Search

Background: Fungal infection may be secondary to nasal polyposis or represent a real etiopathogenic factor in the infection itself., Objective: The aim of this study was to evaluate the effectiveness of a combined treatment with lysine acetylsalicylate (LAS) and amphotericin B in preventing recurrence in patients with nasal polyposis with accompanying mycotic infection in comparison with a control group with nasal polyposis and fungal infection who did not receive antifungal therapy., Patients and Methods: A total of 115 patients with nasal polyposis were randomly assigned to 4 different groups and treated as follows: (1) group A, 25 patients were first surgically treated and then treated with LAS; (2) group B, 25 patients received 40 mg of triamcinolone retard intramuscularly 3 times every 10 days (total dose 120 mg) and then they were treated with LAS; (3) group C, 16 patients were surgically treated and then treated with LAS and amphotericin B; (4) group D: 23 patients were treated with a medical polypectomy and steroids (as in the group B) and then with LAS and amphotericin B., Results: We found no significant differences between groups C and D, groups C and A, or groups B and D. However, the recurrence of nasal polyps in the groups treated with amphotericin B plus LAS (C and D) was significantly lower (P = .018) than in the 2 groups treated only with LAS (A and B)., Conclusion: Our results indicate that long term topical treatment with LAS and amphotericin B may be clinically effective in the treatment of patients with nasal polyposis associated with fungal infection.

A family from the Southeast of Italy was found to have a novel beta-globin mutant, beta+45 G-->C, with the features of a silent beta-thalassaemia mutation. It was asymptomatic in two heterozygotes, but its interaction with the severe thalassaemia mutation beta-IVS-II-654 C-->T worsened the haematological and biosynthetic phenotype in two compound heterozygotes; moreover, another compound heterozygote, who was also heterozygote for the alphaalphaalpha(anti3.7), suffered from thalassaemia intermedia. The mutation was found associated in cis with the IVS-II-754 T-->C substitution, which did not lead to abnormally spliced mRNA. Furthermore, the amount of beta+45 mRNA was the same as the betaA mRNA in the reticulocytes of the carriers. In vitro transcription/translation experiments demonstrated that the beta+45 G-->C decreased the efficiency of translation of the beta-globin chain by about 30%: this slight impairment was consistent with the observed clinical phenotype. The beta+45 G-->C is the first mutation found in the Kozak sequence (GACACCATGG) of the beta-globin gene and the first one at the position -6 upstream the ATG. The Kozak consensus sequence plays a major role in the initiation of translation process. The present finding supports the hypothesis that the G in position -6 is important in this process.

Bacterial infections of the respiratory tract account for a large proportion of total medical consultations in general practice. In recent years, antibiotic resistance has increased alarmingly in a number of bacterial species that are common causes of these infections. The aim of this observational study was to determine the antibiotic resistance of microbial agents isolated from patients with acute or acutely exacerbated respiratory infections. Subjects recruited as potential sources of bacteria were either outpatients seen in a number of specialized clinics and hospital practices, or hospitalized patients. Overall, 648 consecutive patients (67% male, mean age 48.1+/-27.0 years) with infection of the upper or lower respiratory tract were observed during a 13-month period. A total of 551 pathogenic microbial strains were isolated and tested for their in vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and ceftriaxone. Among all isolates, the four most frequent pathogens were Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates, 18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46 isolates, 8%). The susceptibility of gram-positive isolates ranged from 97.5% to 95.1%, and no remarkable difference was found in the antibacterial activity of tested b-lactam antibiotics. The susceptibility of gram-negative isolates to piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%, respectively. In contrast, differences were found between piperacillin (or piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone (p<0.0003) in gram-negative isolates. We conclude that, despite the extensive use of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in medical practice during the past three decades, the susceptibility of the most common pathogens involved in the etiology of upper and lower respiratory tract infections to these antibiotics is still high. In particular, bacterial resistance developed by gram-positive organisms against piperacillin is negligible and not alarming.

Type II congenital dyserythropoietic anaemia (CDA-II or HEMPAS) is an autosomal recessive disorder, representing the most frequent form of congenital dyserythropoiesis. It is characterised by normocytic anaemia, variable jaundice and hepato-splenomegaly. Gallbladder disease and secondary haemochromatosis are frequent complications. We report a case characterised by severe transfusion-dependent anaemia. The proband inherited CDA-II in association with beta-thalassaemia trait. Splenectomy did not abolish the transfusion dependence and this, in association with poor compliance to iron-chelation therapy, prompted us to consider bone marrow transplantation (BMT) from his HLA-identical sibling. The preparative regimen included busulfan, thiotepa and fludarabine, and graft-versus-host disease prophylaxis consisted of cyclosporin A and short-term methotrexate. Engraftment of donor cells was prompt and the post-transplant course uncomplicated. The patient is alive and transfusion-independent 36 months after allograft. This is the first case of severe CDA-II to undergo BMT. Analysis of this pedigree suggests that interaction with beta-thalassaemia enhanced the clinical severity of CDA-II, making BMT an attractive therapy for patients with transfusion dependence.

We studied survival and disease complications in 1,146 patients with thalassemia major, born from January 1, 1960 to December 31, 1987. At last follow-up, in March 1997, probability of survival to age 20 years was 89% and to age 25 years was 82% for patients born in the years 1970-1974. Patients who died had a serum ferritin level, measured the year before death, significantly higher than those who survived. Diabetes was present in 5.4% of the patients; heart failure in 6.4%; arrhythmias in 5.0%, thrombosis in 1.1%, hypothyroidism in 11.6%, HIV infection in 1.8%. Hypogonadism was diagnosed in 55% of 578 patients who had reached pubertal age: 83.5% of hypogonadic females and 78.6% of males were receiving substitutive hormonal therapy. In conclusion, the survival of patients with thalassemia major is good and improving, but the prevalence of severe complications is still high.

It is well known that thalassemic patients exhibit an increased frequency of thrombotic events. Most individuals with resistance to activated protein C (APCR) are the result of a point mutation replacing Arg 506 with Gln in the factor V aminoacidic sequence (factor V Leiden). Recently APCR has been shown to account for up to 50% of cases of thrombophilia. In this report, we describe a 10 year old thalassemic intermedia patient heterozygous for Factor V R506Q who developed a stroke following transfusion. Coagulation laboratory values were all within the normal range and there was no evidence of a lupus anticoagulant. Computerized brain tomography showed an ischemic area in the left temporo-parietal region. At follow-up, plasma from the patient demonstrated APCR and molecular diagnostic testing revealed heterozygosity for factor V R506Q. We suggest that the heterozygosity for factor V Leiden could increase the thrombotic risk in thalassemia intermedia. We believe it may be beneficial to screen all intermedia thalassemic patients for APCR especially before starting a transfusional regimen.

Hereditary spherocytosis (HS) is due to different membrane protein defects (i.e., deficiency of spectrin and ankyrin, band 3, or band 4.2). In order to gain new insight into the relationships between band 3 function and proteins associated with the cytoskeleton, we studied erythrocyte anion transport activity in HS characterized by different membrane protein defects. Anion transport activity was increased in HS due to partial band 4.2 deficiency or to band 4.2 absence, while in HS associated with deficiency of spectrin + ankyrin or band 3, the anion transport results were normal or decreased, respectively. Moreover, since HS erythrocytes are characterized by an increased Na and a decreased K, we studied the principal membrane cation transport pathways. Activity of the Na/K pump was increased in all HS studied, while no changes in Na/K/2Cl cotransport and Na/Li exchange were evident between control and HS as well as between forms of HS associated with different membrane protein defects. K/Cl cotransport activity was decreased in all HS studied compared to normal red cells. In all HS, passive membrane permeability to Na and K was increased compared to normal erythrocytes. The increased Na and the low K content can be attributed to the abnormal membrane permeability to cations, which is not related to a specific membrane protein defect.

Sixty patients (31 male and 29 female) with thalassemia major, aged between 6 and 26 years, 18 of which were splenectomized, were observed in this study evaluating the oro-maxillo-facial alterations and correlating them to transfusion indexes, serum ferritin levels, splenectomy and age. For each patient a haematologic and odontostomatologic card was filed with a view to report the medical and clinical history regarding: the haematologic picture, the prevention of caries and parodontal disease, the facies characteristics, the odonto-stomatologic examination, the orthodontic diagnosis, the skull X-rays and the orthopantomography. Poor oral hygiene as well as misknowledge of prevention were generally observed. All the patients showed carious lesions but most of them had never seen a dentist for therapy. The disharmonious growth of splanchnocranium, with the enlargement of the jaw and of its alveolar process, induced by the bone marrow hyperplasia, produced various and serious malocclusion stages (Angle's II class, deep bite, open bite), gnathologic alterations, hypodiaphanous paranasal sinuses and orbital hypertelorism, with a typical oriental-like facies. Malocclusion and the poor oral hygienic conditions determined the occurrence of marginal gingivitis, mainly localized at the level of the lower frontal teeth. In only 3 patients the oral mucous membrane was pale and atrophic. During this investigation agenesia and dental retention were reported in 30% and in 26% of the examined cases respectively, while no patients had supernumerary teeth. Tooth volume, position and shape abnormalities rarely occurred. Only in two patients was enamel hypoplasia described. The caries frequency greatly varied in number and in degree. Only five patients did not show any carious lesions. The caries index (DMF) for the permanent teeth calculated in all the 60 subjects was 5, 12 +/- 4.76. By utilizing Spearman's rank test the number of teeth with caries in the permanent dentition (DFM) and in the mixed dentition (DFM + dmf) was correlated to the average value of ferritin, with the ferritin peak, with transfusion requirements and with the age of the patient at the date of the clinical examination. A significant inverse correlation was therefore demonstrated between transfusion requirements and caries in the mixed dentition. The chi 2 test was used to assess the different frequency of the caries index (above 5) between splenectomized and non-splenectomized patients. Splenectomy proved to be associated only apparently to the total number of patients with more than 5 caries. Conversely, in the non-splenectomized group the frequency of patients with more than 5 caries was definitely lower. Indeed the overall number of caries in both groups of splenectomized and non-splenectomized subjects, of the same average age, was almost identical. Consequently, splenectomy and the higher number of caries are statistically more probable in individuals affected by thalassemia, of increasing age, without however being mutually correlated.

We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic acidosis, complex organic aciduria, and elevation of haemoglobin F and of adenosine deaminase activity. The clinical course was progressive and death occurred at age 19 months. A high proportion of mitochondrial (mt) DNA molecules with a deletion of nucleotides 9238 to 15575 were identified in several tissues; about half of the shortened mtDNA molecules were concatenated to form circular dimers. The clinical and laboratory findings support recent conclusions that Pearson syndrome is not confined to bone marrow and pancreas, as originally described, but is a multi-organ disorder associated with deletions in part of the mtDNA molecules. The tissue distribution and the relative proportions of the abnormal mtDNA molecules apparently determine the phenotype and clinical course.

An epidemiological study was carried out on 114 beta-thalassaemics in order to select those subjects susceptible to hepatitis B virus (HBV) infection for hepatitis B vaccination. The results confirmed the high risk of HBV infection in these patients: 9.6% were HBsAg positive, 29.8% were anti-HBs positive/anti-HBc positive, and 9% were anti-HBc positive. In 60 HBV-negative patients, 20 micrograms doses of hepatitis B vaccine were administered on a schedule of 0, 1 and 6 months. Sera were collected for six years to determine the seroconversion rate and the anti-HBs titre. Seroconversion reached a maximum rate of 93% 12 months after the first vaccination dose and was 80% at the final control (72 months). Highly protective anti-HBs titres were observed until the last control in a high percentage of subjects. The HBVax hepatitis B vaccine has been shown to be safe, immunogenic and effective in beta-thalassaemics.

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.

Selected hemostatic parameters of 23 children affected by beta-thalassemia major were studied and compared to an age- and sex-matched group. Plasma prekallikrein level was reduced in all patients, splenectomized or not. In splenectomized patients, platelet count and in vitro platelet aggregability were significantly increased and Protein C was slightly increased. The activated partial thromboplastin time was prolonged and the normotest reduced. Finally, a reduction in the plasma levels of fibrinogen and of vitamin K-dependent proteins, including the antithrombotic Protein C, was observed in nonsplenectomized patients. Our data indicate that the hemostatic system in patients with thalassemia major may be altered. The relationship between these laboratory changes and clinical manifestations remains to be established.