Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.     

Poikilocytic hereditary elliptocytosis associated with spectrin Alexandria: an alpha I/50b Kd variant that is caused by a single amino acid deletion

Hereditary elliptocytosis (HE) is a heterogeneous disorder of red blood cells frequently associated with abnormal limited tryptic digestion of the alpha I domain of spectrin and impaired spectrin dimer self- association. We studied two related individuals with poikilocytic hereditary elliptocytosis (HE) of different severity. Limited tryptic digestion of spectrin from these individuals showed the presence of a variant alpha I/50b Kd peptide at the expense of the normal alpha I/80 Kd peptide. Amino acid sequence analysis of the abnormal peptide showed that the proteolytic cleavage occurred after the arginine at position 470 of the alpha spectrin chain. Spectrin from these patients had an impaired ability to undergo self-association, as evidenced by increased amounts of spectrin dimers in 4 degrees C extracts of erythrocyte membrane from affected individuals. The polymerase chain reaction was used to study the DNA sequence of the alpha spectrin gene encoding the region of the alpha spectrin chain surrounding the abnormal proteolytic cleavage site. We detected the in-frame deletion of the trinucleotide CAT, encoding histidine 469, two amino acid residues to the N-terminal side of the abnormal proteolytic cleavage site between residues 470 and 471. Similar to many other defects of spectrin associated with HE, this deletion occurs in helix three of repeat 5 of the proposed triple helical model of spectrin repeats.     

Laparoscopic repair/peritoneal toilet of perforated duodenal ulcer

Summary Laparoscopic techniques have been refined to the point where exposure, haemostasis and tissue approximation by suture approach those obtained at open access surgery. We report a patient with acute perforation of an ulcer in the first part of the duodenum who was successfully treated by laparoscopic oversewing and omental patching. The clinical indications for contemplating use of laparoscopic surgery for acute ulcer perforation, techniques employed and the areas for potential improvement of instruments, needles and sutures are discussed.     

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1)

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.     

Development of the retinofugal projections in the embryonic and larval zebrafish (Brachydanio rerio)

Studies of the projection from the vertebrate retina have contributed significantly to current concepts of neural development. The zebrafish has recently become a favored system for the study of development in general and neural development in particular. Although the development of both the optic nerve and the retinotectal projection of the zebrafish has been described, the retinofugal projection in its entirety has not. This paper describes it and also addresses the issue of projectional exuberance: i. e., transient projections to targets that are not innervated in the adult. The retinofugal projection of embryonic and larval zebrafish (32 hours to 7 days post-fertilization) was labeled by intraocular injection of DiI (1,1′-dioctadecyl-3,3,3′,3′, tetramethylindocarbocyanine perchlorate) and then studied in wholemounts and sections. The first optic axons crossed the chiasm at 32 hours post-fertilization and projected in a straight line to reach the tectum at about 44 hours. At 48 hours, a few optic axons deviated along either the tract of the posterior commissure or the tract of the postoptic commissure. By 72 hours (about the time of hatching) optic axons arborized in ten distinct regions, termed arborization fields. At 6–7 days post-fertilization, the same ten arborization fields (nine contralateral, one bilater) were evident. Most of the arborization fields were located in the superficial neuropil and were not associated with morphologically identifiable clusters of somata. On the basis of various landmarks, the ten arborization fields are identified as precursors of retinorecipient nuclei previously described in other adult cypriniform fishes. The development was characterized by the nearly complete absence of any transient projections. Thus, the idea that axonal outgrowth is initially exuberant and trimmed back later is not supported by these results. © 1994 Wiley-Liss, Inc.     

"Una mujer trabaja doble aqui": Vignette-based focus groups on stress and work for Latina blue-collar women in eastern North Carolina

Latina women are a growing percentage of the working population, and very little is known about their health needs and interests. The purpose of this article is to share qualitative research results gathered from Latina women with a particular focus on exploring stress and health. This project was a substudy of Health Works in the Community, a 5-year CDC-funded multiple risk-factor reduction trial using participatory action research approaches to address smoking, healthy eating, stress, and physical activity among blue-collar women from 12 manufacturing work sites in rural, eastern North Carolina. Five focus groups were conducted with trained, bilingual facilitators using a vignette-based moderator guide that appeared particularly effective with this population. Results from the focus groups are used to make recommendations for future research with Latinas and for developing effective work-site-based interventions to address issues of stress and health within this population.