Spurious platelet counts in acute leukaemia with DIC due to cell fragmentation

Automated platelet counts in a patient with newly diagnosed AML M5 with extreme leukocytosis were reported as 129, 166 and 121 x 10(9)/1. Routine blood films showed a corresponding number of platelet-sized particles, judged to be platelets. The patient was treated for DIC with low-dose heparin infusion. Platelet transfusions were not given initially. The patient died 14 h after admission from intracerebral haematoma. The origin of the platelet-sized particles seen in routine stained blood films was examined by cytochemical and immunological staining for peroxidase, non-specific esterase, CD 13 and CD 33. About 1/3 of the fragments had the same staining characteristics as the leukaemia cells, indicating leukaemia cell origin. Staining for platelet-specific antigen GpIIIa was positive only in 4% of the platelet-sized fragments, with a calculated true platelet count of 4 x 10(9)/1. The presence of cell fragments masquerading as platelets should be suspected in leukaemia patients with bleeding symptoms and normal or near normal platelet counts.     

Panhandle PCR: a technical advance to amplify MLL genomic translocation breakpoints

Translocations involving a breakpoint cluster region of the MLL gene at chromosome band 11q23 are the most common molecular abnormalities in acute leukemias of infants and acute leukemias related to chemotherapy with DNA topoisomerase II inhibitors. Molecular cloning of MLL genomic breakpoints by PCR has previously been difficult because MLL has many translocation partners and several breakpoints involve unknown partner genes. We review a new approach to MLL genomic breakpoint cloning called panhandle PCR. By adding an oligonucleotide sequence to the unknown 3' partner gene that is complementary to a known 5' MLL sequence, we have been able to generate a genomic template with an intrastrand loop for PCR schematically shaped like a pan with a handle. The intrastrand loop contains the translocation breakpoint and unknown partner DNA, while the handle contains the known 5' sequence from MLL and a complement to that sequence. Primers both derived from MLL are used to amplify the breakpoint by panhandle PCR. Panhandle PCR offers the advantage of having specificity for the strand of interest at both primer annealing sites without requiring specific primers for the many partner genes of MLL. Panhandle PCR is a straightforward method that represents a technical advance in MLL genomic breakpoint cloning.     

Human T lymphocyte activation in the presence of acute myelogenous leukaemia blasts: studies of allostimulated interferon-gamma secretion

Normal peripheral blood mononuclear cells (PBMC responders) were cultured together with non-irradiated allogeneic PBMC (more than 95% leukaemia blasts) derived from patients with acute leukaemia (referred to as leukaemic PBMC stimulators). Cytokine secretion was determined as cytokine concentrations in supernatants. Both normal PBMC and enriched CD4+ and CD8+ T cells responded to allostimulation with interferon (IFN gamma) secretion. Interleukin-I (IL-1) receptor antagonist and IL-2-neutralizing antibodies decreased IFN gamma secretion. Exogenous IL-1 beta, IL-2 and IL-7 increased allostimulated IFN gamma secretion, whereas decreased levels were seen in the presence of IL-6, IL-10 and granulocyte-colony-stimulating factor (G-CSF). During allorecognition IFN gamma-neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast secretion of G-CSF. We conclude that (i) both CD4+ and CD8+ T cells show allostimulated cytokine secretion in response to allogeneic stimulator cells containing a dominating population of native, cytokine-secreting leukaemia blasts, and (ii) IFN gamma released during this response can modulate the function of allogeneic AML blasts.     

In utero diagnosis of intrapericardial teratoma: a case for in utero open fetal surgery

We present a case of intrapericardial teratoma diagnosed by ultrasound at 26 weeks of gestation presenting as a large tumour mass and rapid development of hydrops fetalis. The fetus died in utero one day before scheduled open fetal surgery.     

In utero ultrasonographic diagnosis of an aberrant umbilical vein associated with fetal hepatic hyperechogenicity

Intra-hepatic abnormalities of the fetal umbilical venous system are poorly documented and clinically not well understood. A case of routine ultrasound examination at 23 weeks' gestation demonstrating foci of hepatic hyperechogenicity and cardiomegaly is presented. Colour Doppler detected absence of flow in the ductus venosus and markedly increased blood flow through an aberrant channel connecting the umbilical vein with the right atrium. The pregnancy was terminated and anomalous venous drainage of the umbilical vein into an enlarged hepatic vein was found, as well as hepatic congestion and focal hepatic necrosis and calcifications. Incidental findings of fetal hepatic hyperechogenicities require colour Doppler investigation of the intra- and extra-hepatic venous systems. We propose that a thrombo-embolic mechanism may be involved in the pathogenesis of these lesions.     

Serum LDH value as a predictor of clinical outcome in acute myelogenous leukaemia of the elderly

PURPOSE: To determine whether the diagnostic quality of computed tomography (CT) during arterial portography (CTAP) performed via the splenic artery (SA) is better than that performed via the superior mesenteric artery (SMA). MATERIALS AND METHODS: The authors evaluated CTAP images obtained in 98 patients from 1991 to 1994; 47 examinations were performed via the SA and 51 were performed via the SMA. Images were reviewed, by consensus, by three radiologists blinded to catheter location. Hepatic enhancement was quantitatively assessed in 53 patients (31 in the SA group, 22 in the SMA group). RESULTS: The numbers of low-attenuation non-tumor-related perfusion defects (19 in the SA group, 17 in the SMA group), high-attenuation non-tumor-related perfusion defects (six in the SA group, six in the SMA group), diffuse mottled perfusion abnormalities (six in the SA group, five in the SMA group), and portal venous flow defects (20 in the SA group, 20 in the SMA group) were similar in both groups (P > .05). Peak hepatic enhancement was similar in both groups (SMA group = 111 HU; SA group = 112 HU) (P > .05). CONCLUSION: There is no difference in quality between CTAP performed via the SA versus CTAP performed via the SMA.     

Hemoperitoneum due to splenic rupture in a CAPD patient with chronic myelogenous leukemia

BACKGROUND: Due to the expression of urease, Helicobacter pylori is able to establish itself in the human stomach under acidic conditions. A novel host defence mechanism was recently proposed, suggesting that the formation of salivary nitrite in symbiosis with facultative anaerobic bacteria in the oropharynx, is aimed at enhancing the antimicrobial activity of gastric juice. AIMS: To investigate whether the addition of nitrite in physiological concentrations influences the resistance of H pylori to acid. METHODS: H pylori cultured from fresh gastric Biopsy specimens was exposed for 30 minutes to normal saline and to HCl/KCl buffer (0.2M) at pH 2 with urea (5 mM) added. The influence of potassium nitrite (50-1000 mumol/l) on bacterial survival was determined. RESULTS: Addition of nitrite (1 mM) to acidic solutions (pH 2) resulted in complete kill of H pylori within 30 minutes exposure time whereas acid alone allowed the organism to survive (p < 0.001). The antimicrobial effect of nitrite at pH 2 against H pylori was dose dependent and complete kill of organisms occurred at concentrations > or = 500 mumol/l. CONCLUSION: Acidified nitrite has anti-bacterial activity against H pylori. This should prompt further research into the effect of salivary nitrite on the survival of H pylori in the human stomach.     

Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression

Ewes actively immunized against alpha N, the N-terminal peptide of inhibin alpha 43 precursor, have lowered fertility associated with ovulation failure, restricted tissue remodelling and reduced matrix metalloproteinase-2 activity in the follicular fluid at the time of expected ovulation. This could be due to altered ratios of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase (TIMP-1), or to the onset of atresia in antral follicles destined to ovulate. The objectives of the present study were to investigate the effects of immunization against alpha N on the localization of TIMP-1 in ovine follicles, and on follicular growth and atresia in the follicular phase. Ewes were either immunized against alpha N or remained as controls and the ovaries were removed before (0, n = 4) and at 12 h (n = 4) and 24 h (n = 4) after hCG administration in a synchronized follicular phase, 48 h after removal of intravaginal pessaries. Observations were made on a single section taken through the largest follicle present in the ovaries of each ewe. There were no healthy antral follicles > 1 mm in immunized ovaries (0/29) compared with controls (16/31) (P < 0.001), whereas the proportion of healthy antral follicles < 1 mm was the same in each group (9/19 versus 5/12). TIMP-1 immunoactivity was localized in large luteal cells, smooth muscle and endothelial cells, and in all antral follicles, including oocytes. At the time of hCG administration, no TIMP-1 immunoreactivity was detected in the apical region of the follicular wall of large follicles (> 6 mm) compared with the rest of the follicle wall, but staining appeared in the apical granulosa layer 24 h later. In newly formed corpora lutea, TIMP-1 expression was found along the invaginating vascular layer. There was no effect of immunization on the patterns of TIMP-1 immunoreactivity, suggesting that changes in TIMP-1 are not involved in the effects of alpha N. These data are consistent with a paracrine role for alpha N in the selection and atresia of antral follicles, and for TIMP-1 in tissue reorganization and steroidogenesis at the time of ovulation.     

In utero fetal death in multiple pregnancies during the second and third trimesters. A series of 21 cases

OBJECTIVE: Recall the maternal and fetal risks in multiple pregnancies with in utero death during the second and third trimester. METHODS: From january 1, 1984 through December 31, 1994 21 cases of in utero death occurred among 405 multiple pregnancies followed in our unit. The frequency and circumstances of maternal and fetal complications were established according to type of placenta implantation, etiology, term at death of the twin and delay from death to delivery. RESULTS: The rate of in utero death was 5.2%. Various etiologies were observed, but the main cause was intra-uterine growth retardation. Maternal complications were marked by moderate asymptomatic disorders in hemostasis which resolved rapidly. Fetal complications included premature delivery (20/25 infants) and multicystic encephalopathy in one surviving twin. In monochorial pregnancies there is either tromboplastin release or hypotension-hypoxia phenomena which lead to neurological lesions. CONCLUSION: Fetal prognosis depends essentially on the type of placenta implantation. The most severe fetal complications are caused by neurological damage occurring in monochorial pregnancies. Screening for this anomaly is difficult, limiting the antenatal evaluation to the prognosis of the surviving twin. In bichorial pregnancies, and even more so in monochorial pregnancies. It is important to prevent premature delivery and maintain regular obstetrical care. The ultrasound-Doppler examination is the key to follow-up in pregnancy.     

Fetal enterolithiasis and anhydramnios; due to in utero hepatorenal syndrome?

Enterolithiasis is a rare, prenatal ultrasonographic finding. Previously reported cases were invariably associated with major fetal malformations. We describe a case of fetal enterolithiasis and anhydramnios in an anatomically normal fetus who, at autopsy, showed end-stage fetal liver disease. Fetal hepatorenal syndrome is the most probable cause of this in utero sonographic combination.     

Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.     

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.     

Sudden death due to recuperated ventricular fibrillation: Brugada syndrome?

We report a 47 years old male who was recuperated from a sudden death, and in whom the cardiological assessment showed a right bundle branch block and a fluctuating ST segment elevation V1 to V3. During the electrophysiological study, a polymorphic tachycardia and a ventricular fibrillation were induced. Procainamide administration enhanced ST segment alterations in right precordial leads, and isoproterenol normalized the EKG. All these disturbances are similar to the condition described by Brugada brothers. The patient was treated with an internal implantable defibrillator, without the use of antiarrhythmic drugs and is well after four months of follow up.     

Mitoxantrone in the treatment of acute myelogenous leukemia: a review

Mitoxantrone is an intravenous anthracenedione structurally related to the anthracycline antibiotics. This drug has been used for several years in the treatment of acute myelogenous leukemia (AML). Its use has been based on its pharmacological properties, its incomplete cross-resistance with other intercalating agents, and its better tolerance as predicted by preclinical studies. Various treatment schedules, using mitoxantrone alone and in combination with other antileukemic agents, have been used in clinical trials. Complete remission (CR) rates ranged from 14 to 44% in refractory AML and from 46 to 79% in relapsed patients. Although a superiority of mitoxantrone over anthracyclines has not been clearly demonstrated in newly diagnosed patients, mitoxantrone is now recognized as a useful drug in first line therapy. The tolerability profile of mitoxantrone indicates that it offers patients an acceptable quality of life compared with standard treatment regimens, and could be a good alternative to the anthracyclines. The development of new therapeutic concepts aiming at an optimization of its use is now in process and first results are promising.