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Biomedical subjects

Yossi Cohen

Publications and source records attributed to Yossi Cohen.

At least 19 recordsLinked to original sources
PubMed2007

Development of a capitation scale for IDF career soldiers in Israel.

The Israeli National Health Insurance Law allocates a national healthcare budget to the sickness funds, which provide medical care to civilian population. Medical care for members of the IDF is financed through the budget of the Ministry of Defense and is not included in the national healthcare budget. Benefits provided to soldiers serving in the permanent forces are far more extensive than those provided to civilians. Because of no co-payments, poor management, and the cost-based budget, military healthcare costs in Israel are expected to exceed civilian healthcare costs, adjusting for age and sex. The present paper derives age- and sex-based capitation rates for military personnel, and compares military and civilian age-based expenditure and capitation rates. The study population comprised career soldiers and civilians aged 21-54 years. Expenses of career soldiers were calculated to provide information on the financial costs of medical services for each age group in 2003. Overall expenses for women were higher than for men in all age groups. As anticipated, the older the group, the higher the total expenditure for both men and women. In-patient care represented a higher percentage of the total costs for men (28.3%) than for women (22.1%). Emergency room care was higher for women in the 22-24 age group but comparable to that of men in higher age groups. Specialist visits represented a significantly higher percentage of the total costs for women than for men in the 22-24 and 25-34 age groups (by 6% and 15%, respectively). The difference decreased to 13% in the 35-44 age groups and, in the 45-54 age group, the difference for men was 14% higher than for women. Military costs were similar to civilian costs in the 22-24 age groups, higher in the following two groups, and lower in the 45-54 age group. Like in other organizations, military healthcare services might benefit from outsourcing. The inequality in medical services to soldiers and civilians, the over-use of the military healthcare system, and the decrease of standards and budgetary resources will compel the establishment of more creative means of providing these services through contracts and agreements, perhaps through the civilian sickness funds.

Adult↗
PubMed2006

A lectin array-based methodology for the analysis of protein glycosylation.

Glycosylation is the most versatile and one of the most abundant protein modifications. It has a structural role as well as diverse functional roles in many specific biological functions, including cancer development, viral and bacterial infections, and autoimmunity. The diverse roles of glycosylation in biological processes are rapidly growing areas of research, however, Glycobiology research is limited by the lack of a technology for rapid analysis of glycan composition of glycoproteins. Currently used methods for glycoanalysis are complex, typically requiring high levels of expertise and days to provide answers, and are not readily available to all researcher. We have developed a lectin array-based method, Qproteome GlycoArray kits, for rapid analysis of glycosylation profiles of glycoproteins. Glycoanalysis is performed on intact glycoproteins, requiring only 4-6 h for most analysis types. The method, demonstrated in this manuscript by several examples, is based on binding of an intact glycoprotein to the arrayed lectins, resulting in a characteristic fingerprint that is highly sensitive to changes in the protein's glycan composition. The large number of lectins, each with its specific recognition pattern, ensures high sensitivity to changes in the glycosylation pattern. A set of proprietary algorithms automatically interpret the fingerprint signals to provide a comprehensive glycan profile output.

Animals↗
PubMed2004

Umbilical cord blood transplantation--how, when and for whom?

In recent years, umbilical cord blood (UCB) has emerged as a feasible alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack HLA-matched marrow donors. Since the first case reported in 1998, more than 3500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg; however, more than 500 UCB transplantations (UCBTs) have already been performed in adults. The "naive" nature of UCB lymphocytes also permits the use of HLA-mismatched grafts at 1-2 loci without higher risk for severe graft versus host disease (GvHD) relative to bone marrow transplantation (BMT) from a full matched unrelated donor. Furthermore, UCB is rich in primitive CD16(-)CD56++ NK cells, which possess impressive proliferative and cytotoxic capacities and can be induced to expand using IL-12 or IL-15, so as to mount a substantial graft versus leukemia (GvL) effect. The main disadvantage of UCB is the low stem cell yields, resulting in higher rates of graft failure as well as delayed time to engraftment compared to BMT. One rational approach to overcome this limitation involves ex vivo expansion of UCB derived hematopoietic precursors. In this review we tried to answer the question: UCBT how, when and for whom. This procedure is mostly applicable for children and especially those with indication for full allogeneic transplantation but who lack a matched sibling donor. Experimental approaches including ex vivo expansion of CB with cocktail of hematopoietic growth factors, with or without differentiation blocking agents, co-transplantation of haploidentical and CB cells or co-transfusion of CB and mesenchymal cells may enable successful UCBT in adults and probably will result in expanding the indication to solid tumors or autoimmune disorders.

Adolescent↗
PubMed2004

Treatment of refractory autoimmune diseases with ablative immunotherapy.

Immunological manipulations are the basis of modern therapy for refractory autoimmune diseases (AID). Ablative chemotherapy with stem cell support (autotransplant) as well as targeted immunotherapy using specific monoclonal antibodies, such as rituximab and campath 1-H have become acceptable second line therapy for severe refractory AID. Until now, more than 500 autotransplants have been performed worldwide for various autoimmune disorders, including multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA) with encouraging results, although transplant related mortality (TRM) in the range between 2 and 17% still remains one of the major limitations of the procedure. Immunotherapy is a relatively safe approach associating with sustained remissions in a considerable proportion of treated patients. Better selection of patients and earlier immunotherapy, preceded an irreversible organ damage might further improve the clinical outcome of patients with AID.

Alemtuzumab↗
PubMed2004

Rapidly progressive diffuse large B-cell lymphoma with initial clinical presentation mimicking seronegative Wegener's granulomatosis.

Here we present a 40-yr-old male patient with an aggressive B-cell lymphoma, who presented 2 yr earlier with polyarthritis, and was responsive to steroids and oral methotrexate. Thereafter he developed skin and lung lesions which on biopsy consisted of mixed 'inflammatory' infiltrates with granulomatous vasculitis. A diagnosis of seronegative Wegener's granulomatosis was made and the patient received a combination of prednisone and cyclophosphamide with clinical improvement and clearance of the radiological lesions in the lungs. The patient was now completely asymptomatic for 1 yr, but then generalized lymphadenopathy appeared, which was shown by histopathology to be large B-cell lymphoma, also involving the bone marrow. Despite intensive chemotherapy, his disease could not be controlled because of primary chemoresistance, which was perhaps in some way related to exposure to the suboptimal doses of chemotherapy given during the 'inflammatory' period before the diagnosis of lymphoma was established. This case illustrates the occasional difficulty in distinguishing between extranodal lymphoproliferative diseases and autoimmune disorders especially when clonality cannot be proved. It also shows the possible risk of 'masking' a true lymphoma by treating non-malignant diseases with immunosuppressive agents, which may eventually contribute to the development of chemoresistant lymphoma.

Adult↗
PubMed2004

Cord blood biology and transplantation.

In recent years, umbilical cord blood has emerged as an alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack an human leukocyte antigen-matched marrow donor. Since 1998, about 2,500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg, however more than 500 UCB transplantations have already been performed in adults. The "naive" nature of UCB lymphocytes may explain the lower incidence and severity of graft versus host disease encountered in UCBT compared to the allogeneic transplant setting. Furthermore, UCB is rich in primitive CD16-CD56++ natural killer cells, which possess significant proliferative and cytotoxic capacities and can be expanded using interleukin-12 or 15, so as to mount a substantial graft versus leukemia effect. The major disadvantage of UCB is the low yield of stem cells, resulting in higher graft failure rates and slower time to engraftment compared to bone marrow transplantation. A rational approach thus involves ex vivo expansion of UCB-derived hematopoietic precursors.

Adjuvants, Immunologic↗
PubMed2003

Unrelated and related cord blood banking and hematopoietic graft engineering.

The first successful transplantation of umbilical-cord blood (CB) was performed in 1988 to treat a boy with Fanconi's anemia, using CB from his HLA full-matched sister. A few years later, CB transplantation (CBT) was also performed in an adult recipient, however major obstacles still prevent a wider application of CBT in this age group. The principle limiting-factor is the low numbers of nucleated (NC) and CD34+ cells available for transplantation compared to a typical bone marrow (BM)/peripheral blood (PB) allograft, resulting in a lower engraftment success as well as delayed hematopoietic recovery with its characteristic complications, including infections and transplant related mortality (TRM). Other problems include uncertainty regarding potency and efficacy of graft versus leukemia (GvL)/tumor effects in this kind of transplant, considering the reduced graft versus host disease (GvHD) manifestations and immunologic prematurity. These subjects are reviewed with orientation to technical methods directed to improve CB grafts and graft engineering.

Journal Article↗
PubMed2003

Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab.

Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.

Antibodies, Monoclonal↗
PubMed2003

Primary ALK positive anaplastic large cell lymphoma of the pancreas.

Here we present an unusual case of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALCL), appearing as a primary tumor of the pancreas which invaded into the adjacent duodenal wall, causing upper gastrointestinal bleeding. After complete resection of the tumor (Whipple's operation), the patient received 4 cycles of CHOP chemotherapy. Currently, 2 years after diagnosis the patient still remains lymphoma free. Primary ALCL of the pancreas is very rare and has only been reported on one previous occasion. Nevertheless, lymphoma should be considered in the differential diagnosis of pancreatic tumors and an attempt to obtain tissue diagnosis is always necessary before continuing with radical surgery, especially in young patients.

Adult↗
PubMed2003

Treatment of refractory autoimmune diseases with ablative immunotherapy using monoclonal antibodies and/or high dose chemotherapy with hematopoietic stem cell support.

Immunological manipulations are the basis for modern treatments of autoimmune diseases (AID). Targeted immune suppression with lymphopenic based chemotherapy, and monoclonal anti B or T lymphocytic antibodies, are integral part of the conditioning for stem cell transplantation (SCT). Immune manipulation by Cyclophosphamide (Cy), ATG, Campath and recently rituximab (RI), with or without stem cell support are the basis for emerging therapeutic modalities aiming to eradicate the autoreactive clone in various autoimmune disorders. Couple of hundreds of SCTs have been recently performed in various autoimmune disorders, mainly multiple sclerosis (MS), progressive systemic sclerosis (PSS), systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA). Preliminary results are encouraging. Better selection of patients and earlier treatment, before irreversible organ failure develops will probably improve results. Current ongoing multicenter studies are evaluating the role of SCT in MS, RA, SLE, and PSS.

Animals↗
PubMed2003

Rituximab therapy for follicular lymphoma: a comprehensive review of its efficacy as primary treatment, treatment for relapsed disease, re-treatment and maintenance.

BACKGROUND: Advances in the treatment of follicular lymphoma (FL) have been achieved through the development of newer combination regimens, mostly based upon purine analogs and/ or monoclonal antibodies, as well as recent progress in the area of stem cell transplantation. INFORMATION SOURCES: These advances have increased the need to obtain consensus regarding treatment priorities from the various options available, ranging from the traditional palliative approach through to the novel regimens available including stem cell transplantation. STATE OF THE ART: The apparent synergism between chemotherapy and rituximab, which facilitates the achievement of complete clinical (CR) and molecular remission (MR), together with the possible feasibility of maintenance and re-treatment with rituximab have increased the interest in the use of this drug as primary treatment for FL. This review summarizes the available literature and deals with the role of rituximab in refractory/relapsed FL as well as in previously untreated FL patients. The improvement in remission rates and response duration associated with immunotherapy are contrasted with the potential risks, such as the development of rituximab resistance, as well as other less recognized complications related to altered humoral immunity. PERSPECTIVES: Despite all the advances reported, treatment might still have to be individualized for patients with FL, until evidence of an important survival advantage for rituximab over chemotherapy is established. The possible role of autotransplantation for FL and the use of rituximab is also reviewed.

Adjuvants, Immunologic↗
PubMed2002

Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis.

This case report deals with an unusual leukostatic complication in a 56-year-old woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 x 10(9)/L) who presented with acute myocardial infarction (MI). After leukopheresis the patient achieved hemodynamic stabilization and rapid neurologic recovery of encephalopathy that had also developed after the infarction. Considering the central role of WBC in the remodeling of post MI myocardial tissue, it was obvious that administration of chemotherapy with its subsequent inevitable pancytopenia could impose an increased risk for further cardiac complications including myocardial rupture. Nevertheless, cytarabine-based induction chemotherapy was initiated 3 days after admission, and she achieved prolonged complete remission. Coronary angiography disclosed segmental atherosclerosis, but the only significant obstruction was in the right coronary artery. The patient died with relapsed leukemia 7 years later without recurrence of any cardiac symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing risk factor. Additional compromise to blood perfusion due to leukostasis had led to this unusual complication of AML involving a major vessel. This is the first documented case of leukostasis causing coronary artery occlusion as well as the first report of successful induction chemotherapy for AML during a myocardial infarction.

Aminoglycosides↗
PubMed2002

Large-cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine-rituximab-containing regimens: natural history- or therapy-related complication?

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This

Adult↗
PubMed2002

Development and rapid dissemination of Merkel-cell carcinomatosis following therapy with fludarabine and rituximab for relapsing follicular lymphoma.

This report deals with an unusual case of a patient with follicular small cleaved lymphocytic lymphoma who developed Merkel-cell carcinoma soon after receiving chemoimmunotherapy with a fludarabine-containing regimen and rituximab. The presentation of the Merkel-cell carcinoma in this patient was atypical because of the absence of dermal involvement and the very rapid clinical progression. In the light of recent reports which suggest a possible link between the immunocompromised state and the development of Merkel-cell carcinoma, the atypical presentation seen in this patient may indeed imply a possible link between the therapy given and the development of Merkel-cell carcinoma. To the best of our knowledge, this is the first documentation of Merkel-cell carcinoma appearing in a patient soon after treatment with fludarabine and/or rituximab.

Antibodies, Monoclonal↗
PubMed2002

Large B-cell lymphoma manifesting as an invasive cardiac mass: sustained local remission after combination of methotrexate and rituximab.

Cardiac tumor is an infrequent but serious manifestation of lymphoma and optimal management has not been well defined in these rare cases. Here we describe a patient who after autologous transplant for large B-cell lymphoma, relapsed with an invasive cardiac tumor, infiltrating the full thickness of the right myocardial wall. During therapy, she developed hemodynamic collapse due to complex atrial arrhythmias and had to be treated and stabilized in the intensive cardiac care unit. Despite initial significant regression of the cardiac tumor, new extranodal sites of lymphoma soon appeared in the skin, stomach and nervous system. Because of poor compliance, she was given salvage therapy with weekly four i.v. infusions of methotrexate and rituximab followed by monthly four maintenance cycles of rituximab alone. This produced an unexpected prolonged complete remission lasting 12 months, but she then developed a fatal leukemic phase. The relapse spared the heart and no cardiac abnormality was evident clinically or by any imaging technique. To the best of our knowledge this case, unique in terms of tumor size and extent of invasion, represents the first report of the treatment of invasive cardiac lymphoma using a combination of modest chemotherapy and rituximab.

Adult↗