De novo subgaleal abscess

The authors report a case of spontaneous subgaleal abscess formation in a 62-year-old woman without antecedent trauma or injury. She presented with occipital scalp pain and swelling which rapidly became generalized two days following recovery from an upper respiratory infection. Diagnosis was based on radiological examination and aspiration of the subgaleal space, which yielded a purulent exudate with a pure growth of Streptococcus pyogenes. Initial management with incision, drainage and parenteral antimicrobial therapy was not successful. Operative exploration of the subgaleal space revealed extensive necrosis of the galea aponeurotica, and bone curettings revealed microscopic evidence compatible with osteomyelitis. Management with debridement and excision of all necrotic tissue plus prolonged parenteral antimicrobials was successful. Subgaleal abscess formation without an overlying wound or previous trauma has not been reported previously.     

Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse

We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host- type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T- cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T- cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.     

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates: I. Effects of anti-T11 antibodies on the circulating T cell pool

The effects of in vivo administration of three monoclonal antibodies specific for T11, the E rosette receptor on T lymphocytes, were examined in the rhesus monkey (Macaca mulatta). These three monoclonal antibodies were of different isotypes and were shown in in vitro studies to have differing affinities for the monkey T11 structure. Furthermore, each antibody induced antigenic modulation of T11 from the cell membrane of the lymphocytes to varying degrees in vitro. In vivo infusion of each of these antibodies into normal rhesus monkeys caused remarkably different effects on the circulating T lymphocyte pool. Infusion of these antibodies at doses of 2 mg/kg caused the coating of circulating T lymphocytes with antibody, the modulation of T11 off the T cell surface and the transient clearance of T cells from the circulation. Yet, the variation in the extent to which these effects were seen with these different antibodies indicates that extrapolating from studies of the in vivo use of one antibody to the use of another may be quite difficult. These studies clearly indicate the strengths of this nonhuman primate system for exploring the uses of monoclonal antilymphocyte antibodies as therapeutic agents. They, however, also demonstrate that differences may exist in the affinity of a particular antibody for homologous lymphocyte surface structures in humans and in a nonhuman primate species. These differences may make it difficult to predict the precise effects that the infusion of an antibody will cause in humans on the basis of alterations it induces in nonhuman primates.     

Absence of breast cancer cells in a single-day peripheral blood progenitor cell collection after priming with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte- macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA- positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.     

Ras oncogene mutations are rare late stage events in chronic myelogenous leukemia

DNA from bone marrow and peripheral blood samples of 44 chronic myelogenous leukemia (CML) patients were analyzed for the presence of mutations of codons 12, 13 or 61 of the N-ras, H-ras, or K-ras genes. In seven patients, samples were available from both their chronic phase and blast crisis. A total of 29 samples examined were at chronic phase and 22 were at blast crisis (eight lymphoid, eight myeloid, and six undifferentiated). No mutations were identified in N-ras or H-ras. Two patients in myeloid blast crisis had K-ras mutations, one patient at codon 12, the other at codon 13. In the former patient the mutation was not present and the latter patient was not tested in chronic phase. Our findings indicate ras mutations are an infrequent late stage event in CML that occur in myeloid blast crisis.     

Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: A meta-analysis

BACKGROUND & AIMS: Esophagitis healing proportions are often incorrectly called the healing rate. The aim of this study was to compare different drug classes by expressing the speed of healing and symptom relief through a new approach. METHODS: A fully recursive literature search to July 1996 identified 43 articles on gastroesophageal reflux disease (GERD) (7635 patients) meeting strict inclusion criteria: single- or double-blind randomized studies in adults with endoscopically proven erosive or ulcerative esophagitis. For each drug class, linear regression analysis estimated the average percentage of patients who were healed and heartburn free per week. RESULTS: Mean overall healing proportion irrespective of drug dose or treatment duration (< or =12 weeks) was highest with proton pump inhibitors (PPIs; 83.6% +/- 11.4%) vs. H2-receptor antagonists (H2RAs; 51.9% +/- 17.1%), sucralfate (39.2% +/- 22.4%), or placebo (28.2% +/- 15.6%). Correcting for patients without baseline heartburn, the mean heartburn-free proportion was highest with PPIs (77.4% +/- 10.4%) vs. H2RAs (47.6% +/- 15.5%). PPIs showed a significantly faster healing rate (11.7%/wk) vs. H2RAs (5.9%/wk) and placebo (2.9%/wk). PPIs provided faster, more complete heartburn relief (11.5%/wk) vs. H2RAs (6.4%/wk). CONCLUSIONS: More complete esophagitis healing and heartburn relief is observed with PPIs vs. H2RAs and occurs nearly twice as fast. This semiquantitative expression of speed of healing and symptom relief permits comparisons for future economic evaluation and quality-of-life assessments. (Gastroenterology 1997 Jun;112(6):1798-810)     

BCL2 translocations in leukemias of mature B cells

Although translocations of the BCL2 gene are frequent in B-cell non- Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B- cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B-CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI- HindIII fragment indicating a clustering of breakpoints. Two cases of B- CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms.