Human herpesvirus-6 (HHV-6): current status

Bacteria isolated from the urine of 142 patients with chronic pyelonephritis (CPN) were examined for pathogenic properties of the strains (bacteriuria, hemolytic, proteolytic properties, urease, adhesive activity, antibiotic resistance, the ability to inactivate bactericidal activity of the serum) to control the effect of the treatment: antibiotics combined with plasmapheresis or antibiotics combined with laser radiation (intravascular, transcutaneous, or both). Combined application of intravascular and transcutaneous laser irradiation in multimodality treatment reduces the number of highly pathogenic strains as well as antibactericidal activity of the urine strains. It also promotes normalization of bacteriuria level. Plasmapheresis is inferior to laser radiation but ranks the second in efficacy of action on urinary microflora. Thus, use of efferent methods, especially transcutaneous plus intravascular laser radiation, plasmapheresis, in combined treatment of pyelonephritis decreases pathogenicity of urine strains and normalizes bacteriuria.     

Results of the double stapling procedure in colorectal surgery

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprung's disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprung's disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprung's disease.     

Acute renal failure in pregnancy

Between 1982 and 1992, 18 cases of pregnancy-related acute renal failure (PR-ARF) were observed (9% of the total number of ARF). Mean age of the women was 32 years (22-40 years). Uterine hemorrhage and preeclampsia/eclampsia were the major causes of ARF, accounting for 61% of the cases. Patchy renal cortical necrosis was suspected in 2 cases whereas signs of disseminated intravascular coagulation (DIC) or microangiopathic hemolytic anemia were present in 6 (33%) and 9 (50%) cases, respectively. Ten women required hemodialysis; and 6 of them, additional plasma exchange sessions. Five patients (28%) died during the acute phase of the illness, mainly due to brain damage, hepatic failure, and sepsis. Among the survivors, a complete (61.5%) or partial recovery (23.1%) was usually seen, but irreversible renal failure was recorded in 2 cases with postpartum hemolytic uremic syndrome (HUS). Short-lasting oligoanuria (< 3 days) represents a good prognostic index. However, the presence of vascular injury (cortical necrosis, HUS) seems to carry a poor prognosis. In conclusion, PR-ARF is still a critical occurrence, associated with serious prognosis for both women and kidneys. So far, the most effective measures remain the careful prevention and the aggressive management of the obstetric complications.     

Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts

BACKGROUND: Intravascular fibrin deposition and platelet sequestration occur with porcine xenograft rejection by baboons. Disseminated intravascular coagulopathy may arise either as a direct consequence of the failure to fully deplete xenoreactive natural antibodies and block complement, or because of putative cross-species molecular incompatibilities in this discordant species combination. METHODS: Three baboons were conditioned with retrovirally transduced autologous bone marrow to induce tolerance to swine antigens. Xenoreactive natural antibodies and complement were depleted by plasmapheresis and the use of Gal alpha1-3Gal column adsorptions; baboons were then splenectomized and underwent renal xenografting from inbred, miniature pigs. Soluble complement receptor type-1 with protocol immunosuppression (mycophenolate mofetil, 15-deoxyspergualin, steroids, and cyclosporine) was administered. RESULTS: A bleeding diathesis was clinically evident from days 5 to 12 after transplantation in two baboons. Low levels of circulating C3a, C3d, and iC3b were measured despite the absence of functional circulating complement components. Profound thrombocytopenia with abnormalities in keeping with disseminated intravascular coagulopathy were observed. Prolongation of prothrombin and partial thromboplastin times was accompanied by evidence for tissue factor-mediated coagulation pathways, high levels of thrombin generation (prothrombin fragment F(1+2) production and thrombin-antithrombin complex formation), fibrinogen depletion, and production of high levels of the fibrin degradation product D-dimer. Importantly, these disturbances resolved rapidly after the excision of the rejected xenografts in two surviving animals. Histopathological examination of the rejected xenografts confirmed vascular injury, fibrin deposition, platelet deposition, and localized complement activation. CONCLUSIONS: Systemic coagulation disturbances are associated with delayed xenograft rejection.     

Severe and fatal mass attacks by 'killer' bees (Africanized honey bees--Apis mellifera scutellata) in Brazil: clinicopathological studies with measurement of serum venom concentrations

In S?o Paulo State, Brazil, five males, aged between 8 and 64 years, were attacked by 'Africanized' honey bees (Apis mellifera scutellata). The estimated number of stings received by each patient ranged from > 200 to > 1000. All five were transferred to intensive care units in S?o Paulo City. Clinical features included intravascular haemolysis, respiratory distress with ARDS, hepatic dysfunction, rhabdomyolysis (with myoglobinaemia and myoglobinuria), hypertension and myocardial damage (perhaps explained by release of endogenous catecholamines by venom phospholipase A2 and mellitin), shock, coma, acute renal failure and bleeding. Laboratory findings included gross neutrophil leucocytosis, elevated serum enzymes [AST, ALT, LDH, CPK (predominantly CPK-MM)] and creatinine. Clotting times were slightly prolonged. Despite treatment with antihistamines, corticosteroids, bronchodilators, vasodilators, bicarbonate, mannitol and mechanical ventilation, three of the patients died between 22 and 71 h after the attacks, with histopathological features of ARDS, hepatocellular necrosis, acute tubular necrosis, focal subendocardial necrosis and disseminated intravascular coagulation. Whole bee venom and phospholipase A2 (PLA2) antigen concentrations were measured in serum and urine for the first time, using enzyme immunoassay. High venom and PLA2 concentrations were detected in serum and urine for more than 50 h after the stings in two fatal cases, in one of which the total circulating unbound whole venom was estimated at 27 mg, one hour after the attack. An antivenom should be developed to treat the increasing numbers of victims of mass attacks by Africanized 'killer' bees in USA, Middle and South America.     

Microwave coagulation therapy for hepatocellular carcinoma

BACKGROUND & AIMS: Surgical resection is not always feasible in patients with hepatocellular carcinoma. Microwave coagulation therapy has been used as an alternative to resection, and its efficacy has been evaluated. METHODS: Nineteen patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy through laparotomy (n = 12), laparoscopy (n = 5), or thoracotomy (n = 2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 13 patients, tumor size ranged from 5 to 90 mm. Patient outcomes were studied. RESULTS: Microwave coagulation therapy created a reproducible regional necrosis. Fourteen patients underwent potentially curative treatment; the remaining 5 patients underwent palliative treatment (n = 4) or incomplete tumor coagulation (n = 1). Of the 31 nodules treated, 28 underwent complete tumor ablation. Only 2 patients undergoing laparoscopic microwave coagulation therapy developed local recurrence. The coagulated area subsequently shrank. Patients showed rapid recovery without hepatic dysfunction. Thirteen patients, including 2 long-term survivors, are alive either without tumor (n = 10; 14-64 months) or with tumor (n = 3; 17-22 months). Six patients died of hepatocellular carcinoma (n = 4) or liver insufficiency (n = 2). CONCLUSIONS: This preliminary study suggests the efficacy of microwave coagulation therapy, including safety and potential curability, in patients with hepatocellular carcinoma with advanced liver cirrhosis and multifocal or central tumors.     

Purpura fulminans in the newborn. Report of two cases successfully treated with heparin and antithrombin III

Purpura fulminans is a rare form of disseminated intravascular coagulation characterized by rapidly progressive purpuric lesions, hypotension and, in some cases, fever. In neonates, purpura fulminans usually develops following deficiency of anticoagulant protein C or S, although acquired forms have been described. The management of disseminated intravascular coagulation is still controversial, with some studies finding a positive effect of anticoagulants and others showing no effect or even a detrimental one. Therefore, at present, management is limited to the treatment of underlying disease and replacement of clotting factors. Personal experience is reported on the efficacy of heparin in combination with antithrombin III in the treatment of purpura fulminans in two preterm neonates who did not have inherited deficiency of protein C or S and developed the disease possibly following prolonged labor (36 hours) in the first case, and maternal neoplasia, in the second. Both neonates presented with widespread cyanotic areas rapidly evolving in purpuric lesions and hemorrhagic bullae. Laboratory tests (prolonged prothrombin and partial thromboplastin time, fibrinogen and antithrombin III concentrations below normal ranges, d-dimer highly positive) were consistent with disseminated intravascular coagulation. In both cases anticoagulant treatment with heparin (50 UI/kg in bolus followed by 15 UI/kg/h) and antithrombin III was associated with resolution of disseminated intravascular coagulation and prompt amelioration of the purpuric lesions, without apparent side effects.     

Interactions of mitochondrial ATP synthesis and the creatine kinase equilibrium in skeletal muscle

This study aimed to evaluate the effect of FR128998, (1s,6s)-1-benzyl-10-(3-pyridyl-methyl)-7-thia-10-azaspiro [5,6]-dodecan-11-one 7,7-dioxide hydrochloride, a novel platelet activating factor (PAF) receptor antagonist, on endotoxin lipopolysaccharide-induced disseminated intravascular coagulation in rats. Experimental disseminated intravascular coagulation was induced by an infusion of lipopolysaccharide at 0.25 mg/kg/h for 4 h. Simultaneous infusion of FR128998 (0.25 and 1.0 mg/kg/h) with lipopolysaccharide dose dependently inhibited thrombocytopenia, but not leukopenia. The changes in coagulation parameters of disseminated intravascular coagulation, i.e., prolongation of activated partial thromboplastin time and elevated levels of fibrinogen/fibrin degradation products, were also prevented by the treatment with FR128998. In addition, FR128998 attenuated the increase in serum tumor necrosis factor (TNF) which appeared during the initial stage of disseminated intravascular coagulation. FR128998 (10 microM) also inhibited the TNF production by peripheral blood leukocytes or alveolar macrophages stimulated by lipopolysaccharide in vitro. Furthermore, TNF production induced by PAF itself in vitro was also inhibited in the presence of FR128998. These data indicate that PAF plays a pivotal role in the development of disseminated intravascular coagulation via TNF production.     

Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer

BACKGROUND: No useful predictor of resistance or sensitivity to second-line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S-transferase-pi (GST-pi) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemotherapy. METHODS: Tumor samples were obtained from 26 patients with relapsed epithelial ovarian cancer 3-4 weeks before the initiation of second-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-pi in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. RESULTS: The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7%) significantly exceeded that for the nonresponders (9.1%). Expression of GST-pi by immunohistochemical staining was more frequently observed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). Western blot analysis detected GST-pi in all cases. There was no significant difference in the relative density values of the GST-pi Western blot analysis between the two groups. The mean value of GSH concentration in nonresponders was significantly higher than in responders (18.4 +/- 9.7 vs. 7.5 +/- 8.2 microg/mg protein). GSH concentration was below the cutoff point (10.3 microg/mg protein) in all responders except one. CONCLUSIONS: Second-line chemotherapy consisting of etoposide and cisplatin is effective in the treatment of relapsed epithelial ovarian cancer. In addition, tumor concentration of GSH may be a useful predictor of the response to this therapy.     

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock

OBJECTIVES: To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS: We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.     

Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas

A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.     

Stroke in the medical intensive-care unit

OBJECTIVE: To analyze the occurrence and outcome of new-onset stroke in critically ill patients admitted to a medical intensive-care unit. MATERIAL AND METHODS: We reviewed the medical records of patients admitted to the medical intensive-care units of two hospitals between 1985 and 1995. In addition, computed tomographic scans or scan reports were assessed. RESULTS: We identified 19 patients with a critical medical illness and a new-onset stroke. Of this study group, ischemic stroke developed in 10 patients, 8 of whom were found to have bihemispheric infarction. A single territory infarct (the middle cerebral artery territory) was noted in two patients. The presumed mechanisms for ischemic stroke were disseminated intravascular coagulation (N = 6), cholesterol embolization (N = 1), discontinuation of warfarin therapy before an invasive procedure (N = 1), septic emboli (N = 1), and cardioversion (N = 1). In nine patients, an intracranial hemorrhage developed. Seven patients had a single lobar hematoma, whereas multiple intracerebral hematomas were found in two patients. Disseminated intravascular coagulation and rupture of a mycotic aneurysm in proven infective endocarditis were the most common mechanisms for hemorrhagic stroke. In all patients with an ischemic stroke, sudden hemiparesis rapidly progressed to coma. In patients with an intracranial hematoma and sudden onset of coma, unilateral fixed pupil was the most common initial manifestation. Of the 19 patients, 17 died and 2 remained severely disabled. CONCLUSION: Coma is a common initial manifestation of stroke in patients with a critical medical illness, and disseminated intravascular coagulation has a major etiologic role. New-onset stroke in the setting of critical medical illness generally is a complication in a terminally ill patient.     

Renal hematoma after shockwave extracorporeal lithotripsy

OBJECTIVE: Renal haematomas after shock wave extracorporeal lithotripsy (SWEL) represent a potentially serious complication. This paper examines those cases of post-SWEL renal haematoma seen in our Centre, analyzing the likely risk factors. PATIENTS AND METHODS: Between May 1988 and June 1996, 12,800 patients were treated with 15100 lithiasis at some level of the urinary tract requiring 16,000 SWEL sessions. All treatments were done with a Dornier HM-4 lithotripter. Voltage applied ranged from 18 to 26 Kv, averaging 2500 waves/session. Complementary testing (ultrasound/computerised tomography) was requested immediately after treatment if clinical complications were suspected. RESULTS: A total of 10 renal haematomas (0.078%) were diagnosed. Six cases were mild, but 4 presented extensive haematoma with significant haemodynamic consequence. Although in one case nephrectomy was undertaken to control haemorrhage, death finally occurred by disseminated intravascular coagulation. Four patients who developed haematoma were hypertensive and 3 had a previously corrected haemostasis alteration. CONCLUSIONS: The possibility of renal haematoma should be taken into account in the face of persistent and unjustified pain after SWEL treatment. Normalization of blood pressure values, correction of urinary infection as well as adequate correction of haemostatic disorders is advisable.     

Morphological and functional aspects of the cardiovascular system related to aging: does "aging heart" exist?

Thromboembolic disease (TE) is an important cause of in-hospital morbidity and mortality. The relationship between cancer and abnormalities of blood coagulation has been recognized for well over a century. Deep venous thrombosis (DVT) of the lower extremities is the most common cause of thromboembolic disease, but pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular coagulation, and other, more unusual, clinical events, may occur. Unexplained TE may serve as a marker for the presence of a hidden tumor. The frequency of pulmonary embolism (PE) among patients with a malignant neoplasm at necropsy is highly increased in the elderly patients. Among subjects with a malignant neoplasm, patients with pancreatic and gastric cancer (mucin-secreting adenocarcinomas), cancer of the large bowel and women with ovarian cancer had the highest frequency of PE. Old age, female sex, gastrointestinal and ovarian cancers must be considered as a significant risk factor for PE. The potentially responsible mechanisms for the thrombotic events, clinical manifestations, diagnostic implications and aspects of treatment of TE in malignant disease are discussed.     

Effects of gestation age and of birth weight in the concentration of carnitine in the umbilical plasma

36 patients with relapsed (29) or refractory (7) acute lymphoblastic or nonlymphoblastic leukaemia received regimens employing 1-3 courses of mitoxantrone (or idarubicin), intermediate doses of cytarabine and etoposide. Complete remission (CR) was achieved in 30% of patients (5/15 ALL, 6/21 AML, 5 cases of refractory and 6 of relapsed leukaemia). Duration of CR was 3-6+ months (3 patients are still alive). Toxicity of the treatment was acceptable, however 5 patients with severe granulocytopenia died from sepsis.     

Coagulation and vascular abnormalities in Crow-Fukase syndrome

Coagulation and vascular abnormalities were studied in 4 patients with Crow-Fukase syndrome (CFS or POEMS) to understand the pathophysiology. Fibrinogen, fibrinopeptide A, and thrombin-antithrombin complexes (TAT) increased in sera during active phase of CFS. In nerves of 2 untreated cases, the endothelium of small vessels was immunohistochemically stained with antithrombin III antibody, which indicates the existence of TAT. HLA-DR+ inflammatory cell infiltrate surrounded these vessels. Blood-nerve barrier opening was suggested by strong immunoglobulin staining in the endoneurium. More than 50% of endoneurial blood vessels had narrowed or closed lumina with thick basement membranes. Endothelial cell abnormality and chronic intravascular coagulation may play an important role in the pathogenesis of CFS, in addition to a still unknown demyelinating factor. Refractory cases responded to combined treatment of prednisolone, human leukocyte interferon, and antithrombin drug.     

Staging of breast cancer: what standards should be used in research and clinical practice?

BACKGROUND: Bone scan (BS), chest X-rays (CXR), liver ultrasonography (LUS) and laboratory parameters (LP) are frequently used as routine staging procedures for breast cancer patients. These procedures are not always appropriate in either clinical or research settings, regardless of the stage. The aim of this study was to identify groups of patients with differing risks for metastases in order to select more precise standard staging procedures. PATIENTS AND METHODS: The staging data relating to 406 breast cancer patients consecutively referred to our institution between November 1989 and October 1996 were analysed including pathological TNN grading and biological parameters. All of the cases with a positive or suspicious pre-operatory staging and who proved to have metastatic disease before surgery or during the first six months of follow-up were considered true-positive; all of the other cases with a positive or suspicious initial staging but with no evidence of distant metastasis before surgery and with a disease-free survival longer then six months were considered false-positive. In the same way all cases with negative initial staging who relapsed during the first six months of follow-up were considered false-negative and those with negative initial staging and with a disease-free survival longer then six months were considered true-negative. Statistical analysis was performed using Fisher's exact test. RESULTS: BS, CXR and LUS, 388, 399 and 398 examinations respectively, were considered available, and 17 (4.38%), six (1.5%) and four (1%), respectively, proved to be true-positive. A statistically significant difference was observed when our cases were grouped according to T status (T4 vs. T1-T2-T3, P < 0.01) and nodal status (N0-N1 cases with less than three involved nodes and N1 with more than three positive lymph nodes N2 patients, P < 0.01). CONCLUSIONS: The present study suggests that breast cancer patients can be divided into three subgroups with different detection rates for distant metastases at staging (0.59%, 2.94% and 15.53%), and that the standard practice should be changed. In the first (T1N0 and T1N1 patients with < or = 3 positive lymph nodes--41.13% of the patients) and the second group (T2N0, T2N1 with < or = 3 positive lymph nodes, T3N0 and T3N1 patients with < or = 3 positive lymph nodes--33.49% of the patients) there is no need for a complete set of staging procedures, whereas full procedural staging is needed in the third group of patients (T4, N1 with > 3 lymph nodes and N2, 25.37% of the patients).     

Valproic acid overdose and L-carnitine therapy

We examined the primary ischaemic changes in the pancreas in 35 patients with disseminated intravascular coagulation. In 7 (20%), multiple patchy lesions composed of degenerative acinar cells indicating coagulation necrosis were noted. None of these lesions was accompanied by fat necrosis. The patchy lesions involved the islets of Langerhans in only 1 case. The interlobular arteries of the pancreas near these lesions contained fibrin thrombi in all 7 cases. We suggest that these lesions, without fat necrosis, are the distinctive ischaemic change associated with disseminated intravascular coagulation.     

Soluble L-selectin increases in the cerebrospinal fluid prior to meningeal involvement in children with acute lymphoblastic leukemia

We have treated 19 B-chronic lymphocytic leukaemia (B-CLL) patients with CDA (Leustat, Janssen-Cilag). Four patients developed severe autoimmune haemolytic anaemia, and 2 of these had severe reticulocytopenia due to red cell aplasia/hypoplasia. Two patients died as a complication of the haemolysis one during the primary episode, with a clinical course suggestive of transfusion associated graft-versus-host disease (taGVHD), and one following a relapse of haemolysis. The onset of haemolysis occurs within 4 cycles of CDA therapy and is temporally related to the T-lymphocyte nadir induced by CDA. The presence of a positive DAT prior to therapy in 3 of 4 patients developing haemolysis suggests that the CDA induced T-lymphocytopenia may exacerbate the tendency of certain CLL patients to autoimmune haemolysis.     

Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukaemia

Seven relapsed and/or refractory acute promyelocytic leukaemia patients were treated by arsenic trioxide (As2O3). Four patients (4/7, 57%) achieved complete remission after one to three cycles of treatment and the most common acute side-effect was fluid retention (in six patients, 86%), including weight gains and pleuro-pericardial effusions. Evident polyneuropathy compatible with chronic arsenic toxicity was noted in two of the three patients who received As2O3 maintenance therapy and one of them had marked distal muscular atrophy. We suggest that As2O3 may be a useful salvage therapy for relapsed and refractory APL patients, but the acute or chronic arsenic toxicity should be carefully monitored.