Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.

We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele (*)04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2(*)04 peaked at 31%. The IGHV1-2(*)04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2(*)04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97-99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2(*)04 allele.

Somatic mutations of KIT in familial testicular germ cell tumours.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.

The effects of five years of nocturnal cuirass-assisted ventilation in chest wall disease.

We investigated the long-term effectiveness of cuirass-assisted ventilation, and examined whether mortality and morbidity could have been predicted at the time of admittance. Twenty five patients were commenced on nocturnal cuirass-assisted ventilation between 1983 and 1985, 10 with scoliosis or kyphosis, 8 with a thoracoplasty and 7 with neuromuscular disease. Mean pretreatment vital capacity was 30% of predicted, and arterial carbon dioxide tension (Paco2) was 8.2 kPa (62 mmHg). Fifteen patients were alive 5 yrs later. Two had discontinued assisted ventilation, both dying soon afterwards, and three had been changed to intermittent positive pressure ventilation. Survival could not have been predicted from age, severity of disease, lung volumes or arterial blood gases at presentation. Paco2 in the survivors had risen from a mean of 6.1 kPa (46 mmHg) after one year to 6.8 kPa (52 mmHg) after 5 yrs (p < 0.05), but remained significantly less than at presentation. There were no significant change in arterial oxygen tension (Pao2), lung volumes, respiratory muscle strength, haemoglobin, right heart failure, exercise tolerance, mental function and symptom scores after 5 yrs, compared to after 1 yr. The median amount of time spent in hospital declined from 15 days per patient in the first year after initial discharge with cuirass-assisted ventilation, to between 3-5.5 days per patient in subsequent years. We conclude that nocturnal cuirass-assisted ventilation has a role in long-term management of patients with neuromuscular and skeletal chest wall disorders. A randomized comparison with nasal intermittent positive pressure ventilation is now indicated.

The effects of one year of nocturnal cuirass-assisted ventilation in chest wall disease.

The effects of one year of nocturnal cuirass-assisted ventilation using individually designed cuirass respirators have been investigated in twenty-five patients with chest wall disease. After one year, 22 (88%) of the patients were alive. Daytime arterial blood gases had improved. Functional residual capacity (FRC) had increased but there was no significant change in other lung volumes. Maximum inspiratory pressure (MIP) improved in the subjects with a scoliosis but not in those with a thoracoplasty or neuromuscular disease. Maximum expiratory pressure (MEP) was unchanged. Maximum voluntary ventilation (MVV), the ventilatory response to carbon dioxide and six minute walking distance had all increased. There was no improvement in respiratory symptoms, but a decrease in depression scores and in the time taken to complete a trail test. The mean (SD) number of days spent in hospital over the year was 21.5 (15.1) per patient, with patients consulting their general practitioners less frequently than in the year prior to commencing nocturnal cuirass-assisted ventilation. The cost of commencing a patient on domiciliary nocturnal cuirass-assisted ventilation is estimated as 2470 pounds, and of maintaining them at home for one year as 3302 pounds.