Patient advocacy in the 1990s.
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Bone Marrow Transplantation↗
Biomedical subjects
B Weston
Publications and source records attributed to B Weston.
Periorbital varicella gangrenosa necessitating orbital exenteration in a previously healthy adult.
A previously healthy 31-year-old man had profound neurologic compromise and necrotizing periorbital infection due to a complication of varicella infection. Despite aggressive treatment, he required orbital exenteration and radical debridement of the involved tissues. He survived in a vegetative state for almost 1 year before succumbing to progressive neurologic deterioration. We present and discuss this complicated case of varicella gangrenosa to show the devastating nature of complications that can occur from varicella infection in the unsensitized adult.
Adult↗
Use of intraoperative corticosteroids in pediatric tonsillectomy.
OBJECTIVE: To determine the effects of a single dose of dexamethasone sodium phosphate on postoperative morbidity in children undergoing tonsillectomy. DESIGN: Randomized, double-blind, placebo-control clinical trial. SETTING: Academic, tertiary care children's hospital. PATIENTS: Sixty-nine children (35 boys, 34 girls), aged 3 to 18 years, undergoing tonsillectomy with or without adenoidectomy. INTERVENTION: Patients were randomized to receive a single dose of intravenous dexamethasone or saline. MAIN OUTCOME MEASURES: Pain scores, determined by a Faces Scale, were obtained at 4-hour intervals during the first postoperative day and daily for 7 days thereafter. Total use of an analgesic; type of diet; level of activity; presence of halitosis, nausea, emesis, or fever; and incidence of postoperative bleeding were also compared between the two groups. RESULTS: The two groups of children were similar in age, gender, diagnosis, and surgical time. Pain scores in the postoperative period were identical while the patients were in the hospital and for the first 7 days after discharge. No statistically significant differences were noted in pain scores, nausea, emesis, halitosis, analgesic medications required, diet, or activity levels between the two groups of patients. CONCLUSION: A single intraoperative dose of dexamethasone did not appreciably affect postoperative morbidity in children undergoing tonsillectomy.
Adolescent↗
Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4.
Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.
Amino Acid Sequence↗
CD23-mediated homotypic cell adhesion: the role of proteolysis.
CD23 is a multifunctional molecule expressed by cells of lymphoid, myeloid and hematopoietic lineages. As a cell surface molecule CD23 acts both as a low-affinity receptor for IgE (Fc epsilon RII) and as a cell adhesion molecule. CD23 can undergo autoproteolysis to release soluble 37-25-kDa CD23 (s-CD23) molecules with a range of cytokine activities. Here we show a causal link between the two apparently disparate functions of autoproteolysis and cell adhesion. The Epstein-Barr virus-transformed B cell line RPMI-8866 formed macroscopic cell clusters solely via CD23. Cell adhesion was inhibited by mAb to CD23 and by IgE. Cell adhesion was also dependent on serum as cells grown in serum-free media failed to form clusters. In serum-free conditions cell adhesion could be induced by the addition of not only 10% FCS but also s-CD23. As s-CD23 is reported to possess proteolytic activity we screened a range of proteases to determine whether they also could induce cell adhesion in serum-free medium. It was found that chymotrypsin and elastase induced cell:cell adhesion in RPMI-8866 cells. The same panel of proteases were screened against a range of CD23-positive (Jijoye, AF-10, T2, U937, ICH-1) and CD23-negative (RPMI-8226, U266, MOLT-4, Ramos) cell lines. It was found that chymotrypsin and elastase induce cell adhesion only in cells expressing CD23. Peptide mapping studies showed that chymotrypsin and elastase cleaved immunoprecipitated CD23 near the same site by which 37-kDa s-CD23 is released (Ala 80). Serum demonstrated no proteolytic activity towards CD23. However, it was found that cells grown in serum-free medium released 25-kDa s-CD23 without the need for prior cleavage at the 37-kDa cleavage site. To confirm the role of proteolysis in CD23-mediated cell adhesion we screened a range of protease inhibitors for their ability to antagonize this process. It was found that tosyl-lysine chloromethyl ketone inhibited CD23-mediated cell adhesion. Lactoperoxidase treatment, which inhibits CD23 cleavage, also inhibited cell adhesion. Addition of chymotrypsin and elastase to lactoperoxidase-treated cells induced cell adhesion. From these data we propose that intact CD23 has no demonstrable role in cell adhesion; instead, the portion of CD23 remaining on the cell surface following cleavage appears to mediate cell adhesion.
Blood Physiological Phenomena↗
Clinical and biologic effects of granulocyte colony stimulating factor in the treatment of myelokathexis.
Successful treatment of a patient with myelokathexis, a rare form of chronic neutropenia associated with recurrent infections, is described. Rapid mobilization of bone marrow neutrophils and improved myeloid morphologic features were observed after treatment with human granulocyte colony stimulating factor. Transient thrombocytopenia and bone pain were observed during treatment. Although neutrophil chemotaxis, superoxide production, and FcRIII surface expression were reduced, the patient improved clinically after restoration of a normal neutrophil count.
Antigens, CD↗
Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor.
We studied neutrophil function and clinical responses in seven patients with severe congenital neutropenia (SCN) after they received treatment with recombinant human granulocyte colony stimulating factor (rhG-CSF). Two subpopulations of patients with SCN were defined by their pattern of absolute neutrophil response, superoxide production, and cytochrome b559 levels. One group had an oscillating absolute neutrophil count and reduced ability to produce superoxide and cytochrome b559 (n = 4), and the second group had a relatively constant absolute neutrophil count response with normal superoxide and cytochrome levels (n = 3). Neutrophils from both groups had decreased surface expression of FcRIII and abnormal upregulation of the C3bi receptor (CR3). All patient neutrophils, however, had normal contents of the primary granule constituent, beta-glucuronidase, and the specific granule constituent, vitamin B 12 binding protein. The clinical response to rhG-CSF was evident by marked improvement in the degree of periodontitis and reduction in the number of oral ulcers in both groups of patients. Although neutrophil function is not completely normal in patients with SCN, it is likely that enough redundancy exists in neutrophil bactericidal capacity to promote normal host response to inflammation.
CD18 Antigens↗
Ceftazidime versus placebo in respiratory exacerbations of cystic fibrosis.
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Ceftazidime↗
Effects of socioeconomic and clinical factors on survival in multiple myeloma.
It was recently reported that low socioeconomic status (SES) in multiple myeloma (MM) patients is associated with a poorer prognosis. To reassess this finding in another group of MM patients, we used data from interviews of 153 MM patients seen at Duke University Medical Center over a 6-year period. Medical records were also reviewed for data on traditional clinical prognostic factors. Using proportional hazard survival analysis, no SES variables were associated with survival. Current income, highest income, occupation, type of dwelling, years of education, and crowding did not enter the stepwise regression model at alpha = .10. In contrast, many clinical factors predicted prognosis (calcium, P = .019; percent plasma cells on initial bone marrow, P = .019; history of transfusions, P = .015; WBC count, P = .007; pathologic fractures, P = .001; and urate, P less than .001). Thus, we do not confirm the previously reported association between social class and myeloma survival.
Aged↗
Familial aggregation of melanoma, basal cell carcinoma, and gastric adenocarcinoma.
A family with four cases of melanoma, seven cases of basal cell carcinoma, and two cases of gastric adenocarcinoma, is described. The proband, who had three different primary tumors, died of gastric cancer, as did his father. Four of the proband's six siblings were affected with melanoma or basal cell cancer, as were two of his three children. Both daughters of one melanoma patient developed basal cell cancers. No spouses were affected, the cases were widely separated in time and place, and no unusual exposures were reported. HLA analysis of affected and unaffected first-degree relatives showed no association with antigens previously described in familial melanoma or segregation with a specific HLA haplotype. Although there was no association with HLA phenotype, these results suggest that melanoma, basal cell carcinoma, and gastric adenocarcinoma can be inherited in an autosomally dominant pattern similar to other familial tumor syndromes.
Adenocarcinoma↗
The diagnosis and treatment of major depressive disorder in childhood.
The authors review the evidence supporting the hypothesis of similarity or identity of prepubertal and adult major depressive disorders and give a state-of-the-art account of current assessment techniques, diagnosis, and treatment methods of prepubertal major depression. This is an area of child psychiatry where recent psychobiological research advances are fueling profound changes in traditional nosology and therapeutics. In addition, further understanding of early onset major depression is likely to throw considerable light on the nature and pathophysiology of depressive illness across ages.
Adolescent↗
A technique for removing an impacted postnasal pack.
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Epistaxis↗
Stability of the postoperative alignment in adjustable-suture strabismus surgery.
We reviewed the postoperative alignment drift in 201 patients between the ages of 14 and 75 years who underwent rectus muscle surgery with adjustable sutures from 1984 to 1989. We analyzed results for 42 primary esotropia (ET) surgeries and 37 reoperations (groups IA and IB, respectively), 34 exotropia (XT) primary surgeries and 66 reoperations (groups IIA and IIB, respectively), and 22 hypertropia (HT) surgeries (group III). Forty percent of patients required postoperative muscle adjustment. All patients underwent a minimum of 8-weeks follow up; 66% underwent 6-months follow up or longer. The postoperative drifts in alignment for primary surgeries versus reoperations were not significantly different for either ET or XT patients. The mean postoperative drift in prism diopters from the alignment immediately after the adjustment, or after the surgery if no adjustment was needed, for each group as measured during the most recent follow up was 1.3 eso-shift for group IA, 1.2 exo-shift for group IB, 4.8 exo-shift for group IIA, 4.1 exo-shift for group IIB, and 1.5 hyper-shift for group III. Only for groups IIA and IIB were these drifts found to differ significantly from zero. Based on these drift patterns, we align ET patients to orthotropia, XT patients to 5 to 7 delta esotropic, and HT patients to 1 to 2 delta hypotropic positions.
Adolescent↗