A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine.

Migraine is a prevalent neurovascular disease with a significant genetic component. Linkage studies have so far identified migraine susceptibility loci on chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92 Australian pedigrees phenotyped for migraine with and without aura and for a more heritable form of "severe" migraine. Multipoint non-parametric linkage analysis revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype (LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele sharing was also observed at multiple different chromosomal regions, some of which overlap with, or are directly adjacent to, previously implicated migraine susceptibility regions. We have provided evidence for two loci involved in severe migraine susceptibility and conclude that dissection of the "migraine" phenotype may be helpful for identifying susceptibility genes that influence the more heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded that the genetic aetiology of the common (International Headache Society) forms of the disease is probably comprised of a number of low to moderate effect susceptibility genes, perhaps acting synergistically, and this effect is not easily detected by traditional single-locus linkage analyses of large samples of affected pedigrees.

[Femoral osteonecrosis in patients treated with radiochemotherapy of Hodgkin's lymphoma]. / Osteonecrosi femorale in pazienti trattati con radio-chemioterapia per linfoma di Hodgkin.

Therapeutic progress has much improved the prognosis of Hodgkin's disease; therefore long-term complications of the treatment have become a major problem. Among these, the authors focused on osteonecrosis of the femoral head, and conducted a retrospective study on 182 patients treated with inverted-Y-field radiation therapy combined to MOPP chemotherapy in 129 cases. Femoral osteonecrosis was found in 6 patients (3.3%), 5 males and 1 female; 4 of them received combined modality treatment (inverted-Y radiation therapy + MOPP), and 2 radiation therapy alone. The interval between the end of treatment and the radiological finding of femoral osteonecrosis ranged from 23 to 54 months, with a mean of 35 months. On the whole, 10 cases of osteonecrosis of the femoral head (4 bilateral, and 2 unilateral) were observed, and 4 fractures involving the anatomic neck. According to our results, neither a safety dose-limit nor an optimal schedule of combination therapy could be fixed. Besides radiological features and the problems of differential diagnosis, the authors considered the pathogenesis of femoral head osteonecrosis in the patients with Hodgkin's disease treated with radiotherapy alone or combined to chemotherapy, and suggested the existence of a personal proneness to the lesion and the role of ionizing radiations, corticosteroids and cytotoxic agents, as inducing factors. Because of the different and unexpected reaction of each patient to the treatment, osteonecrosis prevention is very difficult: however, its complication may be reduced--or even avoided--by subjecting the treated patients to periodic clinical and radiological examinations.

[Lacunae of the occipital bone. Radiological aspects of normal anatomical variants]. / Lacune dell'osso occipitale. Aspetti radiologici di varianti anatomiche normali.

Sixteen patients with lacunar alterations of the squamous occipital bone were studied in various radiographic projections; in many cases tomography and technetium 99m bone scan studies were also performed. In 7 cases lacunae in the cerebral fossa were observed, with an average diameter of 3 cm. These defects were due to a thinning of the inner table of the theca. In 9 cases smaller lacunae were demonstrated bilaterally, which were more radiolucent, isolated or confluent, located in the area corresponding to the internal occipital protuberance at the ridges of the cruciform eminence. The latter were representative of diploic venous lakes, as best demonstrated in lateral projection. This kind of lacunae are considered as anatomic variants, because no bone destruction is demonstrable, as confirmed by technetium scintigraphy.

Critical value of laparotomy with splenectomy in stage III Hodgkin's disease as restaging procedure after chemotherapy.

38 patients with stage III Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse-free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non-lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re-consider the role of laparotomy in stage III HD which should be used as non-routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.

[Splenic irradiation in the treatment of idiopathic myelofibrosis. Retrospective study of 14 cases]. / L'irradiazione splenica nel trattamento della mielofibrosi idiopatica. Studio retrospettivo di 14 casi.

A retrospective study was conducted on 14 patients with idiopathic myelofibrosis after splenic irradiation in order to cure the symptoms due to secondary splenomegaly. Radiation dose ranged from 700 to 2400 cGy, depending on both clinical response and hematological toxicity. Relief of symptoms was observed in all patients (100%); reduction of splenic size ranged from 30 to 70%, with more than 50% reduction in 13/16 cases. Side effects were mild neutropenia and thrombocytopenia, which did not require interruption of treatment; four patients registered a severe anemia. All the hematological side effects stopped with the suspension of treatment. This study shows the beneficial effect of radiation therapy on the symptoms connected to splenomegaly; however, the short duration of response suggests the advantage of splenic low-dose irradiation, to be periodically repeated.

[Idiopathic myelofibrosis. Radiological aspects of bone changes]. / Mielofibrosi idiopatica. Aspetti radiologici delle alterazioni ossee.

Idiopathic myelofibrosis is a chronic myeloproliferative disease characterized by skeletal lesions (30 to 70% of cases). We considered 49 patients with idiopathic myelofibrosis treated between 1972 and 1986 at the Institutes of Hematology and Radiotherapy, University of Bologna. Only 19 of these patients underwent roentgenographic skeletal surveys, associated with whole body bone scintigraphy in 4 cases, and with CT in 1 case. The most common bone change, as seen in 12 patients, was osteosclerosis, following two distinct patterns: pure, and mixed. Other types of bone involvement (osteoporosis and pure osteolysis) were seen in 2 cases only; in 5 patients radiological skeletal examinations did not show meaningful lesions. Conventional radiology is hardly ever conclusive in the diagnosis of idiopathic myelofibrosis. This is due partly to the often moderate degree of bone involvement, partly to the scanty specificity of the findings. However, a careful examination of the plain roentgenographs, completed when possible by other more recent imaging techniques, may be very important towards a more precise definition of the disease and, in some cases, for a correct diagnosis.

[Comparative radiologic study of bone localizations of malignant lymphomas]. / Studio radiologico comparativo delle localizzazioni ossee dei linfomi maligni.

The radiological features of bone lesions in patients affected by malignant lymphoma (Hodgkin's lymphoma, non-Hodgkin's lymphoma and primary non-Hodgkin's lymphoma of bone) were studied. For each bone lesion the site and type of alteration, the involvement of the cortex and adjacent soft tissue, the periosteal reaction and the presence of a pathological fracture were considered. The radiological aggressiveness of bone lesions in malignant lymphoma was assessed on the basis of these data according to Lodwick criteria; the lower aggressiveness of bone lesions of Hodgkin's than in non-Hodgkin's lymphoma is stressed.

Prognostic significance of large mediastinal involvement in Hodgkin's disease.

Relapse rates of 75 patients with previously untreated Hodgkin's disease with stages I and II nodular sclerosis were analyzed according to the mediastinal involvement. The overall relapse rate was 22.6%. The probability of relapse was much greater for patients with large mediastinal involvement (66.6%) compared with 17% for patients with small mass, and 11.7% of patients without mediastinal involvement (P less than 0.001). There was no significant difference in recurrence rates between patients without mediastinal mass and patients with a small mass, and in these patients adjuvant chemotherapy MOPP after radiotherapy showed an evident benefit in reducing the relapse rate. On the other hand, no beneficial effect of adjuvant chemotherapy was observed in patients with large mediastinal involvement. Finally, in the 17 relapsing patients, 'salvage' chemotherapy was less effective in patients with large mediastinal mass than in those with small or no mediastinal involvement.

Management of nodular sclerosis Hodgkin's disease stage I, II A and B: evidence for a beneficial effect of MOPP on the relapse rate.

85 patients with previously untreated Hodgkin's disease with stage I, II A and B nodular sclerosis were treated. 31 of them with stage I and II A were submitted to radiotherapy alone. All are alive, but 9 of them (30%) relapsed. On the contrary, 35 patients with stage I and II A, and 19 with stage I, II and IIE B were submitted to radiotherapy followed by three courses of MOPP. All 54 patients are alive and relapse-free. No severe complication related to chemotherapy was observed. The analysis of results suggests that 3 courses of MOPP can significantly (Ip < 0.00025) reduce the relapse rate in patients with stage I and II nodular sclerosis, eligible for radiotherapy, without increasing morbidity.