What''s new in syndactyly?

The collection of peripheral blood stem cells (PBSC) is a crucial step for successful PBSC transplantation. Routine hematological parameters utilized for predicting the optimal timing of collection include white blood cell (WBC) counts, high fluorescence ratio (HFR) of reticulocytes, and platelet counts. We compared these parameters with the CD34-positive rates in the peripheral blood. In regimen with high-dose chemotherapy where the WBC count at nadir was lower than 1,000/microliter, we found that the maximum mobilization of PBSC was observed on the day when the WBC count reached 10,000/microliter. This coincidence was within about one day (mean 0.44, standard deviation 0.53). However, the reliability of the WBC count as a marker of PBSC mobilization varied among different harvest regimens. In the regimen with regular-dose chemotherapy where the WBC count at nadir was above 1,000/microliter, we could not find such a tight coincidence between the WBC count and PBSC mobilization. These results suggested that, in some situations, the measurement of the CD34-positive rate is mandatory for an efficient PBSC collection. We also found that the number of CD34-positive cells in the peripheral blood correlated (x) well to the amount of the CD34-positive cells actually harvested (y) (y = 0.524x + 0.249, r = 0.787). Thus, rapid fluorescence activated cell sorter (FACS) analysis of peripheral CD34-positive rates seemed to be extremely useful to predict the yield of PBSC collection.     

Immunocytologic detection of isolated tumor cells in bone marrow of patients with squamous cell carcinomas of the head and neck region

Methimazole 5 mg three times daily was prescribed in 1994 spring to a woman, aged 53 years, with relapsed hyperthyroidism. The drug was discontinued six weeks after initiation because of leukopenia. Two weeks still later, the patient developed chills, high fever, and a sore throat. The leukocyte count was 1,100/mm3 with 23% granulocytes, 76% lymphocytes and 1% monocytes. The granulocyte count stopped decreasing only three weeks after the drug was discontinued when the recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given; the patient recovered uneventfully. Thus we recommend that the peripheral leukocyte count of patients who receive methimazole therapy must be carefully monitored during the first three months. Furthermore, the use of rhG-CSF for methimazole-induced agranulocytosis abbreviates the period required for marrow recovery after cessation of this offensive drug.     

High levels of interferon alpha in the sera of children with dengue virus infection

We measured the levels of interferon alpha (IFN alpha) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFN alpha in dengue virus infections of humans. The percentage of patients who had detectable levels of IFN alpha (> or = 3 U/ml) was higher in patients with DHF (80%, P < 0.001) and in patients with DF (60%, P < 0.001) than in healthy Thai children (7%). The levels of IFN alpha were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFN alpha in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFN alpha after defervescence. However, the levels of IFN alpha in patients with DF were not high after fever subsided. The levels of IFN alpha were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFN alpha producers than in low IFN alpha producers. These results indicate that similarly high levels of IFN alpha are produced in vivo during the acute stages of DHF and DF, and that high levels of IFN alpha remain after fever subsides in some patients with DHF, but not in patients with DF.     

Abciximab-induced thrombopenia during treatment of acute coronary syndromes by angioplasty

ReoPro (abciximab) is the Fab fragment of a chimeric monoclonal antibody directed against platelet glycoprotein IIb-IIIa. Its efficacy to prevent ischaemic complications after PTCA has been demonstrated in 3 studies: EPIC, EPILOG, UPTAKE. One hundred and sixty five cases of thrombocytopenia (< 100,000/microliter) were reported in a series of 5461 patients randomized in these 3 studies (i.e. 3.0%), including 46 (2.03%) with placebo and 119 (3.73% with abciximab. Among the 2270 patients randomized to receive placebo, 11 (0.48%) cases of severe thrombocytopenia (< 50,000/microliter) were observed versus 34 (1.07%) with abciximab. Major acute thrombocytopenia (< 20,000/microliter and < 24 hours) occurred in 0.60% (20 patients) of cases with abciximab. Their mechanism remains unknown. A therapeutic challenge did not modify either their incidence, or their severity. The development of thrombocytopenia did not worsen the patient's prognosis and course was always favourable. Twenty five cases of thrombocytopenia (0.60%), including 3 cases of acute major thrombocytopenia (0.08%) were spontaneously reported in France among the first 4000 patients treated with abciximab post-marketing. All patients treated with abciximab must be monitored by platelet count, 2 to 4 hours after the bolus administration, then 12 and 24 hours later. These platelet counts should be performed on 3 tubes (EDTA, citrate, heparin) in order to eliminate pseudothrombocytopenia and a differential diagnosis. In the case of true thrombocytopenia (< 10,000/l), treatment should be suspended and the platelet count should be repeated daily until return to normal. In the case of thrombocytopenia less than 60,000/microliter, heparin and aspirin should also be systematically discontinued and, below 50,000/microliter, platelet transfusion is justified.     

An autopsy case of fungal (Mucor) cerebral aneurysm

An autopsy of rupture of Mucor cerebral aneurysm, not diagnosed during the patient's life, was experienced. A 63-year-old female was admitted to our hospital with the chief complaint of disturbance of consciousness and high fever. Her past histories were diabetes mellitus, liver cirrhosis and nasal sinusitis. The remarkable findings on admission were moderate inflammatory data, high blood sugar level in serum and ascites. Brain CT film revealed a non-enhanced low-density area in the frontal region. The cerebrospinal fluid showed bloody color and white blood cell counts were 3300/microliter (mostly neutrophils). Under our suspected of bacterial encephalomeningitis, intravenous cefotaxime and ampicillin therapy was started immediately. Cultures of cerebrospinal fluid for bacteria were negative. The disturbance of her consciousness gradually improved under general treatment. However, her conscious level suddenly became a coma on the 6th hospital day and she died on the 9th hospital day. An autopsy revealed Mucor at the site of the rupture of the cerebral aneurysm.     

Meeting women''s need for a flexible abortion service: retrospective study of a specialist day-care unit

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNalpha, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC) <10 x 10[9]/l which was induced by the pretreatment with hydroxyurea. One patient completed the 12th course of ATRA maintaining WBC <10 x 10(9)/l, platelets <500 x 10(9)/l and spleen not palpable. The treatment with ATRA was well tolerated and only one patient discontinued the therapy because of non-hematological side-effects. The area under the concentration-time curve (AUC) decreased significantly (P< 0.001) during the first week of therapy. By adopting an intermittent dosing regimen, 1 week on/ 1 week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs equivalent to the ones achieved on day 1 of course 1. In conclusion, our results showed that ATRA alone appeared to be unable to control the WBC expansion in the CML patients in chronic phase. Moreover, it did not induce any remarkable cytoreductive effects on the platelet count and on the hemoglobin level. The major interest of ATRA would be in combination with other therapies. If ATRA was given in combination with IFNalpha or other agents, dose reduction of these would not be planned. On the basis of the pharmacokinetic profile, ATRA should be administered intermittently rather than continuously.     

Rhabdomyolysis in antiretroviral therapy with Lamivudin

HISTORY AND CLINICAL FINDINGS: Six weeks after antiretroviral treatment with lamivudin (a nucleoside analogue) had been started (300 mg daily) in a 31-year-old man with AIDS developed pain and weakness in his muscles. On admission he had myalgia on pressure and movement as well as weakness of the entire body musculature, especially of the arms. The history and findings suggested bacterial or HIV-associated myositis. INVESTIGATIONS: Creatinekinase activity (4442 U/l) and myoglobin concentration (3250 micrograms/l) were greatly increased, while creatine (96 mumol/l) and C-reactive protein (22 mg/l) levels were only slightly raised. Serology was negative for acute and bacterial infections and autoimmune myositis. Magnetic resonance imaging and biopsy indicated marked rhabdomyolysis without myositis. DIAGNOSIS, TREATMENT AND COURSE: After excluding other causes, lamivudin and other drugs were discontinued, drug-induced rhabdomyolysis being suspected. This and the administration of prednisolone (100 mg daily) improved the symptoms. Creatinekinase activity and myoglobin level became normal within 14 days. On renewed administration of lamivudin creatinekinase and myoglobin concentrations in serum doubled to 180 U/l and 110 micrograms/l, respectively. Cessation of medication once again restored them to normal. CONCLUSION: Rhabdomyolysis is a serious but rare side effect of lamivudin treatment. Appropriate biochemical monitoring should therefore be undertaken when it is used in the treatment of HIV-positive patients.     

Gabexate mesilate induced recovery from thrombocytopenia in a patient with acute ITP

A 47-year-old woman was admitted to our hospital complaining of subcutaneous hemorrhages. She had taken medicine because of a common cold one month before admission, and two weeks after that, she noticed the hemorrhagic diathesis. Laboratory data on admission were as follows; 1,000/microliters of platelet count (PLT), normal myelogram, normal coagulation tests, positive PAIgG and anti-platelet antibody. She was diagnosed as idiopathic thrombocytopenic purpura and a standard dose of prednisolone was started immediately. However, on the 3rd hospital day (HD), frequent hematemesis from submucosal hematomas developed. Pulse therapy of methylprednisolone and immunoglobulin therapy were ineffective. From the 15th HD slow drip infusion of vincristine and continuous drip infusion of 1, 500 mg/day of gabexate mesilate (GM) were started. Because PLT increased to 85,000/microliters and hematemesis disappeared on the 22nd HD, GM was discontinued. However on the 25th HD, PLT decreased to 1,000/microliters again. After re-starting GM, PLT was maintained at over 100,000/microliters. Subsequent examinations ruled out collagen diseases but revealed that she had Hashimoto's thyroiditis. We concluded that the complement inhibitory action of gabexate mesilate might have contributed to PLT increase in this case, as has been previously reported in three other cases.     

Interferon-alpha and hydroxyurea in early chronic myeloid leukemia: a comparative analysis of the Italian and German chronic myeloid leukemia trials with interferon-alpha

In 1994, the Italian and the German Chronic myeloid leukemia (CML) trials comparing interferon-alpha (IFN-alpha) with conventional chemotherapy were published. The survival advantage in favor of IFN-alpha compared with hydroxyurea (HU; 72 v 52 months) was significant in the Italian (P < .002), but not in the German trial (66 v 56 months, P < .44). We set up a collaborative study to identify the reasons for the different outcomes. There are major differences in the trial protocols concerning admission criteria, treatment strategy, and definitions. The German patients were older and more seriously sick. Fifty-two of the 327 patients in the German IFN and HU arms did not fulfil Italian admission criteria, and 41 of the 322 Italian patients did not fulfil German admission criteria. Using mutually uniform admission criteria, the median survival times of the IFN patients are 76 (Italian) and 72 (German) months (P = .56). The Italian group administered IFN combined with HU as needed, whereas the German group strictly used IFN as monotherapy with rerandomization to busulfan (BU) or HU after IFN resistance or intolerability. The differences seen between the Italian and the German trial results can be accounted for by objective differences in study design, especially the admission criteria, treatment strategy, and bias due to intention to treat analysis. The detailed analysis of the data suggests that the combination of IFN with HU as needed is more effective than either agent alone.     

High-dose cladribine therapy for chronic myelogenous leukemia in the accelerated or blast phase

PURPOSE: A phase II clinical trial was performed to evaluate the effectiveness of high-dose cladribine (2CDA) for treatment of chronic myelogenous leukemia (CML) in the accelerated or blast phase. PATIENTS AND METHODS: Nineteen patients were treated. The median age was 55 years (range, 30 to 73). Six were older than 60 years. Eight had progressed after intensive combination chemotherapy and three after allogeneic or autologous transplantation. For the first course, 16 patients received 2CDA at 15 mg/m2/d intravenously (i.v.) over 1 hour for 5 days. Two received 18 mg/m2 and one received 21.5 mg/m2 daily. The second course was escalated to 20 mg/m2/d in five patients. RESULTS: Rapid cytoreduction of leukemia occurred in the blood, with the nadir at 10 to 12 days. The median WBC count decreased from 36,900/microL before treatment to 500/microL at the nadir and recovered to 5,200/microL at day 30. The median platelet count changed from 113,000/microL to 24,000/microL at the nadir and 71,000/microL at day 30. The complete remission (CR) plus partial remission (PR) rate was 47% (95% confidence interval [CI], 23% to 72%). One 64-year-old man with lymphoid blast phase of CML had a morphologic and cytogenetic CR that lasted 9 months. The median survival for all patients was 34 weeks, and the median survival for the eight responders was 56 weeks (range, 11 to 167). The median number of days spent in hospital over the entire treatment period was 19 (range, 4 to 60). CONCLUSION: High-dose 2CDA therapy provides effective palliation for CML in accelerated or blast phases, even for heavily pretreated patients.     

Hyperdynamic hemodynamics following high-dose interleukin 2-interferon alpha therapy in patients with metastatic renal cell carcinoma. Immunotherapy as a clinical sepsis model?

Human recombinant interleukin 2 (IL-2), alone or in combination with other cytokines, is currently under investigation for the immunotherapy of metastatic tumours. Objective responses of 20-35% have been reported in patients with disseminated melanoma and renal cell carcinoma who received high-dose intravenous IL-2 in combination with interferon-alpha (IFN alpha). However, treatment with IL-2 is complicated by a syndrome of life-threatening adverse reactions such as disseminated vascular leakage, fluid retention, severe hypotension, and (reversible) multiple organ dysfunction (MODS). A systemic inflammatory reaction (SIRS/sepsis sepsis-like haemodynamic pattern has been described in patients after IL-2 bolus application alone. Our purpose was to study the haemodynamic changes in patients treated with high-dose IL-2 administered as a constant infusion and in combination with IFN alpha. PATIENTS AND METHODS: Haemodynamic variables were obtained during therapy courses of 11 patients (aged 48 to 71 years, median 61) with metastatic renal cell carcinoma receiving immunotherapy with IL-2/IFN alpha. Therapy consisted in IFN alpha 10 x 10(10) IU/m2 body surface area (BSA) once daily on days 1-5 i.m. on a regular ward, followed by IL-2 as a constant infusion of 18 x 10(6) IU/m2 BSA on days 6-11 in an intensive care unit (ICU). Haemodynamics were first measured after 5 days of IFN alpha application and transfer to the ICU on day 6, a further 24 h after the beginning of IL-2 infusion (day 7), and the end of the therapy course (days 10 and 11). Mean arterial pressure (MAP) was measured noninvasively using an oscillometric device (Dinamap, Critikon). Mixed-venous oxygen saturation (sv O2) was measured using an CO-oxymeter (OSM 3, Radiometer) and peripheral arterial oxygen saturation (psaO2) was recorded continuously with a pulse oximeter (Oxyshuttle, Critikon). In case of haemodynamic instability, stabilisation had priority over invasive haemodynamic measurements, so that nadir values of blood pressure (BP) did not influence mean MAP and are reported separately. Lactate values and criteria for SIRS were obtained before and during IL-2 infusion. Lactate measurements were performed using an enzymatic essay (Abbot FLx). The mean effect size of the haemodynamic values, SIRS criteria, and lactate concentrations during IL-2 infusion (days 6-11) were calculated, and 95% confidence intervals for the effect sizes are indicated. RESULTS: After their daily i.m. injections of IFN alpha, patients had short episodes of fever and tachycardia without significant drops in BP. A few hours after transfer to the ICU and continuous infusion of IL-2, they developed a syndrome of fever, tachycardia and tachypnoea. The haemodynamic values after 5 days of IFN alpha therapy remained in the normal range, whereas those during IL-2 infusion strongly resembled SIRS and sepsis, with a decrease in MAP (98 to 28 mm Hg) and systemic vascular resistance (SVR, 1477 to 805 dyn.s.cm-5) and an increase in cardiac output (cardiac index 2.8 to 4.3 l.min-1.m-2). MAP often had to be stablilized with colloids during the last 48 h of therapy; 5 patients had nadir values below 60 mm Hg, or 30% below basic values in hypertensive patients. Catecholamine therapy became mandatory in 1 patient and therapy had to be discontinued. Surprisingly, some patients already had elevated plasma lactate concentrations after IFN alpha therapy. During IL-2 infusion mean plasma lactate levels increased from 2.3 to 3.2 mmol.l-1 and all patients had lactate concentrations above 2.0 mmol.l-1 at the end of therapy. During the last 48 to 72 h of IL-2 infusion, patients suffered from MODS with altered mental state (7 patients), oliogoanuria (all patients), cardiac dysrhythmias (4 patients), congestive heart failure (1 patient, which led to a second case of therapy interruption), elevated bilirubin (4 patients), and pulmonary dysfunction. In 9 patients supplementary oxygen was necessary when psaO2 fell below 92     

Influence of cardiopulmonary bypass on lymphocyte function

It is known that lymphocyte function is impaired after cardiopulmonary bypass (CPB). In this study, the lymphocyte stimulation test (LST) with PHA was used before and after CPB in 28 adult patients, and compared with the surgical parameters and serum cytokine (IL-6, IL-8) levels. LST was impaired after CPB in all patients. Although this value usually recovered by the third postoperative day (POD); (normal group, n = 16), some patients showed prolonged duration of the impaired LST (delayed group, n = 12). Therefore, the parameters of surgery, white blood cell (WBC) count, lymphocytes and subsets, and serum cytokine levels were compared between the normal and the delayed groups. There was no significant difference in the number of WBCs or lymphocytes between these two groups. OKT4-positive cells were reduced on the first POD in both groups, and in the normal group, the number of OKT4-positive cells recovered more quickly than in the delayed group. Serum IL-6 and IL-8 levels in the delayed group were elevated after CPB, and were significantly higher in the delayed group than in the normal group. In conclusion, patients who showed prolonged impairment of lymphocyte function may be partly due to prolonged CPB.     

Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia

A 35-year-old man with non-Hodgkin's lymphoma (NHL) (follicular small cleaved, B cell, stage IVB) received double myeloablative chemotherapy with syngeneic peripheral blood stem cell transplantation (PBSCT). Although platelet recovery was delayed until day 29 after the second transplantation, thereafter trilineage hematopoietic reconstitution was achieved. The evaluation after PBSCT did not detect any residual tumor. The patient was in good health until day 138, when his platelet count suddenly began falling; on day 150, it had fallen to 1.5 x 10(4)/microliter, and the patient was re-admitted for treatment. The bone marrow was normocellular with a normal count and megakaryocyte structure. Other examinations, including serological tests and computed tomography of the neck, chest, abdomen, and retroperitoneum, did not indicate a recurrence of NHL or reveal the cause of thrombocytopenia. The patient's platelet-associated IgG (PAIgG) level was at 70.9 ng/10(7) platelets (normal range: 9-25 ng/10(7) platelets); a diagnosis of thrombocytopenia due to an autoimmune mechanism such as idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone therapy increased the platelet count and reduced the PAIgG level. Thrombocytopenia with an ITP-like mechanism rarely occurs more than 100 days after autologous or syngeneic stem cell transplantation, and should be taken into consideration as a late complication of PBSCT.     

A case of AIDS with disseminated Mycobacterium kansasii infection in which Mycobacterium, avium complex was also detected from his sputum repeatedly

A 43 year-old Japanese male was admitted to our hospital because of productive cough and fever. He was diagnosed as acquired immunodeficiency syndrome (AIDS) in 1994. Laboratory findings were as follows: WBC was 3200/microliter, CD4+ T lymphocyte count was 22/microliter. His chest X-ray film taken on admission showed infiltration with small cavity lesion in middle left lung field. Tuberculin skin reaction was negative. He was treated with isoniazid 0.4 g, rifampicin 0.45 g, and ethambutol 0.75 g each daily. Sputum smear was positive for acid fast bacilli. The cultured isolates were identified as Mycobacterium kansasii (M. kansasii) and Mycobacterium avium complex (MAC). Urine smear was also positive for acid fast bacilli. The cultured isolates were identified as M. kansasii. He was diagnosed as disseminated M. kansasii infection and suspected MAC infection. About one hundred days later, his chest X-ray film showed reticular shadow. His clinical symptoms improved and the sputum smear and culture converted to negative for acid fast bacilli. Based on these findings, his MAC discharge was considered not as MAC infection, but MAC colonization. He returned to the former hospital for AIDS treatment, and he died in August 1996.     

Mycotic renal artery degeneration and systemic sepsis caused by infected renal artery stent

A case of Staphylococcus aureus renal artery stent infection was studied. Fourteen days after the procedure, the patient had a fever, hypotension, and an elevated white blood cell (WBC) count. Blood cultures were positive for S. aureus on admission and during the patient's hospitalization, despite intravenous vancomycin therapy. Evaluation included serial CT scans, revealing increasing persistent inflammation with development of multiple renal intraparenchymal abscesses, and arteriography, showing marked degeneration of the renal artery. Therapy required resection of the renal artery/stent and nephrectomy. This case confirms the severe nature of S. aureus stent infection; we recommend prophylactic antibiotics before these procedures, as well as expeditious evaluation and consideration for aggressive surgical therapy if this complication is suspected.     

Impaired mobility: Guillain-Barré syndrome

Blood endotoxin concentrations measured in 57 patients with digestive disorders pre- and postoperatively, were found to peak one day after surgery, then gradually return to the preoperative level. The plasma endotoxin concentration was not significantly different in patients with and without liver cirrhosis before surgery, but was significantly higher in the cirrhosis group one day after surgery. The preoperative endotoxin concentration did not correlate with the white blood count (WBC), platelet count, or routine biochemical liver function tests, however, a significant negative correlation was observed between the plasma endotoxin and fibronectin concentrations. The ability of plasma to inactivate endotoxin was quantified by serial measurements of the endotoxin concentration following the addition of a known quantity to each patient's plasma. The plasma from normal subjects quickly inactivated endotoxin, but inactivation was decreased in the plasma from patients with liver failure.     

Cellular pharmacodynamics and plasma pharmacokinetics of parenterally infused hydroxyurea during a phase I clinical trial in chronic myelogenous leukemia

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and antileukemic activity of hydroxyurea (HU) administered intravenously to patients with advanced-phase chronic myelogenous leukemia (CML). Further objectives were to analyze pharmacodynamic effect on deoxynucleotides (dNTPs) and to seek relationships between the decrease in dNTP pools and inhibition of DNA synthesis in CML blasts. PATIENTS AND METHODS: HU (8, 12, 18, 27, and 40 g/m2) was administered intravenously by a 24-hour continuous infusion to 19 adults with CML in blastic or accelerated phase. Plasma levels of HU were analyzed in all patients. To determine the role of HU in inhibiting ribonucleotide reductase, dNTP pools in the leukemia cells were quantitated. Correlations were sought with these parameters and DNA synthesis inhibition measured ex vivo by [3H]thymidine incorporation. RESULTS: The MTD of HU given as a 24-hour infusion was 27 g/m2. The dose-limiting toxicity was mucositis. There was a significant but transient myelosuppression, with nadir counts generally seen 3 to 4 days after the dose. The steady-state concentration of HU in plasma was achieved by 6 hours, and was proportional to the dose. There was a median 57% decrease in the deoxyadenosine triphosphate (dATP) pool in circulating blasts. In contrast, deoxyguanosine triphosphate (dGTP) and pyrimidine dNTPs were not significantly affected. The extent of DNA synthesis inhibition was related to the residual concentrations of intracellular dATP. CONCLUSION: A 24-hour infusion of HU results in significant but transient myelosuppression in advanced-phase CML. The specific decrease of intracellular dATP correlated with the inhibition of DNA synthesis in CML blasts. This pharmacodynamic action of HU provides a rationale for combination with other chemotherapeutic agents, the effects of which could be augmented by the decline in dATP pools.     

Chronic myelomonocytic leukemia with repeated respiratory failure associated with leukocytosis following splenic arterial embolization and splenectomy

A 32-year-old female was admitted due to splenomegaly and leukocytosis in September, 1993. The leukocyte count was 26,900/microliter with 29% monocytes (7,800/microliter). A diagnosis of the chronic phase of chronic myelomonocytic leukemia was made. On November 19, 1993, splenic arterial embolization was performed. After the embolization, the leukocyte count rapidly increased, and acute respiratory failure developed. The respiratory condition was improved by methylprednisolone (m-PRED) pulse therapy. Subsequently, the effectiveness of chemotherapy gradually decreased, and there was an increase in the leukocyte count. Respiratory failure developed again but was successfully treated with m-PRED pulse therapy in addition to aclarubicin. On July 4, 1995, splenectomy was performed. The leukocyte count rapidly increased, and acute respiratory failure again developed. She did not respond to m-PRED pulse therapy, but the respiratory condition was markedly improved by leukoplasmapheresis. The respiratory failure in this patient may be associated with capillary leak syndrome due to neutrophilia. In addition, stasis of increased monocytes in the pulmonary capillaries and their infiltration into the pulmonary parenchyma and alveoli was thought to have occurred.     

Interferon therapy for chronic myelogenous leukemia

Interferon alpha (IFN alpha) has been used in the treatment of chronic myelogenous leukemia (CML). The initial trial was made in 1983 by Talpaz et al. Their first report suggested that IFN alpha treatment could achieve high hematological remission. The cause of the effect was unclear, but may be mediated through interaction cell surface membrane and inhibitory protein production. IFN alpha was related to some T cell immunity, and could be taken to be Ph1 positive cell inhibition by normal T cell. Although IFN alpha therapy has limited use with get Ph1 negative hematopoiesis, intensive treatment of this kind is needed to minimize Ph1 clone, using various therapy combination with IFN alpha.     

Septic myocardial aneurysm in mitral valve endocarditis. Clinical and pathological-anatomical findings

HISTORY AND CLINICAL FINDINGS: A 68-year-old woman was hospitalized because of fever and tiredness for 3 months. Her general condition was clearly impaired. She had a mild fever of 38.5 degrees C and on auscultation a 3/6 systolic murmur, maximal parasternally in the 3rd intercostal space, transmitted to the apex. There were distant rales over both lungs, the neck veins were distended and there was ankle oedema. INVESTIGATIONS: C-reactive protein was raised to 17.3 mg/dl (normal up to 0.9 mg/dl), WBC count 19,300/microliter. beta-haemolysing streptococcus (S. agalactiae) was grown in the blood culture. The ECG showed sinus tachycardia (rate of 98/min) and transthoracic echocardiography demonstrated a small pericardial, enlarged ventricles, marked mitral regurgitation and a large vegetation on the posterior mitral leaflet, as well as a 3 x 4 cm mass in the posterior wall of the ventricle, originating from the posterior mitral valve ring and communicating with the vegetation on the mitral valve. The posterior mitral leaflet was perforated. TREATMENT AND COURSE: As endocarditis of the mitral valve with a complicated course was suspected-abscess of the posterior mitral valve ring and septic myocardial aneurysm with associated pericarditis and haemodynamically insignificant effusion-she was transferred to the intensive care unit where she died suddenly of circulatory arrest only 30 min after transfer. Autopsy confirmed the echocardiographic findings. CONCLUSION: Paravalvular abscess in the course of mitral valve endocarditis is rare, but should be looked for at transthoracic echocardiography so that any necessary surgical intervention can be undertaken early.