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Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation.

Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19 patients with persisting mixed chimerism (MC) among 231 patients transplanted with partially T cell-depleted stem cell grafts from HLA-identical siblings. Persisting MC is defined as MC for more than 2 years in patients without any evidence of relapse. Median leukemia-free survival in these patients was 150 (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the long-term follow-up of MC and definition of patterns of chimerism in the various subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4 lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes), CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+) (NK-cells) were analyzed. The majority of patients with persisting MC were conditioned with a less intensive conditioning regimen and had little GVHD. Sequential monitoring of the chimerism resulted in a group of patients (n = 7) with very slow transient mixed chimerism that resulted in complete DC after median 7 years. Another nine patients had a relatively high percentage of persisting autologous cells for a median of 12 years and in three patients we observed a stable low percentage of autologous cells. Only two out of 19 patients (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was analyzed at a median of 8 years after SCT in nine patients. In five patients mixed chimerism simultaneously detected by RCP and CYT was associated with MC in all subsets. Within each individual patient the percentages of donor and recipient cells were very different between the different subsets. Two CML-CP1 patients were mixed chimera in only two subsets and in one patient these subsets represented pending relapse. In another two patients mixed chimerism with a very low number of autologous red cells was not found in the PBMCs because of the different sensitivity level of the RCP and the PCR-STR technique. We conclude that in patients with persisting mixed chimerism after partially T cell-depleted SCT a remarkable number of patients had lymphoid malignancies, the majority of the patients were conditioned with less intensive conditioning regimens and the mixed chimerism was not correlated with relapse. Chimerism in granulocytes and PBMC subsets did show great intra-individual differences in the subsets and these data correlated well with RCP and CYT data with the exception of the NK cells.

Adolescent↗

In situ EPR investigation of the addition of persistent benzyl radicals to acrylates on ZSM-5 zeolites. Direct spectroscopic detection of the initial steps in a supramolecular photopolymerization.

Photolysis of dibenzyl ketone derivatives adsorbed on ZSM-5 zeolites produces persistent benzyl radicals (initiator radicals), which add to methyl acrylates (monomers) to generate persistent adduct radicals. Both initiator and adduct radicals are readily observable by conventional steady-state EPR spectroscopy at room temperature and are persistent for time periods ranging from seconds to many days. The rate of the formation and the amount of the adduct persistent radical formed depends on the structure of the initiator radical (benzyl radical derivative) and the structure of the monomer (acrylate derivative). The lifetimes of the initiator and adduct radicals depend on the supramolecular structure of the radical@zeolite complex and the diffusion and reaction dynamics of the radicals in the complex. The most intense signal and highest addition rate to methyl acrylate were observed for the smallest initiator radical, the benzyl radical, because of its high mobility and relatively rapid diffusion within the internal zeolite surface. With increasing length of an alkyl chain (methyl, ethyl, and pentyl) on either the initiator (alpha position of the radical) or monomer (alkyl group of acrylate ester), the rate of radical addition to the monomer decreased, a result that is consistent with the decreased mobility and diffusion of the initiator radical or monomer. Deuterium isotope experiments and variation of the methyl acrylate concentration demonstrated that the initial adduct radical from methyl acrylate adds to another methyl acrylate to generate a secondary adduct radical, which, in turn, can continue to propagate to form a polymer that is cross-linked to the zeolite crystals. The results demonstrate that EPR can be a powerful tool for the direct in situ analysis of supramolecular photochemistry involving radicals rendered persistent by supramolecular steric effects. The latter eliminate the need for sophisticated flash photolysis equipment to investigate the structure and dynamics of reactive radicals and require only the use of simpler steady-state lamps.

Journal Article↗

Early childhood stuttering I: persistency and recovery rates.

The divergent developmental course of stuttering with its two major paths, persistency and spontaneous (unaided) recovery, has been a focus of scientific attention because of its critical theoretical, research, and clinical perspectives. Issues concerning factors underlying persistency and recovery and their implications for early intervention have stirred considerable controversy among scientists. In light of the intense interest, the scarcity of direct essential epidemiological data concerning the magnitude of the two paths and the timing of recovery is problematic. Most past studies have used retrospective methodologies. The few longitudinal studies have been severely limited in scope or objective data. The purpose of the investigation reported herein is to study the pathognomonic course of stuttering during its first several years in early childhood with special reference to the occurrence of persistent and spontaneously recovered forms of the disorder. Employing longitudinal methodology with thorough, frequent periodic follow-up observations, multiple testing, and recording of extensive speech samples, 147 preschool children who stutter have been closely followed for several years from near the onset of stuttering. In this, the first of three related articles, we present findings regarding the current stuttering status of 84 of these children, who have been followed for a minimum of 4 years after their onset of stuttering. The data indicate continuous diminution in the frequency and severity of stuttering over time as many children progressed toward recovery. Our findings lead to conservative estimates of 74% overall recovery and 26% persistency rates. The process of reaching complete recovery varied in length among the children and was distributed over a period of 4 years after onset. Detailed analyses of phonological and language skills pertaining to differentiation of the developmental paths of children who persist and those who recover are presented in the two other articles in the series (E. P. Paden et al., 1999, and R. V. Watkins et al., 1999).

Age Factors↗

Effect of adrenergic blockade on the pheromonal restoration of cyclic activity in young oestrogen-primed persistent oestrous female rats.

The effects of adrenergic blockade on pheromonal restoration of cyclic activity were studied in acute oestrogenized persistent oestrous young female rats. Hypothalamic luteinizing hormone-releasing hormone (LHRH) and plasma LH, follicle-stimulating hormone (FSH), oestradiol and progesterone were measured by specific radio-immunoassays, and prolactin by enzyme-linked immunosorbent assay in: (i) young cycling rats; (ii) young persistent oestrous female rats; (iii) young persistent oestrous females treated with nasal sprays of male urine; and (iv) young persistent oestrous females treated with nasal sprays of male urine and injected with saline, propranolol, prazosin or yohimbine. LHRH was low 24 h after oestradiol benzoate injection, increasing up to 15 days later; LH, FSH, oestradiol and progesterone ranged from high values 24 h after oestradiol benzoate injection to low 15 days later; prolactin ranged from low concentration 24 h after oestradiol benzoate injection to high 15 days later. Male urine treatment induced a depletion of LHRH, a rise of LH, FSH and progesterone, pheromonal restoration of cyclic activity and a normal hormonal cyclic pattern. Treatment with prazosin and yohimbine prevented the pheromonal restoration of cyclic activity, the drop of LHRH and the rise of plasma concentration of the studied hormones induced by male urine, while saline or propranolol did not. These results show the hormonal pattern of the pheromonal restoration of cyclic activity in persistent oestrous rats and strongly suggest that alpha-adrenergic inputs to the hypothalamus may be involved in this pheromonal effect.

Administration, Intranasal↗

Impaired bioavailability of vitamin A in adults and children with persistent diarrhoea in Zambia.

BACKGROUND: We have previously demonstrated a strong relationship between low serum retinol concentration and mortality in Zambian AIDS patients with diarrhoea, but were unable to detect any benefit from oral micronutrient supplementation. AIM: To test the hypothesis that this is related to impaired availability of vitamin A, we analysed serum retinol concentration changes over 6 h following oral mega-dose therapy (60, 120 or 180 mg retinol). METHODS: Twenty-four men without diarrhoea, 15 adults with persistent diarrhoea and 11 children (six girls, five boys) with persistent diarrhoea were studied. RESULTS: Men with persistent diarrhoea had lower baseline serum retinol concentrations (median 0.39 micromol/L, interquartile range 0.21-0.56) than controls (median 1.16 micromol/L, interquartile range 0.84-1.47; P=0.0003). After 60 mg retinol, the rise in serum retinol in HIV seropositive controls (median 0.63 micromol/L, interquartile range 0.35-0.77) did not differ significantly from that observed in HIV seronegative controls (median 0.35 micromol/L, interquartile range - 0.04-0.56; P=0.20). Increasing the dose to 120 mg or 180 mg retinol did not enhance the increase in serum retinol concentration. The increase in serum retinol was less in adults with persistent diarrhoea (median 0.25 micromol/L, interquartile range 0.04-0.35) and in children (median 0.11 micromol/L, interquartile range 0.04-0.46) than in men without diarrhoea (median 0.44 micromol/L, interquartile range 0.26-0.74; P=0.03). Adults and children with diarrhoea had greater losses of retinol in urine over a 24-h period than controls, but less than 1% of the ingested dose was excreted. CONCLUSIONS: These results suggest that persistent diarrhoea in this population is associated with reduced bioavailability of retinol. Further work is required to determine the metabolic fate of therapeutic doses of retinol and to determine appropriate replacement strategies for HIV infected individuals.

Administration, Oral↗

The experience of living with persistent pain.

This article reports themes from a descriptive exploratory study conducted with 17 persons who live with persistent pain. The purpose of the research was to enhance understanding of what it is like to live with persistent pain from the perspectives of those who live the experience. Participant narratives of living with persistent pain included descriptions of physical pain as well as the pain of loss and restriction. The theory of human becoming provided the framework for guiding researcher-participant discussions and interpretation of findings. Three themes arose from the analysis: forbearance surfaces with the drain of persistent anguish; isolating retreats coexist with comforting engagements; and hope for relief clarifies priorities for daily living. The findings expand understanding about quality of life for persons who live with persistent pain. They also challenge nurses to begin focusing on the person who lives with pain as the messenger of how to endure. Recommendations, based on new understanding, are offered for practice and additional research.

Activities of Daily Living↗

Expression of Chlamydia trachomatis genes encoding products required for DNA synthesis and cell division during active versus persistent infection.

During persistent infection, the intracellular bacterial pathogen Chlamydia trachomatis is viable but severely attenuates the production of new, infectious elementary bodies (EBs). To investigate the reasons for this lack of new EB output, we analysed the expression of chlamydial genes encoding products required for DNA replication and cell division, using in vitro models of active versus persistent infection and synovial tissue samples from patients with chronic Chlamydia-associated arthritis. Hep-2 cells were infected with K serovar C. trachomatis and harvested at t = 0-48 h post-infection (p.i; active). Human monocytes were infected similarly and harvested at t = 1-7 days p.i. (persistent). RNA preparations from infected/uninfected cells and patient samples were subjected to reverse transcription-polymerase chain reaction (RT-PCR) targeting polA, dnaA, mutS and parB mRNA, related to chlamydial DNA replication/segregation; these were expressed in infected Hep-2 cells from 11 to 48 h p.i; ftsK and ftsW, related to cell division, were expressed similarly. Real-time PCR analyses demonstrated that significant accumulation of chlamydial chromosome began at about 12 h p.i. in infected Hep-2 cells. In infected human monocytes, polA, dnaA, mutS and parB mRNA were produced from days 1-7 p.i. and were weakly expressed in patient samples. Real-time PCR indicated the continuing accumulation of chlamydial chromosome during the 7 day monocyte infection, although the rate of such accumulation was lower than that occurring during active growth. However, transcripts from ftsK and ftsW were detected only at 1 day p.i. in infected monocytes but not thereafter, and they were absent in all patient samples. Thus, genes whose products are required for chlamydial DNA replication are expressed during persistence, but transcription of genes whose products are required for cytokinesis is severely downregulated. These data explain, at least in part, the observed attenuation of new EB production during chlamydial persistence.

Bacterial Proteins↗

Lead exposure and cognitive development: persistence and a dynamic pattern.

OBJECTIVES: Although enormous effort has been focused over the past two decades on examining the potential adverse effects of exposure to environmental lead on human health, there has been a debate over the persistence and dynamic pattern of these effects. METHODOLOGY: Articles relevant to this issue which were published between January 1982 and December 1996 were retrieved from Medline and adjunct searching methods (i.e. hand searching of key journals, review of the bibliographies of reports known to be relevant, consulting with experts, and use of Science Citation Index). RESULTS: Currently available epidemiological evidence suggests that 'low' level exposure to lead in early childhood is likely to cause a moderate but real and detectable effect on cognitive development, and this effect appears to persist into later childhood. The findings from four long-term prospective studies seem to support the constant decrement model which assumes that cognitive deficits resulting from early lead exposure persist over an extended period of time even when exposure decreases. CONCLUSION: From a public health perspective, it is highly desirable and prudent to reduce the dispersive uses of lead. Since lead is ubiquitous and persistent in the environment and may have a subtle and persistent effect on cognitive development, how to set the environmental standards for lead exposure is an important scientific issue still open for debate.

Child↗

Persistent right umbilical vein: incidence and significance.

OBJECTIVES: To conduct a prospective evaluation of the incidence and neonatal outcome of fetuses with persistent right umbilical vein. This condition had traditionally been considered to be extremely rare and to be associated with a very poor neonatal prognosis, but later evidence has raised some doubts about the veracity of these contentions. METHODS: Between August 1995 and November 1998, 8950 low-risk patients were prospectively evaluated at two medical centers. The sonographic diagnosis of a persistent right umbilical vein was made in a transverse section of the fetal abdomen when the portal vein was curved toward the stomach, and the fetal gall bladder was located medially to the umbilical vein. RESULTS: Persistent right umbilical vein was detected in 17 fetuses during the study. Four of them had additional malformations, of which three had been detected antenatally. CONCLUSIONS: We established that the incidence of persistent right umbilical vein in a low-risk population is 1 : 526. We believe that the sonographic finding of this anomaly is an indication for conducting targeted fetal sonography and echocardiography. When the persistent right umbilical vein is connected to the portal system and other anomalies are ruled out, the prognosis can generally be expected to be favorable.

Congenital Abnormalities↗

Endothelin system in human persistent and paroxysmal atrial fibrillation.

INTRODUCTION: Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease. METHODS AND RESULTS: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 controls in sinus rhythm. The mRNA amounts of pro-endothelin-1 (pro-ET-1), endothelin receptor A (ET-A), and endothelin receptor B (ET-B) were studied by semiquantitative polymerase chain reaction. Protein amounts of the receptors were investigated by slot-blot analysis. mRNA amounts of pro-ET-1 were increased (+40%; P = 0.002) only in AF patients with underlying valve disease. ET-A and ET-B receptor protein amounts were significantly reduced in patients with paroxysmal AF (-39% and -47%, respectively) and persistent AF with underlying valve disease (-28% and -30%, respectively) and in persistent AF without valve disease (-20% and -40%, respectively). ET-A mRNA expression was unaltered in paroxysmal and persistent AF, whereas ET-B mRNA was reduced by 30% in persistent AF with (P < 0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF. CONCLUSION: Substantial changes in gene expression of the endothelin system were observed in human atria during AF, especially in the presence of underlying valve disease. Alterations in endothelin expression associated with AF could play a role in the pathophysiology of AF and the progression of underlying heart disease.

Aged↗

Prognostic factors for persistent distal renal tubular acidosis after surgery for posterior urethral valve.

Risk factors, including age at presentation, age at surgery, time between presentation and surgery, urodynamic abnormalities, and vesicoureteric reflux, were prospectively studied for the development of distal renal tubular acidosis (DRTA) before surgery and persistent DRTA after surgery in 24 boys with posterior urethral valve (PUV) with normal serum creatinine levels. DRTA was persistent in 11 of 17 boys (65%) at the end of follow-up after intervention. For the development of DRTA before surgery, only a longer time between presentation and surgery (intervening period) turned out to be a significant risk factor on multivariate analysis (beta = -0.13; P = 0.04). Boys with persistent DRTA after surgery had older age at presentation (P = 0.03), older age at surgery (P = 0.001), a longer intervening period (P = 0.0007), and bilateral or severe unilateral reflux (P = 0.04) before surgery. On univariate logistic regression, age at surgery (beta = -0.07; P = 0.04) and intervening period (beta = -0.13; P = 0.02) were found to be significant risk factors for persistent DRTA, but on multivariate analysis, only intervening period was found to be significant (beta = -0.13; P = 0.02). A delay in intervention after noticing voiding symptoms can predict a high incidence of DRTA before intervention and persistent DRTA after surgery in boys with PUV.

Acidosis, Renal Tubular↗

Management of children with infection-associated persistent diarrhea.

Diarrhea is the leading cause of death in children younger than 5 years of age; persistent diarrhea accounts for 30 to 50 percent of those deaths in developing countries. Malnutrition, immunosuppression, young age, and an increase in the preceding diarrhea burdens are risk factors for the development of persistent diarrhea. Although many viruses, bacteria, and parasites can produce persistent diarrhea, enteropathogenic Escherichia coli , enteroaggregative E. coli, Giardia, Cryptosporidium , and Cyclospora are the most important of these agents. With currently available tests, identifying a specific cause usually is difficult. Newer sensitive molecular tests must be used for studying the epidemiology of persistent diarrhea in children. Management includes rehydration, adequate diet, micronutrient supplementation, and antimicrobials. Persistent diarrhea seriously affects nutritional status, growth, and intellectual function. Meeting these challenges is profoundly important, particularly in developing countries.

Anti-Infective Agents↗

Previous injuries and persisting symptoms in female soccer players.

One hundred and fifty players in a female senior soccer division, starting up a new season, were examined for past injuries and persisting symptoms. An incidence of 0.18 injury/player/year was found, which is not significantly different from previously reported injury rates for male soccer. Sprains to the lower extremity and shin-splints were the most common previous injuries. Forty-three percent of the players had some kind of persistent symptom as a result of a past injury. Symptoms from previous ankle and knee sprains and from overuse injuries were the most common. Players who had sustained an ankle joint injury were more prone to have persistent symptoms (p less than 0.05) if they had persistent mechanical instability. Compared to previous retrospective studies on men's soccer, the women showed a higher rate of previous patellar dislocations. These injuries often caused persistent symptoms. The women showed fewer serious knee injuries. This might depend on a real difference in incidence or is just a reflection of female players ceasing to play soccer after a severe knee injury.

Adolescent↗

[Therapy of persistent erosion after severe chemical eye burn with the excimer laser].

BACKGROUND: The course after severe eye burns is characterized by many complications which require a longlasting and intensive therapy. The success of treatment is menaced especially by superficial problems like persistent erosiones which occur also after keratoplasty. PATIENT: As a cause of persistent erosions, pathological changes of Bowmans' membrane are discussed. Therefore, it was removed by PTK (phototherapeutic keratectomy) in our patient, in order to allow better adhesion of the epithelium to the deeper, less changed layers. THERAPY AND OUTCOME: The patient suffered from a severe burn accident of his right eye with liquid cement. After proliferations were excised twice, we had to glue on a hard contact lens as an artificial epithelium due to a persistent erosion. Later, the development of a bacterial keratitis required keratoplasty. The epithelium remained intact for eleven months, but then an erosion arose and persisted for nine months. Therefore we performed a PTK and the epithelium closed subsequently within four days. CONCLUSION: The treatment of persistent erosions has been very difficult so far, and often procedures like artificial epithelium or even keratoplasty have been necessary. The astonishing course of our patient indicates, that PTK is a promising and less invasive therapy in these cases.

Adult↗

Persistence of middle-ear effusion after acute otitis media in children.

We observed the frequent occurrence of persistent middle-ear effusion in children with acute otitis media and followed them according to standard procedures for otologic diagnosis. We performed a life-table analysis to identify risk factors for such persistent disease. Sixty-two patients were free of middle-ear effusion at one or more clinic visits two to 13 weeks after presentation and were considered cured; 45 had effusion at all clinic visits during this period and were defined as having persistent effusion. The life-table analysis showed that the relative risk for persistence was 3.8 times higher in children less than 24 months of age as compared with children 24 months of age or older (P less than 0.001) and that this risk was 2.8 times greater for white as compared with black children (P less than 0.01). Other factors examined were not identified as significant risk factors. Persistent middle-ear effusion may be associated with impaired hearing and appears to be the most important sequela of otitis media.

Acute Disease↗

Persistent parasitemia after acute babesiosis.

BACKGROUND: Babesiosis, a zoonosis caused by the protozoan Babesia microti, is usually not treated when the symptoms are mild, because the parasitemia appears to be transient. However, the microscopical methods used to diagnose this infection are insensitive, and few infected people have been followed longitudinally. We compared the duration of parasitemia in people who had received specific antibabesial therapy with that in silently infected people who had not been treated. METHODS: Forty-six babesia-infected subjects were identified from 1991 through 1996 in a prospective, community-based study designed to detect episodes of illness and of seroconversion among the residents of southeastern Connecticut and Block Island, Rhode Island. Subjects with acute babesial illness were monitored every 3 months for up to 27 months by means of thin blood smears, Bab. microti polymerase-chain-reaction assays, serologic tests, and questionnaires. RESULTS: Babesial DNA persisted in the blood for a mean of 82 days in 24 infected subjects without specific symptoms who received no specific therapy. Babesial DNA persisted for 16 days in 22 acutely ill subjects who received clindamycin and quinine therapy (P=0.03), of whom 9 had side effects from the treatment. Among the subjects who did not receive specific therapy, symptoms of babesiosis persisted for a mean of 114 days in five subjects with babesial DNA present for 3 or more months and for only 15 days in seven others in whom the DNA was detectable for less than 3 months (P<0.05); one subject had recrudescent disease after two years. CONCLUSIONS: When left untreated, silent babesial infection may persist for months or even years. Although treatment with clindamycin and quinine reduces the duration of parasitemia, infection may still persist and recrudesce and side effects are common. Improved treatments are needed.

Animals↗

Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection.

BACKGROUND: Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission. METHODS: We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment. RESULTS: Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner. CONCLUSIONS: Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection.

Adult↗

B-cell epitopes as a screening instrument for persistent cow's milk allergy.

BACKGROUND: Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE-binding epitopes of all 6 major cow's milk proteins (alpha(s1)-, alpha(s2)-, beta-, and kappa-casein; alpha-lactalbumin; and beta-lactoglobulin) and had some evidence suggesting that IgE antibodies from patients with persistent cow's milk allergy (CMA) recognize different epitopes on cow's milk proteins than do those from patients who were likely to outgrow their allergy. OBJECTIVE: In this study we sought to assess whether recognition of IgE antibodies of certain epitopes of cow's milk proteins would clearly separate the patients with life-long CMA from those who will become clinically tolerant to cow's milk. METHODS: According to the known IgE-binding regions of cow's milk proteins, 25 decapeptides of alpha(s1)-casein, alpha(s2)-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin, comprising the core epitopes, were synthesized on a cellulose-derivatized membrane. Sera from 10 patients with persistent CMA and 10 patients who subsequently outgrew their milk allergy were used to investigate the differences in epitope recognition. RESULTS: Five IgE-binding epitopes (2 on alpha(s1)-casein, 1 on alpha(s2)-casein, and 2 on kappa-casein) were not recognized by any of the patients with transient CMA but showed binding by the majority of the patients with persistent allergy. The presence of IgE antibodies against at least 1 of 3 epitopes (amino acid [AA] 123-132 on alpha(s1)-casein, AA 171-180 on alpha(s2)-casein, and AA 155-164 on kappa-casein) identified all patients with persistent CMA. CONCLUSIONS: The presence of IgE antibodies to distinct allergenic epitopes of cow's milk proteins can be used as a marker of persistent CMA. Prospective studies are needed to investigate the usefulness of these informative epitopes in predicting life-long CMA in young children.

Adolescent↗