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Journal URL: http://bloodjournal.hematologylibrary.org/

Familial Mediterranean fever (FMF) is a heterogeneous disorder; at present, it is diagnosed using only genetic methods. In the current study, we performed molecular analysis in two families presenting with FMF. In the first family, we report two brothers with a common genotype (M694V/V726A) but with different clinical presentation. In the second family, we identified the M694V and K695R mutations in a presymptomatic carrier. © Copyright 2008, Mary Ann Liebert, Inc.

A hexadecyltrimethylammonium bromide (CTAB) method for isolating fungal DNA from clinical samples, suitable for PCR amplification is described. Yeast and filamentous fungi DNA from clinical samples was amplified with primers complementary to the genes coding for rRNA, amplifying a 105 bp fragment and internal transcribed spacer primers amplifying fragments between 242 and 622 bp. The level of sensitivity was 10 ± 5 yeast and 28 Aspergillus fumigatus CFU ml-1 of biological fluid.

The in vitro and in vivo efficacy of roxithromycin was compared with that of erythromycin, against a methicillin-susceptible strain of Staphylococcus epidermidis. We performed standard in vitro testing (MIC, MBC, and time-kill kinetics) for roxithromycin, erythromycin, and rifampin. Both macrolides were bacteriostatic in vitro. There was no significant difference in microbial survival between erythromycin and roxithromycin groups in the time-kill kinetics (p = 0.3). For the in vivo experiments, using the rabbit experimental endocarditis model, roxithromycin was found to be inferior to erythromycin in decreasing the microbial burden of the endocardial vegetations (p < 0.05). Rifampin was highly effective, both in vitro and in vivo. In conclusion, the efficacy of roxithromycin was poor and inferior to erythromycin against a strain of methicillin-susceptible S. epidermidis. (C) 1998 Elsevier Science Inc.

The function of the hypothalamic-pituitary-adrenal axis as related to the degree of severity of a septic process was assessed by measuring plasma levels of beta-endorphin, ACTH and cortisol. Sixty-one cases of postoperative patients treated at the intensive care unit were classified into four groups according to the severity of infection: Group 1 (control) included patients who did not show any sign of infection, group 2 patients with sepsis, group 3 patients with septic syndrome and group 4 patients with septic shock. Compared to G1 patients’ ACTH values (4.16+/-2.6 pg/ml), a statistically significant increase in ACTH values in various stages of septicemia (p < 0.005) with a noticeable difference also between G3 (7.11 +/- 3.7 pg/ml) and G4 (11.5 +/- 6.6 pg/ml) (p

We present two cases of biopsy proven tuberculosis of the pancreas in non-immunocompromised patients diagnosed and treated in our unit within the last 14 years, The first case presented with abdominal pain and fever, and the second with iron deficiency anaemia and severe weight loss. In both cases abdominal ultrasound and computed tomography suggested a pancreatic carcinoma. There was no pulmonary or intestinal tuberculosis. The tuberculin skin test was positive. Upon exploratory laparotomy the macroscopic appearance of the pancreas was that of an inoperable pancreatic carcinoma. Following the histological diagnosis of pancreatic tuberculosis, both patients were successfully treated with triple antituberculous therapy for 6 months, Isolated pancreatic tuberculosis is an extremely rare disease with only 41 cases in non-immunocompromised patients reported worldwide (1966-1997), It is a curable disease and should be considered in the differential diagnosis of a pancreatic mass or abscess shown on ultrasound or computed tomography, especially in developing countries, where tuberculosis is common. Eur J Gastroenterol Hepatol 10:973-976 (C) 1998 Lippincott Williams & Wilkins.

To determine the prevalence of activated ras-oncogenes (N-ras, Harvey-ras Kirsten-ras), DNA derived from peripheral blood of 51 patients with myelodysplastic syndrome (MDS) was investigated, The method was based on the polymerase chain reaction (PCR) technique to amplify DNA, followed by restriction fragment length polymorphism (RFLP) analysis, Among the French-American-British (FAB) subtypes, N-ras mutations were found in two patients with refractory anemia with excess of blasts (RAEB), in one patient with refractory anemia with excess of blasts in transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter survival duration than other MDS patients of the same FAB subtypes, although these findings proved to be not statistically significant (P > 0.1). Interestingly, all but one patient with N-ras mutation developed acute myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12 of the N-ras gene might serve as a negative prognostic factor at diagnosis of MDS.

Objective: To evaluate and compare in vivo the protective efficacy of unilamellar liposomal amphotericin B (L-AmB) with that of deoxycholate amphotericin B (D-AmB) in experimental endocarditis, Material and Methods: In the rabbit model of experimental Aspergillus fumigatus endocarditis, Ino doses of each antifungal agent (1.5 mg/kg each) were administered intravenously at 4 hours and at 30 minutes before challenge with an inoculum of A. fumigatus. Three days later, the animals were sacrificed, and the aortic vegetations were analyzed, Results: All 19 animals that did not receive chemoprophylaxis acquired endocarditis, In contrast, endocarditis developed in 2 of 10 animals pretreated with D-AmB (P

delta-Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured delta-aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [($) over bar x (SD)] did not differ between groups A and B [0.51 (0.21) and 0.43 (0.19) mu mol L(-1), respectively] while those of group C [2.28 (0.56) mu mol L(-1) were significantly higher (P < 0.001) as compared to the controls. delta-Aminolaevulinic acid dehydratase activity [($) over bar x (SD)] was significantly increased [3599 (1909) mu mol L(-1) h(-1)] in group B and decreased in group C [1052 (532) mu mol L(-1) h(-1)] as compared to the controls [2034 (446) mu mol L(-1) h(-1)] (P < 0.001). There was a significantly negative correlation of logarithm of delta-aminolaevulinic acid dehydratase with lead in both groups B (P < 0.05) and C (P < 0.001) but not in group A (P = 0.1). delta-Amino-laevulinic acid dehydratase activity had a high specificity (100%) but a low sensitivity (37%) as an index of toxic lead exposure. According to our data the value of delta-aminolaevulinic acid dehydratase measurement in the diagnosis of lead intoxication is doubtful in cases with low blood lead levels, while in the presence of iron deficiency its reliability is further reduced, since low blood lead levels may be falsely predicted. delta-Aminolaevulinic acid dehydratase activity should be restricted only to monitoring cases with moderate or severe lead poisoning.

The purpose of the present study was to evaluate patients with the antiphospholipid syndrome with particular attention to their initial clinical features, final diagnoses and the course of thrombotic events in association with therapy. The methodology applied was the following: retrospective analysis of 30 patient files (20 female, 10 male) with antiphospholipid syndrome (APS). Four types of therapy were evaluated for their efficacy to prevent thrombotic recurrences, aspirin 100 mg daily plus low-dose prednisone 10-15 mg daily, warfarin (with international normalized ratio 2 to 2.6), immunotherapy alone and no therapy. None of the patients was followed-up during pregnancy. The probability of thrombosis-free survival was estimated according to Kaplan-Meier method, while the statistical significance was tested by the log rank test. There were 21 patients with primary APS and 9 with secondary, 8 of whom had SLE and one patient who had primary Sjogren’s syndrome. The age at onset and the disease duration did not differ between men and women, while patients with secondary APS had a longer disease duration than patients with primary APS, a finding indicating that SLE patients develop, for unknown reasons, APS a long time after the initiation of their disease. Twenty patients experienced recurrent thrombotic events (a total of 46 recurrences) of which 43 (93%) were identical to the first event. Thus, in the majority of the cases arterial were followed by arterial and venous by venous thrombotic events: a finding suggesting a tissue-related factor for initiation of thromboses. Total follow-up of the patients was 154 patient years, of which 98 patient years were after the first thrombotic episode. More specifically: aspirin plus low-dose prednisone, 38 patient years; warfarin therapy, 15; immunotherapy alone, 10; no therapy, 35. The recurrence rates of thrombotic events were 0.13, 0.20, 0.70 and 0.88, respectively. The thrombosis-free survival after the first thrombotic event was significantly longer with aspirin plus low-dose of prednisone and warfarin therapy than with no therapy (P < 0.005 and P < 0.05, respectively). Immunotherapy alone did not prolong significantly the thrombosis-free survival compared with no therapy. Prospective studies are necessary to identify the optimum type and duration of therapy. Although immunotherapy and warfarin therapy cannot be definitely tested due to the small number of patients, the short follow-up and in the case of warfarin the low intensity of therapy, our data suggests that aspirin with low doses of prednisone and warfarin seem to be the most effective anti-thrombotic therapies in APS.

In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM‐CSF (3 μg/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14‐d periods, interrupted by 14‐d rest periods. Eight patients discontinued the treatment. In the GM‐CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM‐CSF plus AraC group but in none of the GM‐CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM‐CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3‐month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM‐CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM‐CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM‐CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases. © Munksgaard 1992

The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed.

Globin chain synthesis was studied in the reticulocytes of 30 patients with various myelodysplastic syndromes (MDS) to determine the alpha:beta globin chain synthetic ratio and its probable prognostic value. The mean (SD) value of the total alpha:beta ratio was 0.82 (0.45) ranging from 0.05 to 1.73. The same ratio in 10 normal controls was 1.01 (0.04). This difference was significant. Furthermore, the alpha:beta ratios were lower than normal in 14 patients (alpha-thalassaemia-like) (group I), almost within normal limits in 11 (group II), and higher than normal in five (beta-thalassaemia-like) (group III). In each group almost all the FAB subtypes were represented. The addition of exogenous haem in several of the test samples resulted in a slight to pronounced increase in the alpha:beta ratios, particularly in group I. In 92% of the high risk cases (refractory anaemia with excess blasts (RAEB), chronic myelomonocytic leukaemia (CMML)) or 87.5% of patients who finally developed acute non-lyphoid leukaemia (ANLL) low or normal alpha:beta ratios were found. No significant correlation was noticed between alpha:beta ratios and various haematological variables or survival. It is concluded that in MDS the alpha:beta ratio varied enormously across the entire population of patients, as well as within each FAB subtype, thereby restricting its prognostic value. Although haem deficiency may be implicated in some cases of MDS, why this should be remains unclear.

Some parameters of haem synthesis were estimated in 60 uraemic patients (30 nondialysed, 30 dialysed) and in 30 matched controls. Serum δ‐aminolaevulinic acid and erythrocyte coproporphyrin and protoprophyrin were found significantly higher in the non‐dialysed uraemics than in the controls. Erythrocyte δ‐aminolaevulinic acid dehydrase (ALA‐D) activity was 498 ± 174 μmol/h.l in the non‐dialysed patients, 321 ± 146 in the dialysed (just before haemodialysis) and 833 ± 281 in the healthy controls, the differences between these groups all being statistically significant (p < 0,001). After haemodialysis the enzymic activity in the dialysed group increased significantly (380 ± 167, p < 0.001), but remained lower than normal (p < 0,001). A similar pattern ‐ although with less statistical significance of the differences between groups ‐was observed concerning erythrocyte uroporphyrinogen I synthase activity. Incubation of normal erythrocytes with uraemic plasma resulted in a considerable decrease of their ALA‐D activity (from 830 ± 263 to 616 ± 126) while incubation of uraemic erythrocytes with normal plasma increased their ALA‐D (from 384 ± 139 to 494 ± 77). Addition of zinc in the haemolysate caused a similar induction of ALA‐D in both controls and uraemics. The zinc‐induced uraemic ALA‐D practically reached normal levels. The mechanism of enzymic depression and the possible role of elevated δ‐aminolaevulinic acid concentrations (to which depressed ALA‐D activity considerably contributes) in the pathogenesis of the neurologic manifestations of uraemia, are discussed. © Munksgaard 1986

The possible effect of cisplatin on porphyrin metabolism was studied in 25 patients with various malignancies treated with high-dose cis-diamminedichloroplatinum. Haematocrit, red blood cells, haemoglobin, white blood cells, platelets and reticulocytes together with coproporphyrin and protoporphyrin in red blood cells were determined before each course of chemotherapy in all patients. In addition, coproporphyrin, uroporphyrin, δ-aminolevulinic acid, and porphobilinogen were determined in the urine just before and 24 h after each course of treatment. Cisplatin administration was followed by a significant suppression of coproporphyrin and protoporphyrin in red blood cells and coproporphyrin, uroporphyrin, δ-aminolevulinic acid and porphobilinogen in urine. The changes observed paralleled similar changes in haematocrit, red blood cells and haemoglobin, strongly suggesting that cisplatin-induced anaemia may be due to a blocking effect of the drug affecting one or more enzymatic steps in the biosynthesis of porphyrins and haem. A moderate fall in the white blood cell count and a mild fall in platelets together with a steady increase of reticulocytes were also observed during treatment. © 1986 Springer-Verlag.