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J P O'Brien

Publications and source records attributed to J P O'Brien.

At least 19 recordsLinked to original sources
PubMed2004

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

BACKGROUND: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. PATIENTS AND METHODS: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible. RESULTS: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age. CONCLUSIONS: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.

Adolescent↗
PubMed2002

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model.

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Adolescent↗
PubMed2001

The use of allograft (and avoidance of autograft) in anterior lumbar interbody fusion: a critical analysis.

The aim of this report is to analyze the validity of allograft in anterior lumbar interbody fusion. Forty-three patients underwent anterior lumbar interbody fusion using allograft in the period between 1995 and 1998. All suffered from crippling chronic low back pain with or without sciatica. Discogenic disease was verified in 40 cases by discography. All patients were investigated preoperatively with magnetic resonance imaging (MRI). The surgical technique is described. Follow-up radiographs were performed postoperatively, then at 1.5, 3, 6 and 12 months, as required. Radiological fusion was confirmed in all single-level fusions (100%, n=24). In two-level fusions the rate was 93% (n=28/30). However, radiological union could only be confirmed in 11 of the 12 levels in the three-level fusions. Allograft offers a better alternative to autograft for anterior lumbar interbody fusion. Donor site morbidity is avoided, hospital stay is shorter and fusion rates are satisfactory.

Bone Transplantation↗
PubMed2000

Granulocyte-colony stimulating factor (G-CSF) may improve disease outcome in elderly patients with diffuse large cell lymphoma (DLCL) treated with CHOP chemotherapy.

Advanced age is an adverse prognostic factor in patients with DLCL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has frequent dose-limiting toxicities, including myelosuppression. We retrospectively reviewed 50 consecutive patients > 60 years of age (median age 72) with B-cell DLCL who received CHOP with G-CSF. Patients received CHOP (median 6 cycles) at three-week intervals. G-CSF was given following all cycles of chemotherapy ("prophylactic G-CSF") in 28 of 50 patients, and following an episode of febrile neutropenia and thereafter in 19 patients, according to ASCO guidelines. Dose intensity, treatment delays, episodes of febrile neutropenia, complete response (CR) rate, disease-free survival, time-to-treatment failure, and overall survival were all analyzed according to the age-adjusted International Prognostic Index (aaIPI). The actual dose intensity for cyclophosphamide was 225.9 mg/m2/week and 0.90, respectively and for doxorubicin was 14.9 mg/m2/week (90% of ideal CHOP dosing for both drugs). Median followup was 4 years for the patients still living. Treatment delays and episodes of febrile neutropenia were less frequent among patients receiving G-CSF with all cycles of CHOP. The CR rates were 100%, 81%, 85%, and 36% for the low, low-intermediate, high-intermediate, and high aalPI risk groups, respectively. The 5-year actuarial relapse-free and overall survival for our patients were comparable to that of the cohort < or = 60 years of age and superior to the > 60 years of age cohort used to establish the aaIPI. With optimization of CHOP dosing, advanced age may not be an adverse prognostic factor for patients with DLCL. The routine use of G-CSF in elderly patients with DLCL should be further investigated.

Actuarial Analysis↗
PubMed2000

Vertebroplasty in patients with severe vertebral compression fractures: a technical report.

Vertebroplasty is a procedure in which polymethlymethacrylate (PMMA) is injected into a vertebral body compression fracture. It has been suggested that fractues greater than 65% to 70% of the original vertebral body height are too compressed to be treated successfully with this procedure. We describe six patients with severe compression fractures that were successfully treated with vertebroplasty in which the trocar was inserted in the far lateral aspect of the vertebral body, because of the typical morphology of severe compression fractures.

Aged↗
PubMed1999

Low-frequency fourier transform infrared spectroscopy of the oxygen-evolving and quinone acceptor complexes in photosystem II.

The low-frequency (<1000 cm-1) region of the IR spectrum has the potential to provide detailed structural and mechanistic insight into the photosystem II/oxygen evolving complex (PSII/OEC). A cluster of four manganese ions forms the core of the OEC and diagnostic manganese-ligand and manganese-substrate modes are expected to occur in the 200-900 cm-1 range. However, water also absorbs IR strongly in this region, which has limited previous Fourier transform infrared (FTIR) spectroscopic studies of the OEC to higher frequencies (>1000 cm-1). We have overcome the technical obstacles that have blocked FTIR access to low-frequency substrate, cofactor, and protein vibrational modes by using partially dehydrated samples, appropriate window materials, a wide-range MCT detector, a novel band-pass filter, and a closely regulated temperature control system. With this design, we studied PSII/OEC samples that were prepared by brief illumination of O2 evolving and Tris-washed preparations at 200 K or by a single saturating laser flash applied to O2 evolving and inhibited samples at 250 K. These protocols allowed us to isolate low-frequency modes that are specific to the QA-/QA and S2/S1 states. The high-frequency FTIR spectra recorded for these samples and parallel EPR experiments confirmed the states accessed by the trapping procedures we used. In the S2/S1 spectrum, we detect positive bands at 631 and 602 cm-1 and negative bands at 850, 679, 664, and 650 cm-1 that are specifically associated with these two S states. The possible origins of these IR bands are discussed. For the low-frequency QA-/QA difference spectrum, several modes can be assigned to ring stretching and bending modes from the neutral and anion radical states of the quinone acceptor. These results provide insight into the PSII/OEC and demonstrate the utility of FTIR techniques in accessing low-frequency modes in proteins.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Actinically degenerate elastic tissue is the likely antigenic basis of actinic granuloma of the skin and of temporal arteritis.

Staining technique is paramount for detecting and assessing the severe degeneration that occurs in the elastic tissues of the skin and its arteries in response to prolonged exposure to actinic radiation. With a selective "controlled" hematoxylin-and-eosin stain, actinically damaged ("elastotic") elastic tissue stains blue, as Unna described, and contrasts with normal and simply hyperplastic elastic tissue, which stains red. "Special" elastic stains such as Orcein and Verhoeff do not demonstrate this difference. When resorptive (elastolytic) giant cell reactions develop in relation to actinically degenerate elastic tissue of the skin, the papules that arise tend to form expanding, annular rings. A previously used and appropriate name for these autoimmune lesions in the skin is actinic granuloma because this name highlights the likely actinic origin and pathogenesis of many such lesions. Granulomatous inflammation in connection with actinically degenerate internal elastic lamina appears to be the basis of temporal arteritis. Actinic granulomas may occur in the skin concurrently with temporal arteritis. A recent study of temporal arteritis strongly relates its elastic tissue changes to those of "accelerated" atherosclerosis.

Adolescent↗
PubMed1999

The International Prognostic Index predicts for outcome following autologous stem cell transplantation in patients with relapsed and primary refractory intermediate-grade lymphoma.

We analyzed a group of 51 patients with primary refractory and relapsed intermediate-grade lymphoma (IGL) from the time of initiation of three cycles of second-line chemotherapy, ifosfamide, carboplatin and etoposide (ICE), in whom the intent was to administer curative high-dose chemoradiotherapy and autologous stem cell transplantation (ASCT). We sought to determine if the International Prognostic Index (IPI) assessed immediately prior to ICE, second-line IPI (sIPI), was predictive of outcome. The response rate to ICE-based chemotherapy was 69%, and 47% of the transplanted patients remain failure-free at 2.5 years. Stratification of patients based upon the sIPI demonstrated a superior 2.5 year failure-free survival (FFS) curve for patients with low (I) or low-intermediate (II) risk disease vs. those with high-intermediate (III) and high (IV) risk disease (45% vs. 9%, P<0.001). When the analysis was restricted to those patients with chemosensitive disease, the sIPI (I/II vs. III/IV) also separated patients into two distinct prognostic groups (59% vs. 20%, P = 0.04). Patients with sIPI I and II disease have a favorable outcome with ICE chemotherapy and ASCT. However, patients with sIPI III and IV disease derive limited benefit from this treatment strategy, and new approaches are needed in this patient group.

Adult↗
PubMed1998

Simultaneous combined anterior and posterior lumbar fusion with femoral cortical allograft.

The radiographic fusion rates, graft behaviour and clinical outcome of 41 patient with simultaneous combined anterior lumbar interbody fusion and posterior arthrodesis with translaminar screws were reviewed independently. In all patients a femoral cortical allograft (FCA) ring filled with autologous iliac crest cancellous bone was used anteriorly to replace the disc and achieve interbody fusion. The follow-up averaged 30.6 months, with a minimum follow-up of 24 months. All patients had disabling low-back pain with different degrees of radiating leg pain and either discogenic pain (n = 24) or a postdiscectomy syndrome (n = 15) respectively postfusion syndrome (n = 2). The overall fusion rate was 95.2% (59 of 62 segments). Time to radiographic fusion averaged 8.7 months (range 2-34 months), and in 66.1% radiographic fusion occurred without significant subsidence. In 18.6% fusion with subsidence resulted from resorption of the FCA and in 15.3% the FCA had protruded into the vertebral body. The posterior intervertebral disc height (PIVDH) increased postoperatively by 2 mm on average. However, loss of PIVDH was the rule, and occurred within the first 12 postoperative months, resulting in a negligible final gain in height of 0.3 mm on average. The segmental lordosis was increased by 3 degrees; however, loss of lordosis during the first 6 postoperative months led to a final gain in lordosis of 1.3 degrees on average. Graft incorporation occurred in 16 of 62 segments (25.8%) and was observed at an average of 21.9 months postoperatively. Subjectively, 82.4% of the patients were satisfied or highly satisfied with the clinical result of the fusion operation. In conclusion, the described technique has proven to be highly effective in achieving a high fusion rate with a good patient outcome.

Adult↗
PubMed1996

Lumbar disc disease with discogenic pain. What surgical treatment is most effective?

The diagnosis and treatment of painful degenerative disc disease remains one of the most controversial topics in the spine literature. The debate continues as to whether surgical treatment should be attempted, and if so, which surgical approach is optimal. Surgical options include the following general types of spinal fusions: posterolateral (instrumented or noninstrumented), anterior lumbar interbody, posterior lumbar interbody, and transarticular facet joint screws. Dr. Nachemson continues to take his long-standing position that the diagnosis is unreliable and that the outcomes are inadequate to justify the risks and costs. Dr. Zdeblick believes that instrumented posterolateral spinal fusions can offer a high degree of success with an acceptably low rate of complications. Finally, Dr. O'Brien believes that the pain generator is anterior and that the treatment should be anterior discectomy and interbody fusion combined with posterior transarticular facet screw fusion.

Bone Screws↗
PubMed1996

CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease.

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage-specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty-two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in four of five cases studied. All nine cases were of T- or null-cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus-positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

Adolescent↗
PubMed1996

Non-Hodgkin lymphoma: contribution of chest CT in the initial staging evaluation.

PURPOSE: To analyze incremental information derived from routinely obtained chest computed tomographic (CT) scans compared with chest radiographs in newly diagnosed non-Hodgkin lymphoma and the effect of this information on staging and therapy. MATERIALS AND METHODS: Abnormalities on chest radiographs and CT scans obtained at specific sites were prospectively identified in 181 consecutive patients with no previous treatment. When discrepant information was found, the effect on staging and treatment was determined. RESULTS: CT and chest radiographic findings were negative in 99 (55%) patients. CT findings were positive and chest radiograph findings were negative in 17 (9%). Both chest radiograph and CT findings were positive in 65 (36%) patients, 16 with identical sites of disease and 49 with more extensive intrathoracic disease at CT. Most stage changes occurred in the diffuse large cell histologic subtype. CONCLUSION: Although routine chest CT findings increased stage of disease in some patients, it had no effect on initial treatment of newly diagnosed non-Hodgkin lymphoma at this institution.

Female↗
PubMed1996

Chemosensitive epidural spinal cord disease in non-Hodgkins lymphoma.

Epidural spinal cord disease (ESCD), an infrequent complication of systemic non-Hodgkins lymphoma (NHL), can occur at diagnosis or at relapse, and is usually treated with radiotherapy, or infrequently surgical decompression. We retrospectively analyzed 140 patients with intermediate-grade NHL (IG-NHL) who were treated on a dose-intense protocol using doxorubicin, vincristine, and high-dose cyclophosphamide (NHL-15). There were seven episodes of ESCD in six (4.3%) patients. Five episodes were asymptomatic at presentation; one patient had back pain, leg numbness, and tingling; and one had radicular pain and mild leg weakness. None had malignant cells in the CSF. One patient received high-dose dexamethasone after laminectomy for diagnostic biopsy; otherwise, dexamethasone was used only as an anti-emetic prior to chemotherapy. Patients who developed ESCD at diagnosis received the planned course of NHL-15 chemotherapy as treatment for ESCD, and those treated with NHL-15 who developed ESCD at relapse were given a regimen containing ifosfamide, carboplatin, and etoposide (ICE). After chemotherapy alone, five of seven episodes showed radiographic resolution of ESCD and improvement of neurologic deficits. One patient received consolidation radiotherapy (2,700 cGy) to the spine after ICE for relapsed ESCD and had a complete response. One patient had progression of systemic lymphoma and ESCD despite chemotherapy. These data suggest that chemotherapy may be effective as initial treatment of ESCD in IG-NHL and may reduce the potential complications of spinal surgery and radiotherapy.

Adult↗
PubMed1995

Somatostatin-receptor imaging in lymphoma.

Patients with Hodgkin's or non-Hodgkin's lymphoma are staged for treatment based on the extent of known disease involvement and the histopathologic grading of the disease. Radiological techniques, including computed tomography, usually depend on estimates of lymph node enlargement and mass effects as the criterion for disease involvement. Lymphomatous tissue obtained at surgery has shown high-density somatostatin receptors. Several groups have evaluated the utility of 111In-DTPA-pentetreotide (Octreoscan, Mallinckrodt, St. Louis, MO) to detect lymphomatous tissue for more accurate staging of patients with lymphoma. The procedure is safe; both Hodgkin's and non-Hodgkins disease involvement is identified. The results, however, have not been uniformly predictive of disease involvement. Consequently, the routine use of this technique in place of currently used anatomic imaging methods is not recommended at this time. The significance of detecting somatostatin receptors in vivo in patients with malignant lymphoma requires further study.

Adult↗
PubMed1995

Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma.

PURPOSE: The reduced cardiac toxicity of the dextro-(d-) stereoisomer of verapamil (dexverapamil; Knoll Pharmaceuticals, Whippany, NJ) warrants its study as a potential multidrug-resistance (MDR) reversal agent. PATIENTS AND METHODS: Twenty-three patients with advanced renal cell carcinoma (RCC) were treated with vinblastine at a dose of 0.11 mg/kg intravenous (IV) bolus injection on days 1 and 2 every 21 days. Dexverapamil was added to subsequent cycles after resistance had been demonstrated. Dexverapamil treatment was begun 18 hours before day 1 of vinblastine administration and was given orally every 6 hours for 12 doses. Patients in group A were treated with a dose of 120 mg/m2, and those in group B were treated with 180 mg/m2 plus dexamethasone; plasma concentrations achieved in patients were correlated with in vitro effects. RESULTS: Toxicities included hypotension, asymptomatic bradycardia, and mild atrioventricular conduction delays, although one patient had dexverapamil discontinued for grade IV congestive heart failure. There were no partial or complete responses. The mean day-1 serum dexverapamil plus norverapamil plasma concentrations were 2,575 ng/mL (range, 697 to 6,015 ng/mL) for group A and 1,654 ng/mL (range, 710 to 4,132 ng/mL) for group B at the time of vinblastine administration. These concentrations were in the range of those that reversed vinblastine resistance in vitro. CONCLUSION: The advantage of dexverapamil as an MDR reversal agent is its potential for achieving desired blood levels with substantially less toxicity than the racemic mixture of verapamil. Based on tolerability, it is a suitable drug for further study in clinical trials of malignancies other than RCC that attempt to achieve MDR reversal. The dose of 120 mg/m2 given orally every 6 hours, with dose escalation based on individual tolerance, represents a feasible schedule to be considered for such studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗