Complications due to abandoned noninfected pacemaker leads.

Noninfected unwanted pacemaker leads are usually abandoned since the reported complication rate related to them is low. We followed 60 patients with noninfected retained leads, and complication was observed in 12 (20%) of them. Lead migration occurred in 5 patients, skin erosion in 3 patients, venous thrombosis in 2 patients, and muscle stimulation in 2 patients. Management of the complications was a surgical procedure in seven patients, including two cases of open heart surgery, while chronic medical treatment was necessary in the other five patients. The results of this study suggest that complications due to noninfected abandoned leads may not be as rare as it was previously thought and may present a significant morbidity and cost burden. With the lead extraction technique available, the issue of the removal of all unwanted pacemaker leads should be addressed.

[Detection of minimal residual diseases in B-cell tumors using PCR specific for the immunoglobulin heavy chain gene]. / A minimális reziduális betegség kimutatása B-sejtes tumorok esetében az immunglobulin nehézlánc génre specifikus polimeráz láncreakció segítségével.

In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To explore clinical usefulness of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in the detection of MRD a follow up study of 10 patients with B-cell NHL have been performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense primer specific for the heavy chain variable region (VH) and antisense primer specific for the heavy chain joining region (JH) of the IgH gene. The clonal rearrangement of IgH gene detected by PCR was used as clonal marker to determine MRD after treatment. In three cases, where clinical remission was not achieved, clonal IgH gene rearrangement was detected after the treatment. In seven cases, clinical remission was achieved after induction therapy but the PCR analysis revealed clonal IgH gene rearrangement in three of the cases. In all of the three cases, where MRD was detected by PCR, clinical relapse developed after 7-28 months of the therapy. In all cases that have relapsed, the IgH gene rearrangement was identical at the time of initial diagnosis and at the relapse. This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a useful method to monitor and detect MRD before clinical relapse.

[Long-term results with fludarabine monotherapy in chronic lymphocytic leukemia]. / Fludarabin monoterápiával kezelt krónikus lymphoid leukaemiás betegeink hosszú távú követése során szerzett megfigyeléseink.

Fludarabine has widely been studied in chronic lymphocytic leukemia (CLL), with impressive remission rates in refractory, relapsed or untreated disease. In our study the clinical response and survival of 9 patients with a mean follow-up time of 28 months after treatment with fludarabine as a single agent for CLL has been evaluated. Seven patients were previously treated. Partial remission was achieved in 8 patients. No complete remission was seen. The cytoreductive activity of fludarabine was excellent in all the 9 patients. The median time to progression was 13.5 months. The median survival time from entering the trial was 27.9 months. Our patients tolerated the fludarabine treatment extremely well. Although fludarabine has been established as the most active single agent in CLL, most patients will have recurrent disease. 7/9 patients relapsed in our study, and they were given further chemotherapy. Grade 4 hematologic toxicity was observed in 2 patients. During the fludarabine treatment the frequency of infections decreased, but in the following 12 months increased again. Three fludarabine-treated patients developed high-grade non-Hodgkin lymphoma. It is concluded that fludarabine is a highly useful agent in CLL.

Responses to single-dose thrombopoietin decrease with higher platelet counts in mice.

Since the description of human thrombopoietin (TPO) we investigated the thrombocytosis-inducing capacity of human serum samples derived from individuals with altered thrombocytopoiesis. Several times the degree of thrombocytosis developing in recipient mice differed markedly even when applying the same human material. In the last 2 years, we applied single doses of recombinant human TPO (rHuTPO) to random-bred CFLP mice, and the same observation was made. Taken together with previous information (before 1970) it was possible to select cases in which the percent increases in circulating platelet counts inversely correlated with the starting levels. It appears, however, that apart from the known absorbing role of platelets and megakaryocytes, the response to single doses of exogenous rHuTPO in mice depends, at least partially, on an unknown endogenous homeostatic mechanism. Mixing thrombopoietically active human sera with platelet-free normal serum in a 1:1 ratio remarkably reduced the thrombocytosis-inducing capacity. Repeated pharmacological doses of TPO, applied in the majority of the reported trials, however, easily obscure the physiological control mechanism.

[Immune thrombocytopenic purpura and pregnancy: maternal risk factors]. / Immun thrombocytopeniás purpura és terhesség: az anya veszélyeztetettsége.

Authors analyse 75 pregnancies and 51 deliveries, respectively, of 45 mothers with chronic immune thrombocytopenia (ITP) from the point of view of maternal risks. Pregnancies that occurred in active disease were electively terminated. It was found that pregnancy contributed to the clinical manifestation of ITP, and antepartal bleeding took place in 18%, and preeclampsia emerged in 6%. The chronic ITP showed exacerbation during pregnancy in 27.3%, thus causing antepartal bleeding in 4.5% and postpartal bleeding in 15.9%. Postpartal bleeding presented in total 20%, not only in cases with severe ITP, but also in moderate ones. Postpartal blood transfusion was needed in 16%. The postpartal reduction of hemoglobin level determined 2-3 days following delivery was higher than in those ITP patients who had no postpartal haemorrhage than that in the general obstetrical population. This suggests an increased blood loss associated with delivery in patients with ITP. Maternal morbidity of patients with ITP in whom the disease first manifested during pregnancy was higher than that of those patients in whom pregnancy was associated with the remission of ITP. In order to decrease the maternal risks in ITP we advise that pregnancy should occur and be carried during remission.

Pregnancy in liver cirrhosis. Assessment of maternal and fetal risks in eleven patients and review of the management.

Eleven patients with liver cirrhosis who had a pregnancy between 1974 and 1992 are reported. Prior to pregnancy 2 patients were splenectomized, 1 of them also had an unsuccessful mesocaval shunt and therefore underwent sclerotherapy. Furthermore, 3 patients were managed by injection sclerotherapy, 6 patients had episodes of hepatocellular failure and 5 had signs of hypersplenism. Gastrointestinal hemorrhage associated with pregnancy was noted in 6 patients. Jaundice was encountered in 2 patients, a raised bilirubin level in 3, ascites in 3, impairment of the synthetic liver function in 5, thrombocytopenia in 8, hemorrhagic diathesis in 5, and infectious puerperal complication in 5 patients. Esophageal sclerotherapy was used in 5 and transfusion in 6 patients. Of 12 births, 6 newborns were small-for-date and 1 of them died. Three neonates were preterm. Fetal wastage did not occur. The present data suggest that gastrointestinal hemorrhage in liver cirrhosis contributes to developing fetal growth retardation; cirrhotic patients can be prepared for pregnancy and the hematemesis during pregnancy can successfully be managed by esophageal sclerotherapy.

Autoantibody occurrence in hairy cell leukemia.

BACKGROUND: Autoimmune syndromes accompanying hairy cell leukemia (HCL) may represent a specific entity in HCL patients. It has been claimed that interferon (IFN)-alpha therapy contributes to the occurrence of autoantibodies in HCL. The study was undertaken to determine the occurrence of autoantibodies in HCL patients prior to IFN-alpha therapy. PATIENTS AND METHODS: Sera of 24 patients with HCL of B-cell origin (as determined previously by peripheral blood mononuclear cell surface markers and/or DNA rearrangement studies) were investigated. In addition serum from a T-HCL patient was studied. Nineteen of the 25 HCL patients had been splenectomized prior to the study. One patient was found to have IgM lambda monoclonal protein in her serum. Antinuclear antibodies were determined with an indirect IF test using Hep-2 cells. Rheumatoid factors of the IgM and IgA classes were determined by enzyme-linked immunosorbent assay (ELISA). Granulocyte-specific antinuclear antibodies and antineutrophil cytoplasmic antibodies were determined by indirect immunofluorescence. RESULTS: No clinical syndrome of an autoimmune disease was apparent in any of our HCL-patients. Rheumatoid factors of either IgM or IgA class were found in the sera of six B-HCL patients and antinuclear antibodies in five cases, while anti-cytoplasmic antibodies were identified in only three cases. The occurrence of antibodies seemed to be independent of the clinical stage of the disease as determined according to the functional criteria. Two patients with arthralgias and one with vitiligo had no autoantibodies in their sera. CONCLUSIONS: Autoantibodies might occur in HCL patients prior to treatment with interferon-alpha and in the absence of the clinical syndrome of an autoimmune disease.

Splenic thrombosis complicating pregnancy in patients with poor obstetrical outcome. A report of four cases.

The association of pregnancy and splenic vein thrombosis is rare. The authors describe four patients who had acute painful splenomegaly in association with pregnancy. All patients had a slightly elevated platelet count in the nonpregnant state and had at least one spontaneous abortion. One patient had transient neurologic symptoms, and two others had a history of gastric ulcer. The splenic thrombosis occurred in the 9th (in two cases) and in the 13th week of gestation (in two cases), and 1 week after abortion (in two cases). Three patients underwent splenectomy and one refused it. All patients had persistent thrombocythemia after the splenectomy. In three patients the platelet count reversibly dropped at least 50% during pregnancy. Of their 19 pregnancies, one resulted in normal birth, one in preterm birth, two in therapeutic abortion, and 15 in spontaneous abortion. Data presented suggest that the latent form or early stage of a myeloproliferative disorder may contribute to both splenic and placental thrombosis.

Pregnancy and hereditary spherocytosis. Report of 8 patients and a review.

As there is only little information on pregnancy complicated by hereditary spherocytosis, we report on 8 patients with this disorder who had a total of 19 pregnancies. 10 pregnancies occurred in patients before splenectomy, and 9 occurred after splenectomy. There were 13 term births, 4 spontaneous abortions and 2 therapeutic abortions. Of the 19 pregnancies, 8 were complicated by anemia and all were in patients without splenectomy. A hemolytic crisis was encountered in 6 pregnancies, and persistent anemia occurred in 2. Transfusion was required in 4 pregnancies. It would appear that pregnancy may precipitate hemolytic anemia but maternal morbidity and fetal outcome seem more favorable after splenectomy than before splenectomy.

Pregnancy in idiopathic aplastic anemia (report of 10 patients).

This paper reports on 6 patients with severe, 2 with moderate and 2 with mild aplastic anemia who had a total of 18 pregnancies after the diagnosis. All four pregnancies that occurred during the active state of severe and moderate aplastic anemias were electively terminated. Two out of 14 pregnancies that occurred during the long-term remission were electively terminated for non-medical reason, two spontaneous abortions occurred and 10 live births were seen. All offspring were healthy at follow-up. During pregnancy the circulating blood cell levels decreased in 1 out of 6 pregnancies in patients who were in remission from mild and moderate aplastic anemias, and in 4 out of 8 pregnancies in patients who were in remission from severe aplastic anemia. In all 5 cases that showed a relapse during pregnancy the remission recurred following the termination of pregnancy. The data presented suggest that aplastic anemia in long-term remission can unpredictably relapse during pregnancy, but its final outcome appears not to be affected by pregnancy. Furthermore, there is no correlation between the pre-pregnancy clinical course and the events during pregnancy. The outcome of pregnancy during the remission of aplastic anemia seems beneficial, and spontaneous delivery should be preferred.

Differentiation and activation antigens on blood mononuclear cells in lymphocytic leukemia before and during IFN-alpha 2B therapy.

Expression of differentiation and activation antigens on peripheral blood mononuclear cells of four chronic lymphocytic leukaemia (CLL) patients was studied before and during interferon-alpha 2b therapy. Patients had clinical stage B(II) disease, a lymphocyte count of over 60 G/l and a lymphocyte doubling time shorter than 12 months. One of the patients unresponsive to previous chemotherapy experienced a substantial decrease of the lymphocyte count during interferon-alpha 2b (IFN-alpha 2b) therapy, with a nadir at one fifth of the initial value while on this therapy. The lymphocyte count decreased slightly in a further patient, while it increased in two patients. Treatment with IFN-alpha 2b left the phenotype of CLL lymphocytes essentially unchanged. The elevated serum beta-2 microglobulin values increased further during treatment with the exception of the CLL patient responsive to IFN-alpha 2b therapy. The clinical stage of the disease did not change in any of the patients when evaluated according to the criteria of the International Workshop on CLL. Further studies are necessary to determine which of the CLL patients benefit from therapy with interferon-alpha 2b.

Pregnancies and offspring in survivors of acute lymphoid leukemia and lymphoma.

Since few data on the reproductive outlook of patients successfully treated for lymphoproliferative disease are available, further experiences on the pregnancy outcome and offspring follow-up of 12 women treated for acute lymphoid leukemia and 7 women treated for malignant lymphoma are reported. Of the 20 pregnancies of leukemic patients in remission, 14 ended in live births, one in spontaneous abortion, and 5 in elective abortions among which one was performed during relapse. One minor (hip dysplasia) and one major birth defect (Apert syndrome) were seen. The Apert syndrome baby is considered as a new mutation. Of the 9 pregnancies of lymphoma patients 5 ended in normal births and 4 in elective abortions. Neither relapse nor malformation was encountered. One leukemic patient had gestational edema and one lymphoma patient had puerperal thrombophlebitis of lower extremity. The offspring of the above patients appropriately developed and had no complication except for one with cephalhematoma and for another one with epilepsy attributed to birth injury.

Immunoglobulin profiles and antibacterial antibody levels in hairy cell leukaemia.

Serum immunoglobulin and natural antibody concentrations to environmental antigens have been determined in 26 hairy cell leukaemia (HCL) patients. The serum IgG, IgA and IgM levels as well as the concentration of antibodies to the majority of intestinal bacteria were found to be normal in both groups of HCL patients. In contrast to the data on the impaired humoral immunity of chronic lymphocytic leukaemia (CLL) patients, our results show that in HCL the studied aspects of humoral immunity are normal. Serum IgE levels were found to be significantly decreased in HCL when all patients were taken as a group. The difference was due to the decreased serum IgE concentration of splenectomized HCL patients, while IgE levels of untreated HCL patients did not differ statistically from that of the healthy controls.

Characterization of T lymphocyte subsets in hairy cell leukaemia: influence of splenectomy and correlations with the clinical stage of the disease.

Peripheral blood mononuclear cell surface markers were studied in a series of 26 hairy cell leukaemia patients 19 of whom were splenectomized previously. Patients with non-symptomatic and stable disease were distinguished from those with symptomatic and/or progressive disease (also termed "active" clinical stages). In all HCL patients as a group, the absolute number of CD4+ MN cells did not differ statistically from that of the controls, while the number of CD8+ MN cells was significantly increased. The reduction of the CD4/CD8 ratio in the peripheral blood of HCL patients as compared to the controls was explained by the reduction of this ratio in patients with "active disease", while the CD4/CD8 ratio of patients with non-symptomatic and stable disease did not differ statistically from that of the controls. The CD4/CD8 ratio was found to be influenced mainly by the clinical stage of the disease, and not by the effect of splenectomy.

Peripheral blood leukocyte subpopulations a long time after posttraumatic splenectomy.

Peripheral blood leukocyte subpopulations have been determined in 50 patients a long time (2 to 20 years) after posttraumatic splenectomy. These otherwise healthy individuals had significant lymphocytosis and monocytosis, while the absolute number of granulocytes did not differ statistically from that of the controls. The absolute number of CD2+, CD3+ as well as CD4+ and CD8+ peripheral blood mononuclear cells was found to be elevated, while the number of CD21+, CD20+ and HLA-DR+ PBMN cells was significantly decreased. The absolute number of sIgM+ as well as CD16+ MN cells did not differ statistically from that of the controls. Two further patients were found to have developed B-chronic lymphocytic leukaemia 5 and 31 years following posttraumatic splenectomy, respectively.

Immunoglobulin profiles and antibacterial antibody levels in 50 patients a long time after posttraumatic splenectomy.

Serum immunoglobulin and antibacterial antibody concentrations have been determined in 50 patients 2 to 20 years after posttraumatic splenectomy. The serum levels of IgG, IgA and IgM were found to be significantly greater in the group of posttraumatic splenectomy patients than in that of the healthy controls. The serum IgE concentrations did not differ statistically from that of the controls. The serum level of natural antibodies against intestinal bacteria were found to be elevated (Shigella 1b, 2a, 3 and Salmonella typhi 02 strains) or normal (Salmonella typhi 0901 as well as E Coli 026 and 055 strains). Our results show that the studied functional aspects of humoral immunity in this group of otherwise healthy splenectomized individuals were not impaired.