Germline mutations in the PTEN gene in Israeli patients with Bannayan-Riley-Ruvalcaba syndrome and women with familial breast cancer.

Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

Successful treatment of invasive aspergillosis in chronic granulomatous disease by granulocyte transfusions followed by peripheral blood stem cell transplantation.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impaired microbial killing and susceptibility to bacterial and fungal infections. Cure of the disease can be achieved by stem cell transplantation when performed early in its course, and before severe infections have developed. Invasive aspergillosis constitutes a very high risk for transplantation. We report a 4-year-old boy with X-linked CGD who underwent successful HLA-identical peripheral blood stem cell (PBSC) transplantation during invasive pulmonary aspergillosis and osteomyelitis of the left fourth rib, which was unresponsive to antifungal treatment. During the 2 months prior to the transplant he received G-CSF-mobilized granulocyte transfusions (GTX) from unrelated donors three times a week in addition to the antifungal treatment. This resulted in clinical improvement in his respiratory status. He also received GTX during the aplastic period after the conditioning regimen, until he had engrafted. Post-transplant superoxide generation test revealed that neutrophil function was within normal range. One year post transplant the CT scan showed almost complete clearance of the pulmonary infiltrates and a marked improvement in the osteomyelitic process. Based on other reports and our own experience, GTX can serve as important treatment in patients with CGD who have failed conventional anti-fungal treatment and for whom stem cell transplantation is the only chance for cure.

The role of a secondary pediatric ambulatory care service within the community.

OBJECTIVE: To describe the establishment and function of a secondary pediatric ambulatory care service within the community, to assess the utilization of a pediatric community service ("The Center"), and to assess parents' degree of satisfaction with the quality of care in the center. DESIGN: Personal information and information regarding all visits was recorded and analyzed. A structured telephone interview was used to evaluate parents' satisfaction with the quality of care in the center. SETTING: A pediatric community centre managed by board certified pediatricians. The clinic offers primary and secondary care. PARTICIPANTS: A random sampling of parents of children who visited the center (n = 615). RESULTS: The number of children treated in the center increased five-fold within three years. Most visits took place during evening hours and over the weekends. The most common presenting symptoms were fever, respiratory and gastrointestinal complaints, earache, and trauma. Eighty-nine percent of parents were satisfied or very satisfied with the quality of care in the center; 95% were satisfied or very satisfied with the attitudes of physicians and nurses providing treatment. CONCLUSION: The center is widely utilized by parents with a great degree of satisfaction. The availability and extended working hours of the center provided medical care for a large number of children seeking "after hours" medical attention, as well as a backup for the primary care physicians. The center, therefore, provides a model for improved quality of medical care within the community.