thermal ionization mass spectrometric(230)Th/(234)U dating has been carried out on intercalated speleothem samples from the limestone cave occupied by Homo erectus at Zhoukoudian, China. The samples were recently collected in proper stratigraphic context after detailed field examinations. The results show that the age of the No. 5 Skull from Layer 3 is >400 ka, possibly in the range of about 400-500 ka, and that the hominid fossils from the lower strata are at least 600 ka and possibly >800 ka, much older than previously thought. The near-equilibrium(230)Th/(234)U ratios and internal consistency of the dates and stratigraphy lend credence to the results and allow us to comment on their important implications for human evolution.

Animals↗
PubMed2001

Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation.

BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis. PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation. The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis. RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion. Each of these patients was neutropenic and presented with fever. Three isolates demonstrated intermediate resistance to macrolides in vitro. However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy. CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia. Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses.

Adolescent↗
PubMed2001

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.

Adult↗
PubMed2001

Cytoreduction and stem cell mobilization with a regimen of paclitaxel, etoposide and cyclophosphamide followed by autologous transplantation using a preparative regimen of busulfan, etoposide and cyclophosphamide for patients with advanced lymphoma.

Forty-one patients with advanced Hodgkin's disease or intermediate or high-grade lymphoma, after having received standard salvage chemotherapy, were treated with a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D-TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral blood stem cells. This regimen produced a response rate of 78% (35% complete and 43.2% partial response) and mobilized sufficient peripheral blood stem cells in 94% of the patients. Thirty-two of these patients then underwent autologous progenitor cell transplantation after ablative conditioning with busulfan, etoposide and cyclophosphamide. Actuarial overall survival at 61 months was 71.9% with an event-free survival (EFS) of 65.6%. Median EFS was 24.4 months. EFS of patients responsive to salvage chemotherapy was 75% at 61 months, compared to 33.3% at 51.4 months in patients resistant to salvage chemotherapy. EFS of patients with disease sensitive to D-TEC was 75% at 61 months compared to 0% at 13.1 months in patients resistant to D-TEC. In a multivariate analysis, the only significant parameter for transplant outcome was sensitivity to D-TEC (p = 0.016), but not sensitivity to standard salvage chemotherapy. Aggressive cytoreduction may permit even those patients who are resistant to standard salvage chemotherapy to become successful transplant candidates.

Adolescent↗
PubMed2001

Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation.

OBJECTIVE: To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT). CLINICAL FINDINGS: A total of 271 patients with a variety of underlying malignancies received busulfan-containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae. DISCUSSION: Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy. CONCLUSIONS: IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long-term pulmonary sequelae following early treatment with glucocorticoids.

Adolescent↗
PubMed2000

Early human occupation of the Red Sea coast of Eritrea during the last interglacial.

The geographical origin of modern humans is the subject of ongoing scientific debate. The 'multiregional evolution' hypothesis argues that modern humans evolved semi-independently in Europe, Asia and Africa between 100,000 and 40,000 years ago, whereas the 'out of Africa' hypothesis contends that modern humans evolved in Africa between 200 and 100 kyr ago, migrating to Eurasia at some later time. Direct palaeontological, archaeological and biological evidence is necessary to resolve this debate. Here we report the discovery of early Middle Stone Age artefacts in an emerged reef terrace on the Red Sea coast of Eritrea, which we date to the last interglacial (about 125 kyr ago) using U-Th mass spectrometry techniques on fossil corals. The geological setting of these artefacts shows that early humans occupied coastal areas and exploited near-shore marine food resources in East Africa by this time. Together with similar, tentatively dated discoveries from South Africa this is the earliest well-dated evidence for human adaptation to a coastal marine environment, heralding an expansion in the range and complexity of human behaviour from one end of Africa to the other. This new, wide-spread adaptive strategy may, in part, signal the onset of modern human behaviour, which supports an African origin for modern humans by 125 kyr ago.

Adaptation, Physiological↗
PubMed2000

Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 321 consecutive recipients of high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of vancomycin-resistant enterococcal (VRE) bacteremia. Ten patients developed VRE bacteremia at a median of 6 days following PBSCT. Nine isolates were Enterococcus faecium and one was E. faecalis. The median duration of bacteremia was 5 days. The central venous catheter was removed in seven individuals. Nine patients were treated with a variety of antimicrobial agents including quinupristin-dalfopristin, chloramphenicol, doxycycline, oral bacitracin, co-trimoxazole, and nitrofurantoin. Bacteremia resolved without adverse sequelae in seven patients. Two individuals who died of other causes had persistent or relapsed bacteremia at the time of death. An additional patient suffered multiple relapses of VRE bacteremia and died as a result of VRE endocarditis 605 days following PBSCT. Mortality as a direct result of VRE bacteremia was 10% in this series. The optimal type and duration of treatment of VRE bacteremia has not been clearly defined. Therefore, we perform weekly stool surveillance cultures for VRE in our hospitalized transplant population and apply strict barrier precautions in those individuals in whom stool colonization has been identified. Furthermore, the empiric use of vancomycin has been restricted. Bone Marrow Transplantation (2000) 25, 147-152.

Adolescent↗
PubMed2000

Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer.

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.

Antineoplastic Agents, Hormonal↗
PubMed2000

Kaposi's sarcoma following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia.

Unlike solid organ transplantation, Kaposi's sarcoma (KS) occurs rarely following hematopoietic stem cell transplantation (HSCT). In fact, only 5 cases of KS have been reported after allogeneic or autologous HSCT. The usual treatment combines a substantial decrease in, or elimination of, immunosuppressive therapy along with local measures such as surgical excision, cryotherapy or radiation therapy. A 46-year-old woman with chronic myelogenous leukemia who had received an allogeneic HSCT previously from an HLA-identical sibling, presented on day +814 with human herpes virus-8-associated KS involving her left lower extremity. She had been on continuous immunosuppressive therapy since her transplant because of chronic graft-versus-host disease. The intensity of immunosuppressive therapy was decreased once a diagnosis of KS had been established. However, the nodular lesions continued to progress in size and number. Therefore, a course of irradiation was administered to sites of bulk disease on her legs. Furthermore, thalidomide was initiated along with a topical retinoid, alitretinoin 0.1% gel applied twice daily to the nonirradiated lesions. This approach yielded a partial response in both irradiated and nonirradiated lesions over the course of the following 7 months. Both thalidomide and alitretinoin 0.1% gel appear to be beneficial in HSCT-associated KS and exhibit tolerable side effects.

Administration, Oral↗
PubMed1999

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue.

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.

Adult↗
PubMed1999

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.

Adolescent↗
PubMed1999

Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence, risk factors, clinical features, complications, and outcome of cytomegalovirus (CMV) infection. A total of 26 patients (13%) developed CMV viremia (n = 5), DNAemia (n = 3), viruria (n = 18) and/or disease (n = 3) at a median of 45 days following stem cell infusion. None of the patients underwent surveillance testing for CMV. A diagnosis was established by culture and polymerase chain reaction of blood, urine or other tissue samples submitted when patients exhibited clinical features suggestive of CMV infection. Cytomegalovirus seropositivity prior to transplantation was the only statistically significant risk factor predicting subsequent identification of CMV (P < 0.001). The symptoms were severe enough in 23 patients to warrant treatment with intravenous ganciclovir. Three patients developed CMV disease; two developed fatal CMV pneumonia and one developed CMV gastritis which responded to antiviral treatment. Clinical signs and symptoms as well as viremia and viruria resolved with (20 patients) and without (three patients) treatment in the remaining individuals. All instances of CMV viremia, DNAemia, viruria and disease occurred within 3 months of stem cell infusion. These results demonstrate that CMV is a common pathogen after autologous PBSCT and may result in fatality in rare instances. Surveillance programs appear to be neither useful nor cost-effective. Diagnostic evaluation should be performed only in patients exhibiting suspicious clinical features and antiviral chemotherapy should be administered for persistent and severe signs and symptoms.

Adolescent↗