Human erythrocyte protein 4.2 deficiency associated with hemolytic anemia and a homozygous 40glutamic acid-->lysine substitution in the cytoplasmic domain of band 3 (band 3Montefiore)

Red blood cell (RBC) protein 4.2 deficiency is often associated with a moderate nonimmune hemolytic anemia, splenomegaly, and osmotically fragile RBCs resembling, but not identical to, hereditary spherocytosis (HS). In the Japanese type of protein 4.2 deficiency (protein 4.2Nippon), the anemia is associated with a point mutation in the protein 4.2 cDNA. In this report, we describe a patient with moderate and apparently episodic nonimmune hemolytic anemia with splenomegaly, spherocytosis, osmotically fragile RBCs, reduced whole cell deformability, and abnormally dense cells. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis analysis of the proposita's RBC membrane proteins showed an 88% deficiency of protein 4.2 and a 30% deficiency of glyceraldehyde-3-phosphate dehydrogenase (band 6). Structural and molecular analyses of the proposita's protein 4.2 were normal. In contrast, limited tryptic digestion of the proposita's band 3 showed a homozygous abnormality in the cytoplasmic domain. Analysis of the pedigree disclosed six members who were heterozygotes for the band 3 structural abnormality and one member who was a normal homozygote. Direct sequence analysis of the abnormal band 3 tryptic peptide suggested that the structural abnormality resided at or near residue 40. Sequence analysis of the proposita's band 3 cDNA showed a 232G-->A mutation resulting in a 40glutamic acid-->lysine substitution (band 3Montefiore). Allele-specific oligonucleotide hybridization was used to probe for the mutation in the pedigree, showing that the proposita was homozygous, and the pedigree members who were heterozygous for the band 3 structural abnormality were also heterozygous for the band 3Montefiore mutation. The band 3Montefiore mutation was absent in 26 chromosomes from race-matched controls and in one pedigree member who did not express the band 3 structural abnormality. In coincidence with splenectomy, the proposita's anemia was largely corrected along with the disappearance of most spherocytes and considerable improvements of RBC osmotic fragility, whole cell deformability, and cell density. We conclude that this hereditary hemolytic anemia is associated with the homozygous state for band 3Montefiore (40glutamic acid-->lysine) and a decreased RBC membrane content of protein 4.2. We speculate that band 3 structural abnormalities can result in defective interactions with protein 4.2 and band 6, and in particular, that the region of band 3 containing 40glutamic acid is involved directly or indirectly in interactions with these proteins.     

Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study

OBJECTIVES: To assess the activity of vinorelbine in women with recurrent or resistant epithelial ovarian cancer following treatment with platinum and paclitaxel in terms of survival rate at 6 months, objective response rate (in the subset of patients with bidimensionally measurable disease), and health-related quality of life. METHODS: Seventy-nine evaluable patients with progressive ovarian cancer following platinum and taxane therapy received vinorelbine 30 mg/m(2) days 1 and 8 of a 21-day treatment cycle. RESULTS: Six-month survival rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1 months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0 complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%). Patients reported substantial symptom-related distress at baseline, which persisted, but did not worsen, during treatment. Patients also had impaired physical functioning at baseline and this continued to decline during treatment. CONCLUSIONS: The 6-month survival rate achieved with salvage vinorelbine is comparable to the results obtained with other salvage therapies in patients with relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine did not appear to be effective in alleviating the symptom-related distress or progressive impairment of physical functioning associated with this disease.     

Hypersensitivity pneumonitis: evaluation with CT

Thirteen chest radiographs and computed tomographic (CT) scans obtained from 11 patients with hypersensitivity pneumonitis were reviewed. The CT findings were correlated with open lung biopsy findings in seven patients. The two patients with acute hypersensitivity pneumonitis showed air-space opacification on CT scans. An open lung biopsy, done in one of these patients, demonstrated noncaseating granulomas and filling of the air spaces with macrophages. The nine patients with subacute hypersensitivity pneumonitis showed small, rounded opacities and patchy air-space opacification on CT scans. These findings reflected the histologic findings, which consisted of interstitial pneumonitis, cellular bronchiolitis, and small, noncaseating granulomas. The six patients with symptoms for 12 months or longer also showed irregular linear opacities on CT scans, corresponding to areas of fibrosis. CT scans were superior to radiographs in helping to assess the type and extent of abnormalities, and high-resolution CT scans were superior to conventional CT scans.     

Rocky Mountain spotted fever

Rocky Mountain spotted fever (RMSF) is an unusual but important dermatological condition to identify without hesitation. The classic triad of headache, fever, and a rash that begins on the extremities and travels proximally to involve the trunk is found in a majority of patients. The cutaneous centripetal pattern is a result of cell to cell migration by the causative organism Rickettsia rickettsii. Such individuals should receive prompt antimicrobial therapy and supportive care to avoid serious and potentially fatal complications.     

Severe outcomes of allogeneic and autologous blood donation: frequency and characterization

BACKGROUND: There are few published data on severe outcomes of the donation of blood for allogeneic or autologous use. It would be helpful if blood collectors could better characterize and/or predict the likelihood of significant complications of blood donation. STUDY DESIGN AND METHODS: Very severe outcome (VSO) was defined as an event requiring hospitalization. Approximately 4.1 million American Red Cross whole-blood donation records (July 1993-March 1994) were reviewed for the incidence and type of VSO. RESULTS: A total of 33 VSOs occurred for all donations. The incidence of VSOs for allogeneic donation was 1 (0.0005%) in 198,119 and that for autologous donation was 1 (0.006%) in 16,783 (p < 0.001). First-time donors were three times as likely to have a VSO. Donors > 40 years old had 87.9 percent of the VSOs, and donors > 60 years old had 48.5 percent. Vasovagal (66.7%) and anginal (12.1%) episodes were the most frequent complications, and 66.7 percent of reactions occurred at the blood collection site. The mean hospital stay was 1.9 days. CONCLUSION: VSO is an infrequent complication of all types of blood donation, but its occurrence may be associated with significant morbidity and cost. VSO is nearly 12 times as likely in autologous blood donors.