Adipose-derived stromal vascular fraction processed with different systems for the treatment of knee osteoarthritis: a pilot study on cell proliferation and clinical results.

In recent years, the interest in stromal vascular fraction (SVF) therapy for conservative treatment of osteoarthritis has grown significantly. This study aims to assess three different processing systems (micro-fragmentation, filtration, or slow centrifugation) in terms of cell proliferation in vitro and clinical results of intraarticular injections for the treatment of knee OA. From December 2017 to June 2018, 25 procedures were performed using three different systems. A considerable improvement of the clinical condition in almost all patients already one month after the treatment with a stable effect at 6 and 12 months was recorded. Patients treated with SVF, obtained by the micro-fragmentation system, had better outcomes one month after the treatment with a mean improvement of the symptomatology higher than that found in patients treated with the filtration or slow centrifugation system. The SVF product from the same system had a higher cell proliferation capacity in vitro.

Correlation of pre-operative planning to surgical correction of opening wedge HTO: a radiographic study utilizing a manual measurement method.

High tibial osteotomy (HTO) utilizing a medial opening wedge has become a common and effective surgical technique for treatment of isolated medial compartment knee osteoarthritis secondary to varus malalignment. To reduce the risk of under- or overcorrection, accurate preoperative planning is important. This is a radiographic study to evaluate the reliability of preoperative measurement on full-length weight-bearing X-rays (FLWBXr) compared to post-operative X-rays after healing. In addition, we calculated if the intraoperative opening wedge performed was consistent with the preoperative calculation and the postoperative correction. Three independent observers measured preoperative and postoperative FLWBXr at three different times. The angle of varus deformity; the angle to correct and the wedge needed to achieve desired alignment: the angle achieved postoperatively, and the postoperative mechanical axis deviation were measured. Intra- and inter-rater reliability showed high values for all the investigated parameters. The discrepancy between the calculated wedge and the wedge actually used in surgery ranged from 1 mm of over-correction to 3 mm of undercorrection, averaging -1.3 mm. The mechanical axis crossed the tibial plateau an average of 53% ±12.7. Clustering the data by the plate type statistically significant differences were found for preoperative varus alignment, advocated correction, intraoperative correction and post-op alignment. The Dugdale method can be considered highly reliable. Possible factors affecting the final correction are: surgeon's desire not to overcorrect in young patients and minimal osteoarthritis; measurement errors; variability in the method the FLWBXr is performed. In addition, the under correction could be the result of some collapse with time or the correction could be affected by the fixation system. Further investigation should include complete post-operative evaluation of outcomes and assess the role of these potential factors and their relationship to correction. Level of Evidence: Level III, Retrospective study.

Talar exostosis (epiphyseal dysplasia): case report of posterior arthroscopic excision.

Posterior ankle impingement is a syndrome characterized by discomfort or pain at the hind foot during plantarflexion. The etiology can be divided into three main categories: overuse, trauma and anatomic abnormalities. Regarding overuse, usually patients that complain of posterior ankle pain are ballet dancers, downhill runners, field athletes and soccer players secondary to flexor hallucis tendinitis.

Comparing hybrid hyaluronic acid with PRP in end career athletes with degenerative cartilage lesions of the knee.

Cartilage lesions are very common causes of chronic knee pain in athletes. Current treatment options consist in conservative strategies, such as viscosupplementation and platelet-rich plasma injections. This randomized controlled trial aims to investigate the effect of intra-articular Hybrid Hyaluronic Acid injections compared to PRP for the treatment of cartilage lesions among athletes at the end of their career. Since March 2015, 48 professional soccer players were randomized into two groups: 24 patients received 3 injections of HHA and 23 patients received 3 intra-articular injections of PRP. All patients achieved a statistically significant clinical improvement from preoperative to postoperative time in both groups. Patients in the HHA group showed a significant superiority compared to PRP group at 3 and 6 months. Intergroup differences decrease gradually until loss of significance at 12 months follow-up. Athletes with chronic degenerative cartilage lesions of the knee responded positively both to HHA and PRP until last follow up.

Arthroscopic all-inside treatment of popliteomeniscal fascicles tears: surgical technique and results from the first 6 consecutive patients.

Athletes whose knees are subjected to sudden changes of direction and high jumps such as martial arts athletes, dancers, wrestlers and football players are at higher risk of injuring popliteomeniscal fascicles. Painful squatting and mechanical symptoms such as locking sensation are common. Current available treatments includes open or arthroscopic in repair. Arthroscopic repair with all-inside device can relieve symptoms and restore knee function. Six patients from two surgical centers with isolated popliteomeniscal fascicles tears were treated with arthroscopic all-inside repair. The surgical technique is thoroughly described. All patients showed consistent symptoms and MRI findings, as well as meniscal hypermobility during arthroscopic probing. Moreover, four out of six showed a chondral lesion of the lateral femoral condyle. All of them had their lateral meniscus sutured with one or more sutures. Symptoms were relieved and all but one were able to return to play at the pre-injury level. No postoperative complications were encountered. The diagnosis of the disruption of popliteomeniscal fascicles is challenging and often seen in athletes that play sports which involve repetitive twisting. However, patients’ complaints are consistent. Arthroscopic repair with an all-inside device showed to be a reliable and easy technique for addressing the condition, although some issues still need to be investigated, such as how much constraint the repair should provide. Arthroscopic all-inside repair of popliteomeniscal tears prove to be safe and effective in the short-term follow-up, allowing for sport activity resumption.

Sarcopenia and its relationship with osteoarthritis: risk factor or direct consequence?

PURPOSE: The aim of this review is to evaluate the clinical role of sarcopenia in patients affected by osteoarthritis (OA) of major joints. METHODS: An online database research was performed, in order to retrieve all articles investigating the relationship between sarcopenia and OA. No peer-reviewed journal was excluded. Papers in English, French, Spanish and Italian language were considered. After consulting the full-text article, five studies have been included in the review. RESULTS: Of the five studies included, four are prospective studies and only one is a cross-sectional study which retrieved data retrospectively. A total of 4,231 patients, presenting a mean age of 62.0 years, were studied. Three studies evaluated only female subjects. Weight, height and body mass index were reported in all the articles. Knee OA has been assessed using the Kellgren-Lawrence grading system and the American college of rheumatology criteria. Alterations of the lean body mass on body weight ratio have been reported to be as a significant predictive parameter in two studies. Relationship between radiographic OA and an increase in the leg lean mass has been observed in one study. CONCLUSIONS: We cannot support neither the thesis of a direct effect of sarcopenia on OA development nor the opposite relation, because the up-to-date literature lacks basic science studies concerning these topics. The absence of clinical studies regarding measurements and tools to compare sarcopenia and OA do not allow to definitely clarify this relationship.

Structural properties of a new fixation strategy in double bundle ACL reconstruction: the MiniShim.

INTRODUCTION: Double-bundle reconstruction of the ACL has become the focus of scientific and clinical interest in the last years. However, there is still a discussion about the most appropriate technique for graft fixation. Both, extracortical fixation systems like the Endobutton and aperture fixation by interference screws have advantages as well as disadvantages. Aim of this study was to analyze the biomechanical properties of a new small wedge shaped implant (MiniShim, Karl Storz, Germany) for the fixation of a soft tissue graft in double bundle ACL reconstruction and to compare it to an aperture fixation by interference screw and an extracortical fixation. METHODS: Porcine knees and flexor tendons were used for this study. 5 and 6 mm tunnels were drilled. The following fixation strategies were tested: 4 and 5 mm MiniShim (Karl Storz Germany), 6 mm interference screw (MegaFix, Karl Storz, Germany), hybridfixation by FlippTack (FlippTack, Karl Storz, Germany) and MiniShim and hybridfixation by FlippTack and 6 mm interference screw. All fixation strategies were tested with a 5 and 6 mm tendon graft. Maximum load, yield load and stiffness were recorded using a material testing machine. Load was applied in line with the bone tunnel. Grafts were cyclically preconditioned between 0 and 20 N for 10 cycles before the graft-bone-complex was loaded to failure. Statistical evaluation was performed using SPSS Version 11.0. RESULTS: Load to failure for the 5 mm graft was 81.1 and 118.0 N for the 4 and 5 mm MiniShims. Fixation by interference screw reached 237.4 N. The extracortical fixation resulted in a load to failure of 471.7 N. Load to failure for the 6 mm tendon grafts was 52.0 and 92.8 N for the 4 and 5 mm MiniShims. Fixation by interference screw resulted in a load to failure of 214.0 N. Extracortical fixation failed at 451.7 N. The difference between MiniShim and interference screw was statistically significant. Load to failure was significantly higher for extracortical fixation compared to fixation by MiniShim or interference screw. Hybrid fixation showed higher fixation strength compared to fixation by interference screw or MiniShim alone. This difference was statistically significant. Stiffness was significantly higher for fixation by interference screw compared to extracortical fixation and fixation by MiniShim. Four different modes of failure could be seen. All 4 mm MiniShims failed by slippage of the tendon past the MiniShim. In the 5 mm group the fixation failed by pullout of the MiniShim or the tendon past the MiniShim. Hybrid fixation failed by rupture of the linkage material. When the graft was fixed by an interference screw failure occurred by rupture of the tendon at the fixation side. CONCLUSION: Hybrid fixation using the MiniShim provides biomechanical properties strong enough to withstand the forces occurring during rehabilitation and comparable to the fixation strength provided by interference screw. While fixation by MiniShim alone does not provide sufficient fixation strength in double bundle ACL reconstruction, hybridfixation using a cortical fixation by FlippTack is an alternative to aperture fixation by interference screw concerning primary stability.

Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation.

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.

Successful engraftment of allogeneic PBSC after conditioning with busulfan alone.

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.

Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.

Mobilization and collection of PBSC in healthy donors: comparison between two schemes of rhG-CSF administration.

Procurement of a high number of progenitor cells is of primary interest in allogeneic PBSC transplantation. We have retrospectively compared toxicity, mobilization effect and progenitor cell yields of two different rhG-CSF schedules in 11 consecutive healthy individuals donating their PBSC. Five of them received rhG-CSF 16 micrograms/kg/d for 4 subsequent d in 2 divided subcutaneous injections (group A); similarly, 6 donors received rhG-CSF 10 micrograms/kg/d for 5 d (group B). The aphereses were started the last day of rhG-CSF treatment; 9 donors underwent 2 aphereses, one underwent 1 and another 3 procedures, always on subsequent days. Toxicity was mild, but moderate thrombocytopenia developed following apheretic collections, irrespective of rhG-CSF schedule. In all the donors WBC, as well as circulating CD34+ cells, CFU-GM, CFU-GEMM and BFU-E dramatically increased over the baseline values, peaking on d 5 or 6, with no statistical difference between the 2 groups for the height of the cell peaks. Also the peripheral lymphoid cell populations (CD3+, CD19+ and CD56+/CD3-) increased following the rhG-CSF administration. The number of MNC, CFU-GM, BFU-E, CFU-GEMM, as well as CD34+, CD3+, CD19+ and CD56+/CD3- cells collected by apheresis showed no statistical difference in the 2 groups. Overall, 8 of the 11 donors collected the target number of CD34+ cells > 4 x 10(6)/kg ideal recipient body weight with the first apheresis, with no difference between the 2 groups. Mobilization with rhG-CSF in healthy donors enables the collection of large number of progenitor cells with modest side effects. A schedule of 10 micrograms/kg for 5 d is as effective as 16 micrograms/kg for 4 d. A single apheresis would be enough in 80% of cases.

Testicular relapse of AML during chronic graft-versus-host disease induced by donor leukocyte infusion.

Treatment options for acute leukemia relapsing after allogeneic BMT include conventional chemotherapy or a second transplant; however, results are rather discouraging, the first option being associated with poor survival and the second with a high mortality rate. More recently, donor leukocyte infusion (DLI) from the original donor has been used for relapsed patients in an attempt to induce a graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with biphenotypic AML in second complete remission after relapse following allogeneic BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes, obtained after in vivo priming with rhG-CSF. The patient experienced extensive cGVHD but developed a testicular relapse while in full hematologic remission. After irradiation of the sanctuary site he remains free of disease, still with chronic GVHD, 21 months after bone marrow relapse. This case suggests that immunologically privileged sites are inaccessible to GVHD/GVL effect. This should be considered when planning salvage transplants procedures in patients at risk for extramedullary involvement.

High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.

Treatment of normal donors with rhG-CSF 16 micrograms/kg for mobilization of peripheral blood stem cells and their apheretic collection for allogeneic transplantation.

BACKGROUND: Utilization of peripheral blood stem cells (PBSC) in allogeneic transplantation requires a method for their mobilization and collection that is not inconvenient for the donor. METHODS: We administered rhG-CSF (filgrastim) 16 micrograms/kg subcutaneously for 4 days in five normal subjects (age 18-31, M = 3, F = 2), previously selected as HLA-identical donors of siblings with leukemia. All the donors gave written informed consent. On days 4 and 5 (in one donor on day 6 too), 10:l leukapheretic collection was performed with a CS-3000 (Baxter) or an AS-104 (Fresenius) cell separator through the antecubital vein. RESULTS: The WBC count reached a median peak of 57.0 x 10(9)/L on day 5. The peripheral blood CFU-GM peaked to a median level of 8908/mL on day 5 with a median increase over baseline values of 39.1 times. The CD34+ cells peaked to (median) 147.0 x 10(6)/L on day 4 with a median increase of 65.3 times. A lesser enrichment was recorded for BFU-E (median increase 12.7 times) and CFU-GEMM (median increase 15.2 times). Even CD3+ and CD56+CD3- cells increased (median 1.7 and 1.5 times, respectively). A median of 771 x 10(8) MNC (range 672-1378), 116.4 x 10(6) CFU-GM (range 47.7-145.1) and 754 x 10(6) CD34+ cells (range 477-2599) were apheretically collected. Concerning side effects, mild to moderate back pain and general minor discomfort were reported by all donors. The platelet level regularly but transiently decreased after completion of the apheretic procedures with a median nadir of 69 x 10(9)/L (range 43-126) on (median) day 7, but in no case did thrombocytopenia cause bleeding. The thrombocytopenia was more pronounced with the CS-3000 than the AS-104 apparatus. CONCLUSIONS: rhG-CSF 16 micrograms/kg x 4 days is an efficient schedule for PBSC mobilization in healthy donors, but lower doses and even a single apheresis procedure might prove similarly adequate.

Mobilization of circulating progenitor cells in multiple myeloma during VCAD therapy with or without rhG-CSF.

BACKGROUND: Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination. METHODS: Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use. RESULTS: Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly. CONCLUSIONS: The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.

Engraftment kinetics and long-term stability of hematopoiesis following autografting of peripheral blood stem cells.

BACKGROUND: We analyzed short-term and sustained hematopoietic reconstitution after high-dose therapy with peripheral blood stem cell (PBSC) support in patients with various malignant disorders. METHODS: Fifty-six patients, all with malignant hematologic disorders, were autografted between 1989 and 1994 using PBSC (47 pts) or PBSC + bone marrow (BM) cells (9 pts). PBSC were collected after mobilization with chemotherapy +/- hematopoietic growth factors (GF). RESULTS: All patients engrafted > 0.5 x 10(9)/L polymorphonuclear cells (PMN) and > 50.0 x 10(9)/L Plt at a median of 12 (8-32) and 13 (9-365) days, respectively. Thirty-nine patients were evaluable for long-term graft performance, and their hematologic values at 30 and 100 days, at 6 months and at 1, 2, 3, 4 and 5 years were retrospectively analyzed. Steady counts were recorded over the years. None of the patients had late graft failure. CONCLUSIONS: PBSC given after high-dose chemotherapy ensure a fast hematologic recovery with stable graft performance up to five years after autograft. Though this is not definitive proof of the presence of uncommitted stem cells in the PBSC population, it gives further support to the idea that PBSC are as safe as bone marrow for long-term engraftment. A delayed or incomplete recovery of platelets may occur with low PBSC counts or when disease relapse occurs rapidly after autograft.

High-dose cyclophosphamide for mobilization of circulating stem cells in chronic myeloid leukemia.

Experimental and clinical data suggest that Ph-negative myeloid progenitor cells are present, albeit suppressed, in the bone marrow of chronic myeloid leukemia (CML) patients. These residual Ph-negative cells might, in certain circumstances, regain their proliferative advantage over the leukemic Ph-positive clone. Treating CML patients with intensive chemotherapy might allow the harvest, in the early phase of recovery, of Ph-negative stem cells to be used as graft after myeloablative regimen. In our study, 6 CML patients were admitted to a program of autograft with circulating stem cells (CSC) collected after high-dose (5 or 7 g/m2) cyclophosphamide (HD-CY) mobilization. All were autografted, using busulphan 16 mg/kg and melphalan 60 mg/m2. As graft, 4 patients received CSC only, while 2 patients were also given bone marrow, as their peripheral blood CFU-GM yield was unsatisfactory. Two previously alpha-IFN-responding patients showed a slow hematologic recovery, but achieved a marked and further reduction of their Ph-positive metaphases post-graft. Moreover, in one of them, cytogenetic analyses performed on apheresis product showed a more pronounced reduction of his Ph-positive metaphases, as compared to bone marrow samples, suggesting a potential purging effect of the mobilization procedure.

High dose cyclophosphamide: stem cell mobilizing capacity in 21 patients.

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.

Monitoreo ambulatorio de la presión arterial en pacientes diabéticos: detección precoz de la hipertensión y cambios en el ritmo circadiano / Ambulatory monitoring of blood pressure in diabetic patients

El propósito de este trabajo fue establecer el comportamiento de la tensión arterial buscando hipertensión oculta y alteración del ritmo circadiano. Se estudiaron 35 pacientes diabéticos, 20 normotensos y 15 hipertensos,de los cuales 22 eran insulinodependientes y 13 no insulinodependientes, los quefueron comparados con 37 pacientes no diabéticos, 17 normotensos y 20 hipertensos.Se clasificó a los hipertensos según el criterio del Joint National Comittee de los Estados Unidos. A toda la población se le realizó monitoreo ambulatorio depresión arterial de 24 horas, aceptando como hipertensos a los pacientes que presentaban un 30 de las lecturas que excedían los valores 140/85 mm Hg. En la población diabética se evaluó el control metabólico por medio de hemoglobina glicosilada y la presencia de microangiopatía por microalbuminuria y retinofluoresceinografía. De los 35 pacientes diabéticos, 45.7 presentaron alteraciones del ritmo circadiano. Mientras que de los 20 pacientes diabéticos normotensos, al 60 sele diagnosticó hipertensión por medio del monitoreo ambulatorio.Estos resultadosponen en evidencia la necesidad de buscar hipertensión arterial en pacientes diabéticos, mediante el monitoreo ambulatorio de presión arterial de 24 horas, que permitiría el diagnóstico precoz, ofreciendo una posible prevención del daño queproduce en la evolución de las lesiones degenerativas de la diabetes y en el órgano blanco

Monitoreo ambulatorio de la presión arterial en pacientes diabéticos: detección precoz de la hipertensión y cambios en el ritmo circadiano / Ambulatory monitoring of blood pressure in diabetic patients

El propósito de este trabajo fue establecer el comportamiento de la tensión arterial buscando hipertensión oculta y alteración del ritmo circadiano. Se estudiaron 35 pacientes diabéticos, 20 normotensos y 15 hipertensos,de los cuales 22 eran insulinodependientes y 13 no insulinodependientes, los quefueron comparados con 37 pacientes no diabéticos, 17 normotensos y 20 hipertensos.Se clasificó a los hipertensos según el criterio del Joint National Comittee de los Estados Unidos. A toda la población se le realizó monitoreo ambulatorio depresión arterial de 24 horas, aceptando como hipertensos a los pacientes que presentaban un 30 de las lecturas que excedían los valores 140/85 mm Hg. En la población diabética se evaluó el control metabólico por medio de hemoglobina glicosilada y la presencia de microangiopatía por microalbuminuria y retinofluoresceinografía. De los 35 pacientes diabéticos, 45.7 presentaron alteraciones del ritmo circadiano. Mientras que de los 20 pacientes diabéticos normotensos, al 60 sele diagnosticó hipertensión por medio del monitoreo ambulatorio.Estos resultadosponen en evidencia la necesidad de buscar hipertensión arterial en pacientes diabéticos, mediante el monitoreo ambulatorio de presión arterial de 24 horas, que permitiría el diagnóstico precoz, ofreciendo una posible prevención del daño queproduce en la evolución de las lesiones degenerativas de la diabetes y en el órgano blanco (AU)