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Biomedical subjects

R E Marcus

Publications and source records attributed to R E Marcus.

At least 55 records · Page 3Linked to original sources

Triple arthrodesis for diabetic peritalar neuroarthropathy.

From 1963 to 1990, the senior authors (R.E.M. and K.G.H.) performed eight triple arthrodeses in seven patients with diabetes mellitus with sensory loss in the lower extremities. By clinical and roentgenographic examination, all patients were diagnosed with peritalar neuroarthropathy before surgery. All patients underwent a two-incision triple arthrodesis with internal fixation. Patient follow-up averaged 44 months and included repeat physical examinations and radiographs. All patients went on to clinical union and were satisfied with the procedure. One patient had prolonged wound drainage that resolved with antibiotic therapy; another had a residual rocker-bottom deformity and plantar ulceration that resolved after modification of custom shoe wear. We believe comprehensive management of diabetic peritalar neuroarthropathy can include surgical arthrodesis of the involved joints. The disease process and surgical indications are discussed.

Adult↗

Autologous bone marrow transplantation for second or greater complete remission of acute myeloid leukaemia and acute lymphoblastic leukaemia.

Twenty patients with acute leukaemia in second or greater complete remission have undergone autologous bone marrow transplantation (ABMT) in our centre. Twelve patients had acute myeloid leukaemia (AML) and eight patients had acute lymphoblastic leukaemia (ALL). Six of the patients treated for AML remain in CR. Of the eight patients with ALL, all have died within one year of transplantation. In the patients with AML there was no relationship between the duration of previous CR and outcome of ABMT.

Acute Disease↗

Peripheral blood progenitor cell harvesting in multiple myeloma and malignant lymphoma.

Peripheral blood progenitor cells are being used increasingly as part of the treatment protocol for a variety of haematological malignancies. The most appropriate mobilisation therapy and the optimum collection procedures have yet to be fully elucidated. 28 patients with myeloma (9), NHL (11) and HD (8) underwent PBSC mobilisation and harvesting between November 1992 and October 1993. Two protocols were used; the myeloma group received high-dose cyclophosphamide, 7 g/m2 + G-CSF and were leucapheresed on 5 consecutive days during the recovery period using the Haemonetics V50 and the lymphoma group a lower dose of cyclophosphamide, 3 g/m2 + G-CSF followed by leucapheresis on 2 or 3 occasions using a Cobe Spectra. Median time to achieve a WBC of 1 x 10(9)/l during the recovery phase, was 14 days (11-16) and 10 days (9-15) respectively. Median numbers of MNC and CFU-GM collected for the myeloma group were 5.9 x 10(8)/kg (2.5-13.5) and 69.4 x 10(4)/kg (9.9-268.1) and for the lymphoma group. 5.1 x 10(8)/kg (1.2-11.1) and 35.4 x 10(4)/kg (1.2-129.7). Three patients with lymphoma had a low yield of CFU-GM, two of which did not proceed to autograft. The third patient failed to engraft and died despite receiving bone marrow backup. For the remaining 25 patients, median time to neuts > 0.5 x 10(9)/l and platelets > 50 x 10(9)/l was 9 (8-13) and 11 (9-23) days for the myeloma group and 12 (9-15) and 13 (9-180) days for the lymphomas. We found a strong correlation between CD34+ cells and CFU-GM from the last 9 patients. There is a correlation between CFU-GM infused and speed of engraftment. All patients who received > 10 x 10(4) CFU-GM/kg showed a rapid engraftment for neutrophils and platelets. In all cases, when > 4 x 10(8)/kg MNC were harvested, > 10 x 10(4) CFU-GM/kg were obtained. Sufficient cells for a rapid engraftment can be obtained from 2 leucaphereses in the majority of patients. The recovering peripheral blood WBC provides a good indicator of when to harvest. The target value of CFU-GM can be predicted by the number of cells harvested and by the number of CD34 positive cells in the leucapheresis product.

Aged↗

The difficult diagnosis of posterior tibialis tendon rupture in sports injuries.

Posterior tibialis tendon rupture is a diagnosis that is often missed in sports-related injuries. This is thought to be secondary to the nonspecific clinical findings in healthy, active individuals, and the lack of any laboratory or radiographic test to reliably confirm the diagnosis. We report five cases of surgically confirmed posterior tibialis tendon rupture secondary to sports-related trauma. Based on our review of these patients, the diagnosis of posterior tibialis tendon rupture should be strongly suspected in the adult patient presenting with a history of a twisting ankle injury, especially in the setting of high-impact loading and generalized medial ankle pain and swelling. A flexible asymmetric pes planus and forefoot pronation deformity with absence of posterior tibialis tendon function on manual testing is seen on examination. The patient is usually unable to perform ipsilateral single leg heel rise and has less severe pes planus of the contralateral foot. This study reviews the presentation, pathophysiology, diagnosis, and treatment of posterior tibialis tendon rupture.

Adult↗

The relationship between hematocrit, blood lost, and blood transfused in total knee replacement. Implications for postoperative blood salvage and reinfusion.

The relationship between patient hematocrit level, red blood cell volume lost, and blood units transfused is important in determining conservation strategies in patients undergoing total knee replacement surgery. In a series of 30 such patients, 3 (10%) received allogeneic blood, despite preoperative autologous blood donation in 28 patients. There was no evidence that the degree of anemia affected rate or volume of postoperative wound blood drainage. The wound drainage volume that could have been salvaged and reinfused in bilateral procedures was substantial. A combination of one or more conservation techniques along with conservative transfusion practice is necessary to achieve minimal allogeneic blood exposure.

Aged↗

Peripheral blood stem cell transplantation after high-dose therapy in patients with malignant lymphoma: a retrospective comparison with autologous bone marrow transplantation.

We report the results of peripheral blood progenitor cell (PBPC) harvesting in 22 patients with lymphoma who underwent leucapheresis after cells were mobilised using 3 g/m2 cyclophosphamide and G-CSF. In 19 patients, the total CFU-GM collected was greater than 7.5 x 10(4)/kg. These patients underwent successful autologous PBPC transplantation. This group of patients was compared to a historical group of 24 patients with lymphoma who underwent ABMT with the same conditioning chemotherapy. The time to engraftment of neutrophils to 0.5 x 10(9)/l was significantly reduced (median 11 days vs 19 days, P < 0.0001) and consequently in-patient stay was reduced (median 21 days vs 28 days, P < 0.001). Blood product support (median 3 vs 4 units blood, P = 0.02; median 15 vs 40 units platelets, P = 0.005) and use of TPN (median 0 days vs 8 days, P < 0.001) were reduced. We estimate a saving of approximately pounds 2370 per patient using PBPC for autologous transplantation compared to bone marrow progenitor cells. This saving is significant (P < 0.001).

Adult↗

Autografting for multiple myeloma: a 5-year experience at a single institution.

Over a 5-year period, we have performed 33 autologous bone marrow or PBPC transplantations for multiple myeloma. Nine patients were in complete remission and 24 in partial remission at time of transplantation. Conditioning regimens were BEM (BCNU, etoposide and melphalan) in 29, busulphan and cyclophosphamide in three and melphalan alone in one. Two patients (6%), died within 3 months of transplant-related mortality, seven (21.3%), died of disease progression at a median follow-up of 11 months (range 4-24). Twenty-four patients (72.7%) are alive at a median follow-up of 15 months (range 4-61). Of nine patients transplanted in CR, four have relapsed and are alive and five remain in CR. Of 24 patients transplanted in PR, nine have died, six remain in PR, eight achieved CR and one has progressive disease. The overall median progression-free survival (PFS) is 31 months (95% CI = 20-42). For patients transplanted in PR the median PFS is 24 months (95% CI = 22-26), the median PFS for patients transplanted in CR has not yet been reached. The median PFS for patients achieving CR pre- or post-transplantation was better than for patients neither achieving CR pre- nor post-transplantation (P = 0.05). The median PFS was also significantly improved for patients requiring only primary therapy, compared to patients needing second-line therapy to achieve CR or stable PR prior to transplantation (31 vs 11 months, P = 0.02).

Adult↗

Molecular detection of clonally rearranged cells in peripheral blood progenitor cell harvests from multiple myeloma patients.

Peripheral blood progenitor cells (PBPC) are increasingly used for autologous reconstitution following high-dose chemotherapy in multiple myeloma but it is unclear whether these cells are less likely to be contaminated with malignant cells than bone marrow (BM). We have investigated this using immunoglobulin heavy-chain (IgH) gene fingerprinting, a polymerase chain reaction based technique with a sensitivity of 0.1-0.01% (10(-3)-10(-4)). We have looked for patient-specific IgH rearrangements in leukapheresis samples from eight myeloma patients undergoing PBPC harvest. Seven were in first remission (six partial, one complete) and one in second complete remission. Mobilization of PBPC was accomplished using cyclophosphamide (4 or 7 mg/m2) and rhG- or GM-CSF. Between two and five leukaphereses were performed in each patient. Patient-specific IgH rearrangements were identified in diagnostic BM in all patients and bands of identical size were found in one or more leukaphereses from 6/8 patients. Overall, 14/32 leukaphereses were shown to be contaminated. Two patients who showed contamination of at least one PBPC harvest had BM harvests in which contaminating cells were not detectable, suggesting that PBPC are not necessarily less likely to be contaminated than marrow stem cells. These results indicate that PBPC harvests from the majority of myeloma patients are likely to contain contaminating cells. Further studies are needed to determine whether these cells are clonogenic and whether they contribute to relapse.

DNA Fingerprinting↗

Two unusual neurological presentations of granulocytic sarcoma in Philadelphia positive chronic myeloid leukaemia.

Granulocytic sarcoma (GS) is a rare extramedullary tumour consisting of immature myeloid precursors. It occurs most commonly in association with myeloid leukaemias and myeloproliferative disorders. Rarely there may be no evidence of haematological malignancy. We describe neurological presentations of GS in two patients with Philadelphia (Ph) positive chronic myeloid leukaemia (CML). In both cases the bone marrow was in chronic phase at the time of presentation of the GS, but there was rapid subsequent transformation into the blastic phase.

Adult↗

Autologous bone marrow transplantation for Hodgkin's disease--a five-year single centre experience.

The results from 40 patients who have undergone autologous bone marrow transplantation (ABMT) for relapsed or refractory Hodgkin's disease between March 1988 and September 1992 have been analysed. In contrast to our results in patients with relapsed HD, our results in patients with refractory HD are comparatively poor. Conventional salvage chemotherapy also seems inappropriate in these patients and we therefore believe they should be offered high-dose chemotherapy before their disease becomes refractory to conventionally scheduled regimens. Peripheral blood stem cell (PBSC) transplant now offers an attractive alternative to ABMT and may replace both intensive salvage chemotherapy and ABMT as the optimum treatment for patients who fail to respond to conventional chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of recombinant human erythropoietin therapy on red cell expansion during autologous blood donation.

As the result of the institution of coordinated programs involving regional blood centers, hospital blood banks, information services, and physicians, preoperative autologous blood donation, a previously underutilized practice, has become a standard of care in a number of elective surgical procedures. In addition, the administration of recombinant human erythropoietin has been shown to facilitate the collection of autologous blood from patients scheduled for elective orthopaedic surgery. An analysis of the findings in a study of 263 orthopaedic surgical patients in which the relationship between autologous blood ordering, collection and storage, and subsequent blood transfusion was studied indicates that both blood ordering and blood procurement practices are significant factors with regard to allogeneic blood exposure.

Blood Donors↗

Liquid storage of peripheral blood progenitor cells for transplantation.

Peripheral blood progenitor cells (PBPC) were mobilised by recombinant human G-CSF (rhG-CSF) and cyclophosphamide, harvested by apheresis from 9 patients with NHL and stored at 4 degrees C without further manipulation. They were then reinfused after high-dose chemotherapy. We monitored the change in colony-forming units-granulocyte, macrophage (CFU-GM) proliferation as well as plasma glucose, lactate and pH levels over the period of the study. In an attempt to maintain CFU-GM numbers, rhG-CSF was added to storage bags at collection and 48 h later. Our observations suggest that cell viability is well maintained and that CFU-GM numbers rise over the first 48 h of storage before falling rapidly. Metabolic changes cause a fall in the pH and glucose levels with a reciprocal rise in plasma lactate. The addition of rhG-CSF at a concentration of 10 ng/ml to cells in storage showed no detectable benefit. Following storage for 96 h, 77% (SEM +/- 8%) of the initial CFU-GM remained.

Blood Component Removal↗

Technetium (99mTc)-labelled white cell scanning, 51Cr-EDTA and 14C-mannitol-labelled intestinal permeability studies: non-invasive methods of diagnosing acute intestinal graft-versus-host disease.

We describe a case of a 38-year-old female who presented with diarrhoea and abdominal pain 27 days after a second 'top-up' allogeneic marrow infusion for acute myeloid leukaemia (AML) in first remission. A clinical diagnosis of gut graft-versus-host disease (GVHD) was made. Technetium (99mTc)-labelled white cell scanning and intestinal permeability studies using 51Cr-EDTA and 14C-mannitol were undertaken to confirm the diagnosis. The 99mTc white cell scan showed extensive uptake in the small bowel and the urinary excretion of 51Cr-EDTA was increased, the results being consistent with intestinal inflammation and gut GVHD. 99mTc white cell scanning and intestinal permeability studies may assist in the diagnosis of gut GVHD and in assessing its extent and response to treatment.

Acute Disease↗

The effect of patient size and dose of recombinant human erythropoietin therapy on red blood cell volume expansion in autologous blood donors for elective orthopedic operation.

BACKGROUND: Recombinant human erythropoietin (EPO) therapy has been known to enhance erythropoiesis and facilitate autologous blood donation before elective orthopedic operations. However, the optimal EPO dose in this setting remains undefined. To help determine this, we have examined the effect of patient weight and EPO dose on red blood cell (RBC) volume expansion. STUDY DESIGN: Forty-six nonanemic autologous blood donors enrolled at our institution in two previously reported multicenter clinical trials were analyzed. Patients received either placebo or EPO (150, 300, or 600 units [U] per kg) given intravenously at each of six AB blood type donation visits. RESULTS: Total preoperative RBC volume expansion over a 22 day period was 465 +/- 135 mL (mean +/- SD) in patients receiving a placebo and 588 +/- 201 mL, 735 +/- 144 mL, and 881 +/- 292 mL in patients receiving graded concentrations of EPO. When RBC volume increase was corrected for patient weight and EPO dose, patients receiving placebo or EPO (150, 300, and 600 U per kg) expanded RBC volume by 5.9 mL per kg in patients receiving placebo and 7.9, 9.1, and 10.9 mL per kg in patients receiving EPO, respectively (p < 0.02 for each EPO group compared with placebo group). A direct relationship between EPO dose and RBC volume increase (response) over 22 days was determined by the linear regression equation: RBC volume (mL per kg) = 6.34 + 0.0013X, r = 0.98, where X equals total units EPO administered (per kg body weight). CONCLUSIONS: We conclude that EPO dose can be based on anticipated blood losses and transfusion needs in autologous blood donors before orthopedic operation.

Aged↗

C-MYC translocations in de novo B-cell lineage acute leukemias with t(14;18)(cell lines Karpas 231 and 353).

Rare de novo acute leukemias of mature B cells may exhibit the chromosomal translocation t(14;18)(q32.3; q21.3). We report the preliminary characterization of two cases that exhibited not only t(14;18)(q32.3;q21.3) but also the novel translocation t(8;9)(q24.1;p13.3), involving the C-MYC locus with unknown sequences at 9p13.3. From these cases, two Epstein-Barr virus negative cell lines (Karpas 231 and 353) with features identical to those seen in fresh cells from the patient have been derived. Both cell lines have complex karyotypes: in addition to both t(14;18)(q32.3;q21.3) and t(8;9)(q24.1;p13.3), cell line Karpas 231 exhibited three-way translocation t(1;3;11) (q42.3;q27.1;q23.1), whereas Karpas 353 exhibited t(1;3;7)(p32.1;q21.1;q22.1). Both cases retained immunophenotypes characteristic of mature B cells with no evidence for commitment to other hematopoietic lineages. Both cases expressed abundant, normal-sized C-MYC transcript, but no rearrangement of C-MYC DNA sequences could be detected using probes that span 80 kb around the C-MYC coding sequences. Breakpoints within the BCL-2 gene were divergent. In Karpas 353 the BCL-2 breakpoint occurred within the 3' untranslated major breakpoint region (mbr) of the gene, whereas, in Karpas 231, breaks in both the 3' mbr and in the region 5' of the gene were detected. The cytogenetic combination of t(14;18)(q32.3;q21.3) and t(8;9)(q24.1;p13.3) has been previously reported in diffuse B cell lymphomas. This combination may be a new recurrent abnormality, of central pathogenic importance in the transformation of B cells to high grade malignancies through simultaneous deregulation of BCL-2 and C-MYC genes, constitutive expression of C-MYC being driven by currently unknown DNA sequences on chromosome 9p13.3. The presence of other complex translocations including those affecting 11q23.1 may further accelerate the process of acute transformation.

Acute Disease↗