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Biomedical subjects

L Volin

Publications and source records attributed to L Volin.

At least 73 records · Page 4Linked to original sources

Cytomegalovirus is frequently isolated in bronchoalveolar lavage fluid of bone marrow transplant recipients without pneumonia.

We prospectively studied the presence of cytomegalovirus in bronchoalveolar lavage through virus isolation in 21 bone marrow transplant recipients before and after transplantation. All 14 lavage specimens collected before bone marrow transplantation were negative for cytomegalovirus. During the period from 20 to 90 days after transplantation, 12 of 24 lavage specimens (50%) from 14 patients without lung problems were positive for cytomegalovirus. Cytomegalovirus was isolated from 4 of 10 lavage specimens (40%) in 7 patients with pneumonia during the same interval. We conclude that culture for cytomegalovirus in bronchoalveolar lavage fluid is not a reliable method for establishing the virus's causative role in pneumonia soon after bone marrow transplantation. Among 14 patients in whom bronchoalveolar lavage was done at an asymptomatic stage, 6 of 9 patients with cytomegalovirus and none of 5 without cytomegalovirus in the lavage fluid later developed pneumonia. All of the patients subsequently developing pneumonia also had acute graft-versus-host disease, suggesting an immunopathologic mechanism, possibly triggered by cytomegalovirus, for cytomegalovirus-associated pneumonia.

Adult↗

Cardiac involvement in bone marrow transplantation: serial changes in left ventricular size, mass and performance.

Forty-five consecutive adult patients with haematological malignancies were studied prospectively to evaluate cardiac involvement in bone marrow transplantation (BMT). Echocardiography and measurement of systolic time intervals were performed before conditioning with cyclophosphamide (CY) (120 mg kg-1) and total body irradiation (10-12 Gy), and repeated 1 month and 1 year after BMT. The left ventricular (LV) changes at the 1-month study included increases in mass index (85.1 +/- 4.0 g m-2 vs: 76.1 +/- 3.3 g m-2, mean +/- SE; P less than 0.001) and in the pre-ejection period/ejection time ratio (0.46 +/- 0.01 vs. 0.36 +/- 0.01, P less than 0.001), and decreases in fractional shortening (24.9 +/- 1.0% vs. 27.9 +/- 0.8%, P less than 0.01) and in the peak normalized diameter lengthening rate (2.2 +/- 0.1 s-1 vs. 2.6 +/- 0.1 s-1, P less than 0.01). Four patients developed congestive heart failure. Twenty-four patients were alive and relapse-free 1 year after BMT. The LV measurements were then no longer different from the pre-transplant readings. Thus BMT that is preceded by conditioning with CY and total body irradiation results in increased LV mass and impaired systolic and diastolic LV function. These changes are mostly subclinical, and are also reversible if the recipient survives the initial months after transplantation.

Adult↗

Pure red-cell aplasia of long duration after major ABO-incompatible bone marrow transplantation.

We describe a patient with an exceptionally long-lasting red-cell aplasia of 330 days following ABO-incompatible bone marrow transplantation (BMT). Before BMT, the anti-B titre was high, 1:1,024, and it was only temporarily reduced by extensive plasma exchange. The anti-B titre remained above the level of 1:64 for 270 days, and host-derived isoagglutinin could still be detected 3 years after BMT. In vitro bone marrow cultures during the red-cell aplasia showed greatly reduced numbers or total absence of CFU-E, while the number of BFU-E colonies was only moderately subnormal. Six years after BMT, bone marrow and peripheral-blood cell counts are normal.

ABO Blood-Group System↗

Cardiac involvement in bone marrow transplantation: electrocardiographic changes, arrhythmias, heart failure and autopsy findings.

In order to evaluate cardiac involvement in bone marrow transplantation (BMT) we reviewed serial electrocardiograms, chest X-rays and cardiac pathology at autopsy in 45 consecutive adult patients undergoing BMT for hematologic malignancies at our institution. All patients were pretreated with cyclophosphamide (CY, 120 mg/kg) and total body irradiation (TBI, 10-12 Gy). A total of 15 patients developed electrocardiographic ST-segment or T-wave changes and/or arrhythmias post-BMT; four of them also suffered from congestive heart failure. The arrhythmias included frequent ventricular extrasystoles (two patients), paroxysmal atrial fibrillation (one patient), repeated supraventricular tachycardia (one patient) and QT-prolongation with ventricular tachyarrhythmias (one patient). Twelve patients showed an early drop of the total QRS voltage sum exceeding 15% of the pretransplant reading. In a subgroup of five patients the voltage drop was associated with ST-segment or T-wave changes; three of them developed congestive heart failure. At autopsy in 15 patients, the heart weight was on the average 113% of predicted. Myocardial edema, fibrosis and cellular hypertrophy were the most common microscopic findings. Two patients had marantic endocarditis of the aortic valve. Thus, in our experience clinically significant heart involvement affects 5-10% of patients undergoing BMT after pretreatment with CY and TBI. While cardiac complications are generally not a major problem of BMT, they may have serious consequences for individual patients and should therefore be carefully watched for in the treatment of BMT recipients.

Adolescent↗

Use of bronchoalveolar lavage cytology and determination of protein contents in pulmonary complications of bone marrow transplant recipients.

Bronchoalveolar lavage (BAL) cytology and immunoglobulin components of lavage fluid were studied during non-bacterial/non-fungal interstitial pneumonitis, bacterial/fungal pneumonia, and Pneumocystis carinii infection. Lavages done before bone marrow transplantation and in asymptomatic phases were used as controls. The total cell recovery was increased during lung processes of any aetiology. Non-bacterial/non-fungal pneumonitis caused a significant increase in the number of lymphocytes; the number of neutrophils increased particularly during bacterial pneumonia. In Pneumocystis carinii pneumonia the typical cell picture was an increased percentage of lymphocytes together with blasts. During acute graft-versus-host disease without respiratory symptoms the cytology in lavage fluids did not differ from the controls. Cytomegalovirus (CMV) isolation was frequently positive in lavage fluids regardless of the presence or absence of pulmonary symptoms, but most of the symptom-free CMV-positive patients did not have any marked changes in BAL cytology. The albumin content of BAL fluid increased during infectious and immunological processes in lungs.

Bone Marrow Transplantation↗

Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group.

Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Fatal rhabdomyolysis as a complication of bone marrow transplantation.

We describe fatal rhabdomyolysis in a 24-year-old man who had received a bone marrow transplant from a sibling for the treatment of chronic granulocytic leukaemia. The rhabdomyolysis was preceded by a grand mal seizure probably caused by a combination of cyclosporin A and corticosteroids given for the prevention and treatment of acute graft-versus-host disease.

Acute Disease↗

Heme therapy.

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Arginine↗

Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy.

Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD.

Acute Disease↗

Haem arginate treatment for hereditary sideroblastic anaemia.

It has been shown that haem arginate treatment increases blood cell counts, improves the sideroblast status of the bone marrow and normalises decreased activities of haem synthesising enzymes in some patients with acquired sideroblastic anaemia, or with other types of myelodysplastic syndromes. 4 patients with hereditary sideroblastic anaemia (HSA), belonging to two families, were therefore treated with haem arginate infusions, 3 mg/kg, on 4 consecutive days, and thereafter weekly for 10 wk. No effect was observed on the mildly anaemic haemoglobin levels or on the red cell counts. However, the initially low or low-normal myeloid to erythroid ratio in the marrow increased in all patients. A consistent decrease in the percentage of ring sideroblasts and other abnormal sideroblasts was seen in 1 patient (Family A), and a temporary decrease of abnormal sideroblasts took place during the most intensive treatment period in 2 other patients (Family B). Two of three initially abnormal haem synthesising enzyme activities became normal in Family A, whereas no clearly consistent effects on the haem synthesising enzymes were observed in Family B. The present study shows that haem arginate infusions can normalise the activities of haem synthesising enzymes in some patients with HSA. Further studies are needed to evaluate the impact of haem infusions on the iron balance of these patients.

Adult↗

In situ hybridization using a Y-specific probe--a sensitive method for distinguishing residual male recipient cells from female donor cells in bone marrow transplantation.

A non-radioactive in situ hybridization method was used to detect residual host cells after bone marrow transplantation (BMT). A biotinylated Y-specific DNA probe was hybridized to bone marrow cells of three male patients who had received a bone marrow graft from their sisters for the treatment of acute leukaemia. Host cells were detected in two of the three patients, both in clinical remission, in six and seven cells out of 1000 cells analysed, respectively. Only one of a total of 3000 cells from three female controls showed a 'Y-signal'; 2580 cells out of a total of 3000 cells from three male controls showed a positive signal. These results indicate that in situ hybridization is a reliable and sensitive method for the detection of host cells after BMT.

Adolescent↗

Effect of exogenous heme on hepatic iron-load and changes induced in hepatic heme metabolism by chronic iron-load.

It has recently been shown that heme arginate treatment can markedly improve blood cell counts in some severely cytopenic patients with a myelodysplastic syndrome (MDS). As MDS is often associated with iron overload, we have now studied in iron-loaded rats the hepatic effects of heme arginate given in a dose of 1.2 mg/100 g intraperitoneally twice a week for a period of 4.5 weeks. The heme injections caused a very marked increase in the mean hepatic iron content of the iron-loaded rats, which was more than twice the total amount of the heme-iron injected per rat. The heme treatment did not significantly affect the activities of the enzymes involved in the heme metabolism. Although no clinical side effects have been found in the MDS patients treated with heme arginate so far, the present study suggests that in iron-load the possible adverse hepatic effects should be taken into account and a minimum therapeutic dose of heme arginate should be used.

Animals↗

Heme arginate treatment for myelodysplastic syndromes.

Heme arginate was given to 26 patients with a myelodysplastic syndrome (MDS) as infusions of 2-3 mg/kg body weight weekly for 8-12 weeks. Most of the patients first received a loading dose on four consecutive days. Six of the patients showed improvement in cytopenias during the therapy. In three of the responders severely depressed blood cell counts recovered to normal or close to normal. So far the maximum duration of a response after the cessation of the treatment is 25 months, and the two ongoing responses have lasted for 11 and 12 months, respectively. In two responders of the eight patients with more than 15% ring sideroblasts the number of ring sideroblasts decreased during the treatment but remained unchanged in six non-responders. The responders were characterized by a low or low normal heme synthase activity which increased during the treatment, whereas the non-responders showed a higher mean heme synthase activity which decreased during the treatment. In general, the responders had significantly fewer defects in heme synthetic enzyme activities than the non-responders. FAB type, karyotype or growth pattern in in vitro cultures of hematopoietic progenitors did not predict the response. Apart from one case of mild venous irritation, no other adverse effects were seen. The present study shows that heme arginate induces beneficial effects on cytopenia in some MDS patients and has very few side-effects.

Adult↗

Heme arginate: effects on hemostasis.

Hematin, the drug used for acute porphyric attacks, has been shown to cause disturbances in hemostasis, mainly because of its degradation products. Lately a new heme compound, heme arginate, has been developed for the treatment of porphyrias. In experimental animal studies as well as in clinical use it has proved to be well tolerated. To find out whether heme arginate has any effects on hemostasis we have studied a number of parameters of coagulation and fibrinolysis after a heme arginate infusion in seven healthy volunteers. All parameters studied remained practically unchanged except the coagulation factor X, which showed a transient, insignificant decrease during the maximal heme concentration. We believe that the lack of side effects is due to a better stability of heme arginate, the degradation rates being 1% for heme arginate and 61% for hematin in four hours. Our data favor the use of heme arginate in acute porphyrias as well as in other deficiency states of heme.

Adult↗