Predictor factors for renal outcome in renal artery stenosis.

BACKGROUND: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure. Correction of renal artery stenosis (RAS) may fail to stabilize or improve renal function. AIMS OF THE STUDY: Carotid and aortic Intima media thickness (IMT), resistance renal resistance index (RI), arterial blood pressure (BP), serum creatinine (SCr), creatinine clearance (CrCl), proteinuria and uricemia were considered as possible predictive factors and measured before renal-artery stenosis correction and during 12 months follow-up. MATERIALS AND METHODS: we performed an observational study on a total of 55 patients to find predictive factors of the outcome of renal function after renal percutaneous transluminal angioplasty and stenting (RPTAs). RESULTS: We found that uricemia, proteinuria and IR were higher at baseline in patients who worsened renal function after revascularization. CONCLUSIONS: The identification of predictive factors (uricemia; proteinuria and RI) of chronic kidney disease (CKD) progression in patients with RAS undergone revascularization could be useful to predict renal long term outcome and to select patients that really could benefit of this.

[The support of the ultrasonography of the shoulder in the diagnosis of polymyalgia rheumatica with normal erythrocyte sedimentation rate]. / L'ausilio dell'ecografia della spalla nella diagnosi della polimialgia reumatica con velocità di eritrosedimentazione normale.

Polymyalgia rheumatica (PMR) is a chronic inflammatory syndrome that affects the elderly population and whose diagnosis is mainly based on clinical criteria taking little advantage of the latest innovatory methods of diagnostic imaging, for instance ultrasonography. Although it is generally characterised by increasing of inflammation values as well as pain and stiffness on the shoulder and pelvic girdles, there is a significant percentage of patients with PMR whose erythrocyte sedimentation rate (ESR) is normal; in this case to make a diagnosis is difficult. The purpose of our study is to demonstrate how useful ultrasound investigations on the shoulders joints could be in order to make a diagnosis of PMR, especially for those patients with atypical normal ESR. Our case control study included 23 patients with atypical PMR and 88 patients with standard symptomatic PMR; both groups underwent shoulder ultrasound scans before receiving steroid therapy. As it has been previously shown, the ultrasound method is able to detect distinctive aspects in the joints and tissues of the patients with PMR; so that we could find that 90% of the patients with PMR of both groups suffered from bilateral subdeltoid bursitis. This disorder is seldom found in healthy people and consequently its presence could be considered a useful diagnostic test/check for/of PMR independently from ESR values.

CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma.

Thirty untreated patients, median age 69 years (range 60 - 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.

Indications and results of endovenous laser tratment (EVLT) for greater saphenous vein incompetentce. Our experience.

AIM: Endovenous laser treatment (EVLT) seems to be a safe and less invasive method for the treatment of the great saphenous vein (GSV) incompetence. The aim of our study was to evaluate the indications and results of EVLT. METHODS: Between January 2003 and October 2004, 77 patients (55 C3 and 22 C4) underwent EVLT. In 23 cases phlebectomy was performed, in 16 patients a subfascial perforator vein ligations occurred. In 62 patients we used a percutaneous access to the distal GSV, in 15 cases a surgical isolation was performed. In all cases a 600 nm with 1 mm diameter laser was used. RESULTS: Follow-up was performed for a period of 6 months and showed GSV recanalization in 2 cases; 18 patients (23.3%) developed a transient postoperative pain along GSV, in 4 (5.1%) of them the pain persisted for 3 months. In 6 cases a reversible paresthesia due to a lesion of the saphenous nerve were recorded (7.7%) and in 1 case (1.2%) a skin burn occurred. No deep vein thromboses were observed. CONCLUSIONS: EVLT is a safe technique, with low incidence of recanalizations and postoperative complications. Our opinion is to extend the indication in selected cases of GSV incompetence.

Management of acute lower limb ischemia following percutaneous arterial closure device application: our experience.

INTRODUCTION: The Authors report their experience in the management of acute lower limb ischemia following percutaneous arterial closure device application. PATIENT AND METHODS: Five patients required an emergency vascular operations for acute lower limb ischemia. The symptoms onset was < 1 hour in 1 case, 4-12 hours in 2 cases and > 24-36 hours in 2 cases. A preoperative angiography was performed in all the cases. A transfemoral embolectomy was carried out. Direct suture repair were performed in three cases, vein patch angioplasty was carried out in two cases. In one case, a common femoral artery endarterectomy was performed. RESULTS: No post-operative mortality and limb loss occurred. CONCLUSIONS: Acute lower limb ischemia due to closure devices required an extensive approach with reconstruction in high risk septic area. Angiography is mandatory for surgical strategies. We prefer direct suture repair and vein path angioplasty for vascular reconstruction.

Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients.

PURPOSE: Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma. PATIENTS AND METHODS: From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient). RESULTS: Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported. CONCLUSION: Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites.

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.

Minimal residual disease status in transplanted chronic myelogenous leukemia patients: low incidence of polymerase chain reaction positive cases among 48 long disease-free subjects who received unmanipulated allogeneic bone marrow transplants.

Forty-eight long-term disease-free chronic myelogenous leukemia (CML) patients, who had received unmanipulated allogeneic bone marrow transplants (BMT) for eradication of the Philadelphia (Ph1)-positive clone were studied by polymerase chain reaction (PCR), using a very sensitive PCR procedure and very stringent criteria for preventing and revealing contamination. Nine patients (18%) were positive at the first PCR examination, but only one patient remained PCR positive four years after. However, a second PCR analysis performed on new bone marrow samples obtained at a median interval of 14 months (range 6-16) after the first specimen collection from six of nine originally positive cases, and from 16 of 39 originally negative cases, showed that only one of the six positive cases remained positive, whereas negativity was confirmed in all the originally negative patients. These data are evidence that the Ph1-positive clone is apparently completely eradicated in the majority of CML patients who survive disease-free long-term after an unmanipulated allogeneic BMT and that only sporadic cases remain PCR-positive four years post-BMT. The data also show that at least two sequential bone marrow samples for each patient must be analyzed before drawing conclusions regarding the stable persistence of BCR/ABL transcripts and the minimal residual disease status.

Vascular Thoracic Outlet Syndrome staging and treatment.

Thoracic Outlet Syndrome (TOS) is a well known lesion. Sophisticated imaging techniques can clearly highlight any anatomical damage and a wide range of therapeutic choices are available. It would seem obvious that any given patient should obtain the same treatment irrespective of the medical institution he contacts, but this is not the case. Instead each specialist may recommend different treatments: physiatrist, neurologist, surgeons (thoracic, vascular, neuro, orthopedic). Everyone preserves his specific language and there is no univocal treatment plan consensus for this complex syndrome. Evidently, the correct staging of TOS is still an unresolved question. In order to solve this problem, we collected all clinical and instrumental aspects of the syndrome into a clear, precise classification. Similar to TNM staging of malignant diseases, we used a grouping model based on the three mainly involved anatomical structures: N (= Nerves; brachial plexus and sympathetic fibers), A (= Artery; subclavian-axillary), V (= Vein; subclavian-axillary). We named it the NAV staging of TOS. A retrospective examination of our case records confirmed a valid and useful correlation between the proposed NAV staging and the therapeutic procedures that were actually applied. It is now essential to perform a multi-centre study to extend the validity of our staging.

Rupture of an isolated true superficial femoral artery aneurysm: case report.

True isolated atherosclerotic aneurysm of the superficial femoral artery is a rare pathology. We report a case of ruptured superficial femoral artery aneurysms (SFAA) not associated with aortic, common femoral or popliteal artery aneurysms. An emergency surgical procedure was performed and, after endoaneurysmal branches ligation, a ePTFE graft interposition was performed. The literature review shows a prevalence of rupture as compared with ischemic complications and the need for surgical repair in case of SFAA with diameter twice the normal vessel size. Early diagnosis and management are recommended because of the lower morbility and mortality rates associated with elective surgery by comparison with emergency procedures.

Low dose arabinosyl cytosine for treatment of myelodysplastic syndromes and subacute myeloid leukemia.

Several agents, including arabinosyl cytosine (ARA-C) at a low concentration, can induce leukemic myeloblasts to mature to a variable extent. The therapeutic implications of this observation are worth investigating. A few case-reports have shown that low dose ARA-C can be useful for treatment of the myelodysplastic syndromes (MDS) and of acute myeloid leukemia (AML). However, no information is available yet on the proportion of patients who can be expected to respond. We treated by low dose ARA-C (20-30 mg/sqm/day i.v. or i.m. for 7-10 days) 20 consecutive patients. A complete remission of 5 months was obtained in one of nine cases of subacute myeloid leukemia (SAML). A partial remission (complete normalization of blood counts with a slight excess of marrow blast cells) was obtained twice in one of 11 cases of MDS. An increase of Hb level (more than 11.5 g/dl) was obtained and maintained for 12 months in a case of MDS. A short-lasting increase of granulocyte count was obtained in another two cases of MDS and SAML respectively. It is suggested that low dose ARA-C can advantageously modify the proliferation to maturation imbalance of leukemic cells by slowing down cell proliferation rate. However, the proportion of patients who respond is probably low. This treatment is at a very early experimental stage and should be probably limited to selected cases of MDS and subacute or acute myeloid leukemia.

Cytogenetic events after bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia.

Allogeneic bone marrow transplantation is the only way to cure patients with Ph1+ chronic myeloid leukemia. It is commonly assumed that, in order to obtain a cure for the patients, the leukemic clone must be completely destroyed by the conditioning treatment and the donor's bone marrow must repopulate the hemopoietic niches leading to a "complete chimera". However, cytogenetic analyses, supported by molecular ones, indicate that Ph1+ cells, far from being completely destroyed by chemo-radiotherapy may persist for a long time, probably in the majority of the patients. As demonstrated by the outcome of patients receiving T-cell depleted marrow, immune mechanisms must be involved in controlling and progressively reducing the size of the residual leukemic clone. Furthermore, immunodulating therapeutic strategies, represented by cyclosporin-A discontinuation or alpha interferon treatment, may successfully reduce the Ph1+ cell population even after a full relapse.

bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia: higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase.

The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT.

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.

Host origin of bone marrow fibroblasts following allogeneic bone marrow transplantation for chronic myeloid leukemia.

We investigated the origin of the fibroblastic compartment of stromal hematopoietic microenvironment in eight chronic myeloid leukemia (CML) patients following allogeneic BMT. At the time of the study, all eight CML patients showed complete and long-lasting (14-87 months) engraftment of donor hematopoiesis and absence of clonal Ph-positive hematopoiesis. The study was carried out using in vitro amplification of informative DNA sequences: a Y chromosome specific DNA fragment in three patients who received a sex-mismatched allograft, and locus D1S80, a variable number of tandem repeats polymorphism, in five patients who received a sex-matched allograft. In all cases bone marrow fibroblasts were of recipient origin. These data indicate that with current BMT procedures the stromal compartment of hematopoiesis is not transplantable in humans.

Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.

One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.

Detection of occasional and clonal chromosome aberrations in patients with acute non-lymphocytic leukemia after autologous bone marrow transplantation.

Clonal chromosome aberrations observed in patients who have relapsed after autologous bone marrow transplantation (ABMT) are usually related to the cytogenetic abnormalities observed at diagnosis. In order to assess this relationship, we evaluated 30 acute non-lymphocytic leukemia (ANLL) patients who underwent ABMT at out institution and had evaluable serial cytogenetic studies before and after ABMT. Seventeen patients (57%) showed no chromosome aberrations after ABMT in any of the studies performed, while 13 patients (43%) carried abnormalities. In eight out of 30 patients (27%0 the abnormal karyotype after ABMT was associated with hematologic relapse. The cytogenetic abnormalities were: (1) the same as at diagnosis without additional abnormalities in five patients; (2) the same as at diagnosis but with additional abnormalities in three patients. In one patient a different karyotype from that of diagnosis was detected and a myelodysplastic syndrome was clinically evaluable. Furthermore, occasional and single cell chromosome abnormalities were observed in four patients (13%), none of whom relapsed. The new and additional clonal cytogenetic abnormalities observed after ABMT were found in eight patients (27%), suggesting that this event may not be so frequent, that is presumably associated regimen. The re-appearance of the chromosome aberrations after ABMT and the relationship with the risk of relapse are discussed.

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells.

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.

Evaluation of complete remission in hairy cell leukemia patients treated with alpha-IFN.

In 10 HCL patients, who following treatment for more than 1 year with alpha-IFN, had achieved a normalization of the splenomegaly and a disappearance of circulating hairy cells together with a complete restoration of all peripheral hematological values, a multiple assessment of the apparent complete remission (CR) was carried out. The presence of residual disease was investigated by bone marrow histology, bone marrow immunohistochemistry, immunoglobulin (Ig) gene analysis and on the basis of the serum levels of the soluble form of the Interleukin-2 receptor (sIL-2R). Examination of bone marrow biopsies showed a pattern of CR in 5 cases; 4 of them revealed no evidence of Ig heavy chain gene rearrangement, as well as a near normalization of the serum levels of sIL-2R. Immunohistochemical studies were carried out on embedded paraffin sections with the monoclonal antibody 4KB5 (CD45R) and were assessable in 4 of the 5 patients considered in CR and in 3 of the 4 cases with no Ig gene rearrangement. In 2 the pattern of CR was confirmed, while in the 3rd a minimal but persistent disease (5%) was suspected.