bluuebunny/crossref_metadata_2025 huggingface dataset:
Receiver operating characteristic curve analysis of cutaneous skin test reactions to predict hay fever and asthma symptoms in the Normative Aging Study
Authors: Weintraub J. M. , Sparrow D. , Weiss S. T.
Published: March 2003

Background:  We used receiver operating characteristic (ROC) curves to determine optimal cutoff values and to evaluate the ability of ragweed, mixed grasses, mixed trees, and house‐dust antigens to predict symptoms of hay fever and asthma.

Methods:  Between 1984 and 1993, 1386 members of the Normative Aging Study cohort had at least one examination that included evaluation of cutaneous hypersensitivity to common aeroallergens by skin prick testing. Standard questionnaires based on the American Thoracic Society DLD‐78 questionnaire obtained information on respiratory symptoms, illness, and smoking habits.

Results:  Ragweed was the best univariate predictor for both hay fever and asthma symptoms: the area under the ROC curve for hay fever was 0.71 (95% CI 0.67–0.74); for asthma, it was 0.65 (95% CI 0.55–0.75). For hay fever, dichotomizing the average reaction to four antigens at 2 mm gave a sensitivity of 56% and a specificity of 83%; at 3 mm, the sensitivity was 38% and specificity 92%. For asthma, dichotomizing the skin test reaction at 2 mm gave a sensitivity ranging from 30% for reaction to mixed grasses to 56% for the ragweed antigen reaction.

Conclusions:  Although in this older population skin test reactivities did not predict current asthma symptoms with high sensitivity, our results support the use of cutoff values of 2 or 3 mm as commonly used in studies of hay fever symptoms.
A prospective study of the relationship between exposure and specific antibodies in workers exposed to organic acid anhydrides
Authors: Welinder H. , Nielsen J. , Rylander L. , Ståhlbom B.
Published: March 2003

Background: The exposure–response relationships for the induction of specific IgE and IgG were evaluated in a prospective study of workers exposed to organic acid anhydrides (OAAs). Special attention was paid to the modifying effects of atopy and smoking.

Methods: The subjects were 163 previously unexposed persons exposed to epoxy resins with hexahydro‐, methylhexahydro‐, and methyltetrahydrophthalic anhydride as curing agents. The levels of OAAs in air and of specific IgE and IgG in serum were recurrently monitored. The mean observation time was 32 (1–105) months.

Results: The mean combined OAA exposure of the subjects was 15.4 (<1–189) μg/m3. Positive specific IgE was demonstrated by 21 (13%) subjects with a mean induction time of 8.8 (1–35) months. The incidence of sensitization was 4.1 cases/1000 months at risk. The relative risk (OR) for atopics was 5.4 (1.9‐15.3; 95% CI). An exposure–response relationship was demonstrated by an increasing risk of sensitization with increasing exposure.

Conclusions: An association between exposure and atopy, respectively, and the induction of specific antibodies against OAAs were observed. The risk for atopics was comparable with the risk for the subjects in the most exposed group.
The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen
Authors: Martínez A. , Asturias J. A. , Monteseirín J. , Moreno V. , García‐Cubillana A. , Hernández M. , De La Calle A. , Sánchez‐Hernández C. , Pérez‐Formoso J. L. , Conde J.
Published: March 2003

Many works have dealt with the study of the allergenic relevance of profilin from allergenic extracts, mainly derived from pollens and vegetable foods. Olive pollen extracts also contain a profilin allergen (Ole e 2). This protein has been characterized in detail, so the aminoacid sequence of three isoforms and the structural model of one of them are already known. The prevalence of Ole e 2 for olive allergenic patients has been evaluated by different in vivo and in vitro methods, and the results compared with those obtained for another pollen profilins.
Features and severity of occupational asthma upon diagnosis: an Italian multicentric case review
Authors: Moscato G. , Dellabianca A. , Maestrelli P. , Paggiaro P. , Romano C. , De Zotti R. , Marabini A. , Voltolini S. , Crippa M. , Previdi M. , Bramé B. , Benzon R. , Siracusa A.
Published: March 2003

Background. The severity of occupational asthma (OA) at the time of diagnosis is not known. In this study we aimed to evaluate some features of the disease at the time of diagnosis, particularly looking at severity and treatment before diagnosis.

Methods: Medical records of subjects (n = 197) who had received a diagnosis of OA in six specialized centres of Northern and Central Italy in the period 1992–97 were reviewed. The severity of the disease at the time of diagnosis was determined on the basis of symptoms, peak expiratory flow (PEF, percentage predicted), forced expiratory volume in one second (FEV1, percentage predicted), and PEF variability, following the criteria of the National Institutes of Health and World Health Organizaton (NIH/WHO) guidelines on asthma. Medications used in the month before diagnosis were recorded.

Results: The most common etiological agents were isocyanates (41.6%), flours (19.8%), woods (9.7%) and natural rubber latex (7.6%). The level of asthma severity (AS) was mild intermittent in 23.9% patients, mild persistent in 28.9%, moderate in 41.6%, and severe in 5.6%. Asthma severity was positively associated with current or previous smoking (P < 0.05), and was not related to atopy and current exposure. A relationship with bronchial reactivity to methacholine was shown in subjects at work. Treatment before diagnosis was consistent with the NIH/WHO guidelines in only 13.2% patients, whereas 75.6% were undertreated and 11.2% were overtreated.

Conclusions: In this study we found that the majority of patients had mild asthma at the time of diagnosis and that cigarette smoking was associated with a greater severity. Moreover, the majority of patients were undertreated before etiological diagnosis.
Occupational rhinoconjunctivitis and asthma in a wool worker caused by Dermestidae spp.
Authors: Brito F. Feo , Mur P. , Barber D. , Lombardero M. , Galindo P. A. , Gómez E. , Borja J.
Published: March 2003

Background: The family Dermestidae belongs to the order Coleoptera. Occupational allergy has been described in museum personnel. A 31‐year‐old male wool worker presenting rhinoconjunctivitis and asthma episodes probably linked to exposure to Dermestidae‐infected wool was investigated.

Methods: Extracts prepared either from insect bodies or from dust from parasitized wool were used for skin prick testing (SPT), conjunctival and bronchial provocation tests and in vitro determinations.

Results: SPT and provocation tests were positive to both extracts. PEFR measurement demonstrated the association between the patient's symptoms and occupational exposure to Dermestidae. Specific IgE to both extracts was detected and immunoblotting revealed several protein bands from 5 to 200 kDa that were reactive to IgE from the patient's serum.

Conclusions: Dermestidae exposure in wool workers when handling parasitized wool can be a cause of IgE‐mediated rhinoconjunctivitis and asthma.
Circulating Interleukin 16 (IL‐16) in children with atopic/eczema dermatitis syndrome (AEDS): a novel serological marker of disease activity
Authors: Frezzolini A. , Paradisi M. , Zaffiro A. , Provini A. , Cadoni S. , Ruffelli M. , De Pità O.
Published: March 2003

Background: Chemokines play a central role in atopic eczema/dermatitis syndrome (AEDS). Interleukin 16 (IL‐16) has been described as a main cytokine involved in CD4+ cell recruitment during inflammation. Recently the influx of CD4+ lymphocytes has been related to the up‐regulation of IL‐16 in AEDS skin lesions. Circulating β‐chemokines (Eotaxin and RANTES) and IL‐16 were investigated in children with AEDS to correlate their presence with the severity of the disease. We also measured serum levels of soluble CD30 (sCD30), a marker of Th2 immune responses related to AEDS disease activity.

Methods: Serum levels of eotaxin, RANTES, IL‐16 and sCD30 were measured by immunoenzymatic assay in paediatric patients with pure AEDS (pAEDS, n = 39); the severity of the disease was graded by SCORAD. Fifteen children with AEDS in presence of respiratory allergy (AEDS+A), 15 with allergic asthma (A) and 20 age‐matched healthy donors were investigated as control groups.

Results: When compared to normals, high amounts of Eotaxin and IL‐16 were detected in sera of pAEDS (P = 0.002; P < 0.0001), AEDS+A (P = 0.02; P = 0.01) and A patients (P = 0.004; P = 0.03) with respect to normals. Serum levels of RANTES were also elevated in pAEDS patients, significantly higher than normals (P = 0.009), whereas no statistically significant differences could be detected between pAEDS and AEDS+A or A groups. IL‐16 was progressively increased in the different stages of pAEDS, with a positive correlation between IL‐16 and both SCORAD and sCD30 (P < 0.0001).

Conclusion: We suggest that IL‐16 could serve as a useful marker of disease activity in childhood pAEDS.
In allergic asthma experimental exposure to allergens is associated with depletion of blood eosinophils overexpressing LFA‐1
Authors: Lantero S. , Spallarossa D. , Silvestri M. , Sabatini F. , Scarso L. , Crimi E. , Rossi G. A.
Published: March 2003

Background: In atopic individuals, exposure to allergens is followed by recruitment of blood eosinophils in the target tissue. We investigated whether allergen inhalation challenge could result in depletion of blood eosinophils overexpressing adhesion molecules involved in eosinophil migration.

Methods: Blood eosinophils were isolated from seven atopic asthmatic patients and seven control subjects and the “at baseline” expression of lymphocyte function‐associated antigen‐1 (LFA‐1), macrophage antigen‐1 (Mac‐1) and very late antigen‐4 (VLA‐4) was assessed by monoclonal antibody staining and flow cytometry analysis. Asthmatic patients underwent allergen challenge and the expression of LFA‐1, Mac‐1 and VLA‐4 by blood eosinophils was again evaluated 3 h and 24 h after allergen challenge.

Results: As compared to controls, eosinophils from atopics showed at baseline enhanced LFA‐1 expression (P=0.0012), but similar Mac‐1 or VLA‐4 expression (P > 0.1, each comparison). In atopics, the percentage and absolute number of blood eosinophils were significantly decreased 3 h after allergen challenge (P=0.001 and P=0.022, respectively) but returned to similar values to prechallenge values after an additional 21 h (P > 0.1). Allergen challenge was also followed by a significant decrease in LFA‐1 expression by eosinophils, at 3 h (P=0.002) and at 24 h (P=0.038), while no changes in Mac‐1 and VLA‐4 were observed. A significant correlation between postchallenge decrease in LFA‐1 expression and in blood eosinophilia, both expressed as percentage (r=0.88; P < 0.01) or absolute number (r=0.87; P < 0.01) was demonstrated at 3 h (r=0.88; P < 0.01) but not at 24 h (r=0.64, P > 0.05 and r=0.11; P > 0.05, respectively).

Conclusion: In allergic asthma, an early recruitment of blood eosinophils overexpressing LFA‐1 occurs in the first hours after allergen challenge.
Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics
Authors: Chew G. L. , Rogers C. , Burge H. A. , Muilenberg M. L. , Gold D. R.
Published: March 2003

Background: Exposure to fungi is often assessed by culturing floor dust or air samples. Our objective was to evaluate the relationships between dustborne and airborne fungi and to identify factors that modify these relationships.

Methods: From November 1994 to September 1996 sequential duplicate 45‐l air samples were collected in bedrooms of 496 homes in the Boston area, using a Burkard culture plate sampler. After air sampling, bedroom floors were sampled with a vacuum cleaner that was modified to collect dust in a cellulose extraction thimble. Dust was sieved, and the fine dust was dilution‐plated onto DG‐18 media.

Results: Concentrations of total culturable fungi per gram of bedroom‐floor dust were correlated weakly, but significantly, with those of indoor air (r = 0.13, P < 0.05). Concentrations of some individual taxa in the dust and indoor air were also weakly associated. Adjusting for the concentrations of fungi in outdoor air, dustborne fungal concentrations were positively associated with those in indoor air for the taxa Cladosporium and Penicillium, but not for total fungi. The indoor air fungal levels were often predicted by different covariates to those predicting fungal levels in dust. The type of housing (house or apartment) and the presence of carpeting were often predictive factors for dust fungi. In contrast, outdoor fungal levels were often predictive of the indoor air fungal levels.

Conclusions: Because our data do not indicate a strong overall relationship between culturable fungi in dust and indoor air, the results from these two methods (dust and air sampling) likely represent different types of potential fungal exposures to residents. It may be essential to collect both air and dust samples, as well as information on housing characteristics, as indicators for fungal exposure.
Beef allergy: a review of 12 cases
Authors: Orhan F. , Sekerel B. E.
Published: March 2003

Background: Although beef allergy has long been considered a rare condition, the number of studies regarding the nature, epidemiology, and symptoms of beef allergy has been increasing. We aimed to describe the results of allergy work‐up of 12 patients who have a convincing history of acute allergic symptoms following beef ingestion.

Methods: Detailed histories of 10 children and two adult relatives were obtained and patients underwent skin prick tests with commercial beef extract, raw beef and cooked beef. Serum total and beef‐specific IgE were measured. Labial, and in selected cases, open food challenges were undertaken.

Results: Interestingly, the rate of family history of beef allergy was 67% (8/12). Three patients (two with commercial extract, and one with cooked beef) had positive skin test responses to beef. Ten (83%) patients had elevated serum IgE concentrations (median 316.5 kU/l, range 9–1321 kU/l) and the beef‐specific IgE was positive in all patients (median 6.23 kUA/l, range 0.83–36.6 kUA/l). Labial food challenge was positive in four (30%) patients. Of the five patients who underwent open food challenges, three were positive and two tolerated the beef administered.

Conclusions: We conclude that skin prick tests do not accurately diagnose IgE‐mediated sensitization to beef. Thus, patients with suspected beef allergy should be screened additionally for beef‐specific IgE antibodies, and in selected cases oral food challenge should be carried out to verify the diagnosis.
Introduction to nasal and pulmonary allergy cascade
Authors: Canonica G. W.
Published: March 2003

The early phase of an IgE‐dependent allergic reaction is followed by the activation of a complex network of inflammatory phenomena – T lymphocytes, cytokines, mediators, and adhesion molecules – that mediate late and ongoing allergic symptoms. The kinetics of respiratory inflammation following allergen exposure involve the migration of inflammatory cells to the mucosa within about 30 min, increased inflammatory infiltration over the following hours, and then slow subsidence. A relationship between asthma and allergic rhinitis is supported by epidemiological, histological, physiological, and immunopathological data, and by the response of asthma symptoms in rhinitic patients to intranasal corticosteroids and antihistamines. For example, there is no morphological difference between the bronchial inflammatory response following allergen‐specific challenge in patients suffering from asthma alone or rhinitis alone. It is the allergen dose that makes the difference in the airway response to allergen in allergic rhinitis and asthma. Recognition of the relationship between asthma and allergic rhinitis has led to the introduction of new diagnostic terminology and treatment recommendations: 1) patients with persistent rhinitis should be evaluated for asthma; 2) patients with persistent asthma should be evaluated for rhinitis; and 3) a strategy should combine the treatment of upper and lower airways in terms of efficacy and safety.
Identification and characterization of ade novopartial trisomy 10p by comparative genomic hybridization (CGH)
Authors: Benzacken B. , Lapierre JM , Siffroi JP , Chalvon A. , Tachdjian G.
Published: March 2003

We report the characterization of ade novounbalanced chromosome rearrangement by comparative genomic hybridization (CGH) in a 15‐day‐old child with hypotonia and dysmorphia. We describe the combined use of CGH and fluorescencein situhybridization (FISH) to identify the origin of the additional chromosomal material on the short arm of chromosome 6. Investigation with FISH revealed that the excess material was not derived from chromosome 6. Identification of unknown unbalanced aberrations that could not be identified by traditional cytogenetics procedures is possible by CGH analysis. Visual analysis of digital images from CGH‐metaphase spreads revealed a predominantly green signal on the telomeric region of chromosome 10p. After quantitative digital ratio imaging of 10 CGH‐metaphase spreads, a region of gain was found in the chromosome band 10p14‐pter. The CGH finding was confirmed by FISH analysis, using a whole chromosome 10 paint probe. These results show the usefulness of CGH for a rapid characterization ofde novounbalanced translocation, unidentifiable by karyotype alone.
Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome
Authors: Roifman Chaim M
Published: March 2003

The clinical and laboratory combination of recurrent infections due to antibody deficiency, spondyloepiphyseal dysplasia, growth retardation and retinal dystrophy is novel. Four patients with strikingly similar phenotypes from three different families of diverse genetic backgrounds are described, suggesting a similar underlying genotype. Increased awareness of this syndrome will hopefully lead to the description of a larger number of affected individuals, which ultimately might be critical for its genetic characterization.
Linkage disequilibrium mapping of the Nova Scotia variant of Niemann–Pick disease
Authors: Greer WL , Riddell DC , Murty S , Gillan TL , Girouard GS , Sparrow SM , Tatlidil C , Dobson MJ , Neumann PE
Published: March 2003

Niemann–Pick type D (NPD) disease is a severe degenerative disorder of the nervous system characterized by the accumulation of tissue cholesterol and sphingomyelin. Because of a founder effect, it is unusually common in southwestern Nova Scotia, Canada. We have confirmed that almost all patients from 20 affected sibships descended on both sides from a small group of Acadians who settled in this region in about the year 1767. Previously using classic linkage analysis of this large kindred, we defined the critical gene region to a 13‐cM chromosome segment between D18S869 and D18S66. Seven ESTs have been positioned within this interval. Carstea et al. (Niemann–Pick C disease gene: homology to mediators of cholesterol homeostasis. Science 1997: 277: 232–235) recently demonstrated that one of these ESTs is the Niemann–Pick type C (NPC1) gene, the gene disrupted in most patients with NPC disease, and we have shown that a G3097→T mutation in the NPC1 gene is also responsible for NPD. Here we report the development of five new polymorphic microsatellite markers and the testing for complete linkage disequilibrium in our single large NPD kindred that allowed us to reduce the NPD critical region to a 1‐cM (1.3–1.6 Mb) interval between D18S1398 and D18S1108. In contrast, Carstea et al., using classic linkage analysis, required more than 18 unrelated NPC families to reduce the NPC1 critical region to a 5‐cM interval. Our work supports the finding that NPD is an allelic variant of NPC1, and illustrates the power of large kindreds, which are common in Atlantic Canada and other relatively isolated areas, for gene mapping and identification.
Pure trisomy 10p involving an isochromosome 10p
Authors: Berend Sue Ann , Shaffer Lisa G , Bejjani Bassem A
Published: March 2003

We report a child with trisomy 10p due to a translocation of the long arm of chromosome 10 to the short arm of chromosome 14 and isochromosome formation of 10p [46,XX,i(10)(p10),der(14)t(10;14)(q10;p10)]. Most reported cases of trisomy 10p involve double segmental imbalance. In contrast, the clinical features described in the current case represent pure trisomy 10p and, thus, delineate the 10p trisomy syndrome phenotype. Mechanisms of the chromosomal rearrangements in this case are suggested.
Angelman syndrome with uniparental disomy due to paternal meiosis II nondisjunction
Authors: Gyftodimou J , Karadima G , Pandelia E , Vassilopoulos D , Petersen Mb
Published: March 2003

We report a case of Angelman syndrome (AS) with paternal uniparental disomy (pUPD) of chromosome 15. This 6‐year‐old girl with overgrowth had frequent, but only provoked laughter, was mildly ataxic with limb hypertonia, and had no intelligible speech. She had deep‐set eyes, protruding tongue, and prominent chin. The karyotype was normal. DNA analysis with microsatellites from chromosome 15 showed no inheritance of maternal alleles both within and outside the AS critical region. Proximal markers showed reduction to homozygosity of paternal alleles, intermediate markers showed nonreduction, and distal markers reduction, thus suggesting a meiosis II nondisjunction event in the father with two crossovers. This is, to our knowledge, the first reported case of AS due to meiosis II nondisjunction. We present detailed physical measurements in this patient, adding to the clinical description of the milder phenotype in AS due to pUPD.
Aberrant SP‐B mRNA in lung tissue of patients with congenital alveolar proteinosis (CAP)
Authors: Lin Z , DeMello De , Batanian Jr , Khammash Hm , DiAngelo S , Luo J , Floros J
Published: March 2003

Mutations in the surfactant protein (SP)‐B gene are responsible for SP‐B deficiency in congenital alveolar proteinosis (CAP) (Nogee et al. J Clin Invest 1994: 93: 1860–1883; Lin et al. Mol Genet Metab 1998: 64: 25–35; Klein et al. Pediatrics 1998: 132: 244–248; Ballard et al. Pediatrics 1995: 96: 1046–1052). The multigenerational consanguineous pedigree under study does not carry any of the known mutations, although this pedigree had 14 infant deaths following respiratory distress at birth. Immunostaining of the lungs from three such infants revealed decreased or absent SP‐B. By sequencing of SP‐B exons, exon–intron junctions, and the 5′ and 3′ flanking regions, nine polymorphisms were found in this pedigree, but none of them could explain the observed SP‐B deficiency. Further analysis of SP‐B mRNA by reverse transcription‐polymerase chain reaction from paraffin‐embedded lung tissue of CAP patients showed that SP‐B mRNA is not intact. Although the sequence of mRNA from exon 1–exon 7 and from exon 8–exon 10 could be amplified, the region between exons 7 and 8 could not. From fluorescence in situ hybridization of the short arm of chromosome 2p, only 2 signals were identified, eliminating the possibility of translocation as the cause of the SP‐B mRNA aberrance. Although the nature of the genetic basis of SP‐B deficiency in this family is currently unknown, the existence of aberrant SP‐B mRNA may, at least in part, be responsible for the SP‐B deficiency in this pedigree.
A boy with a submicroscopic 22qter deletion, general overgrowth and features suggestive of FG syndrome
Authors: De Vries Bba , Bitner‐Glindzicz M , Knight Sjl , Tyson J , MacDermot Kd , Flint J , Malcolm S , Winter Rm
Published: March 2003

Over recent years, submicroscopic subtelomeric rearrangements have been shown to be a significant cause of mental retardation and, therefore, such abnormalities should be considered in every child with moderate to severe retardation with additional features suggestive of a chromosomal abnormality. The FG syndrome is an X‐linked recessive mental retardation syndrome with congenital hypotonia, relative macrocephaly, a characteristic facies and constipation.  We describe a severely mentally retarded boy with a history of severe constipation, truncal hypotonia, facial dysmorphism, fetal pads, and joint laxity, leading to an initial diagnosis of FG syndrome at the age of 3 years. Clinical re‐evaluation at the age of 6 years, when he showed signs of general overgrowth, initiated a telomere screen, and a submicroscopic 22q13.3 telomere deletion was detected.  The features suggestive of FG syndrome in this boy with a 22q13.3→qter deletion may indicate testing for submicroscopic 22qter deletions in patients with atypical features of FG syndrome without a definite X‐linked family history.
Segregation of a supernumerary del(15) marker chromosome in sperm
Authors: Cotter PD , Ko E , Larabell SK , Rademaker AW , Martin RH
Published: March 2003

Supernumerary marker chromosomes (SMC) can be associated with both normal and abnormal phenotypes. In addition, SMC are found at higher frequency in males with infertility. We identified a SMC, characterized as a del(15)(q11.2) chromosome, in a phenotypically normal male. Using fluorescence in situ hybridization (FISH), we examined the segregation of the del(15) chromosome in sperm from this patient. Only 6.23% of sperm nuclei showed disomy using a chromosome 15 α‐satellite FISH probe, instead of the expected 50%. In addition, FISH analysis showed no increase for non‐disjunction of chromosome 18, excluding an interchromosomal effect for this chromosome. The significant decrease in sperm bearing the del(15) may be due to tissue‐specific mosaicism or a result of some form of selection against the del(15) during spermatogenesis. This finding provides a basis for the observation that SMC(15) are less likely to be inherited from a paternal carrier.
Living with Marfan syndrome I. Perceptions of the condition
Authors: Peters KF , Kong F , Horne R , Francomano CA , Biesecker BB
Published: March 2003

We present data from an exploratory study of 174 adults with Marfan syndrome regarding their cognitive perceptions of the condition as postulated by the self‐regulatory model (Leventhal H, Benyamini Y, Brownlee S et al. In: Petrie KI, Weinman JA, eds. Perceptions of Health and Illness: Current Research and Applications. Amsterdam, The Netherlands: Harwood Academic, 1997: 19–45; Leventhal H, Nerenz DR, Steele DJ. In: Baum A, Taylor SE, Singer JE, eds. Handbook of Psychology and Health. Hillsdale, NJ: Lawrence Erlbaum Associates, 1984: 219–252). The vast majority of the respondents had adequate general knowledge about Marfan syndrome. Eighty‐three percent of the respondents perceived Marfan syndrome as having had significant adverse consequences on their lives. Having striae, pain (sore joints), and depression were each independently correlated with this view. Fifty‐eight percent of the respondents indicated that they felt they had low to moderate control over their condition, demonstrating variability. History of aortic dissection, pain (sore joints), and depressive symptoms were each negatively correlated with the view that Marfan syndrome is a curable/controllable condition. Moreover, approximately 28% view the condition as a lethal condition, whereas 67% view it as a serious condition. Forty‐four percent of the cohort were found to have significant symptomatology of depression independent of beta‐ and Ca2+‐channel blockade use. Respondents cited both advantages and disadvantages of being affected. Genetic counseling that addresses patients’ perceptions of Marfan syndrome, and its associated pain, fatigue, and depressive symptoms, may enhance patient adaptation to the condition.
Non‐syndromic X‐linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene
Authors: Lebel RR , May M , Pouls S , Lubs HA , Stevenson RE , Schwartz CE
Published: March 2003

Three brothers with non‐syndromal X‐linked mental retardation were found to have a novel missense mutation in FGD1, the gene associated with the Aarskog syndrome. Although the brothers have short stature and small feet, they lack distinct craniofacial, skeletal or genital findings suggestive of Aarskog syndrome. Their mother, the only obligate carrier available for testing, has the FGD1 mutation. The mutation, a C934T base change in exon 4, results in the proline at position 312 to be substituted with a leucine. This missense mutation is predicted to eliminate a β‐turn, creating an extra‐long stretch of coiled sequence which may affect the orientations of an SH3 (Src homology 3) binding domain and the first structural conserved region. A new molecular defect associated with non‐syndromal X‐linked mental retardation affords an opportunity to seek specific diagnosis in males with previously unexplained developmental delays and this opens further predictive tests in families at risk.
Two novel mutations in the sterol 27‐hydroxylase gene causing cerebrotendinous xanthomatosis
Authors: Lamon‐Fava S , Schaefer EJ , Garuti R , Salen G , Calandra S
Published: March 2003

Cerebrotendinous xanthomatosis (CTX) is a rare recessive autosomal disease caused by mutations of the sterol 27‐hydroxylase gene. Clinically, CTX is characterized by tendon xanthomas, cataracts and progressive neurological deficits. Because of the disruption of the 27‐hydroxylase activity, CTX patients have elevated plasma levels of cholestanol, a by‐product of abnormal bile acid synthesis. The present authors describe a female patient with CTX. The proband in this study presented with elevated cholestanol levels, markedly reduced mitochondrial 27‐hydroxylase activity and altered bile acid composition. The 27‐hydroxylase gene was analysed for mutations by polymerase chain reaction amplification of the exons and the splice‐junction regions of the gene. The proband was found to be a compound heterozygote for two different mutations which have not been previously described: (1) a G → A transition at nucleotide 455 that is responsible for converting a glycine to a glutamic acid residue at amino acid position 112 (G112E); and (2) a five‐nucleotide deletion in exon 5 (from nucleotide 965 to 969) that is responsible for a shift in the reading frame and the insertion of a premature codon at position 296, and consequently, the synthesis of a truncated protein lacking the heme‐binding and andrenodoxin‐binding domains. Long‐term (18‐year) treatment of the proband with chenodeoxycholic acid (750 mg day−1) has been effective in preventing any progression of the disease.
Presence of the d8/17 B‐cell marker in children with rheumatic fever in Israel
Authors: Harel L , Zeharia A , Kodman Y , Straussberg R , Zabriskie JB , Amir J
Published: March 2003

A genetic predisoposition to rheumatic fever (RF) has been suspected by several researchers. Ten years ago, using monoclonal antibodies, the B‐cell alloantigen D8/17 was identified in 90–100% of patients with RF. The aim of the present study was to evaluate whether the marker is found in patients with RF in Israel, where the population is made up of diverse ethnic groups. The Schneider Children's Medical Center in Petah Tikva, Israel, was the setting for this study. The population included 22 children with RF and nine ethnically matched, disease‐free individuals who served as controls. Each of the patients and controls were tested for the B‐cell antigen with flow cytometry assay by using monoclonal antibodies. The main outcome measure was the difference in the presence of the D8/17 B‐cell marker between the patients with RF and the controls. The mean percentage of B‐cells expressing the marker was 11.5 ± 2.9 in the patients and 4.24 ± 2.7 in the controls (P < 0.001). There was no statistically significant difference in the frequency of the marker by ethnic origin. The present results support earlier studies suggesting that D8/17 is a disease‐specific marker with a world‐wide distribution which may potentially serve as an additional diagnostic tool in patients with suspected RF.
Facial clefting in an Arab town in Israel
Authors: Jaber L , Nahmani A , Halpern GJ , Shohat M
Published: March 2003

To study the prevalence of cleft palate and cleft lip with or without cleft palate in an Israeli Arab town, questionnaires were sent to the parents of 1375 pupils in grades 1 and 2 in all seven primary schools in the town of Taibe, and 1281 responded. The information requested included data about siblings and members of the parental generation to give a total of 16 174, and the presence of consanguinity and history of exposure to medication, radiation, smoking or alcohol during pregnancy.

There were four affected individuals among the index cases, of whom two had cleft palate only and two cleft lip with cleft palate, giving prevalence rates for each of these of 1.56/1000. Adding to these the number of affected siblings gave a total of 10 affected individuals; two with cleft palate only (0.39/1000) and eight with cleft lip with or without cleft palate (1.56/1000). Among the parental generation, of 16 reported affected individuals, two had cleft palate only (0.18/1000) and 14 cleft lip with or without cleft palate (1.26/1000). The overall prevalence rate for all 26 affected individuals was 1.6/1000; four of these had cleft palate only (0.24/1000) and 22 had cleft lip with or without cleft palate (1.36/1000). There were no cases whose mothers had been exposed to medication, radiation, smoking or alcohol during pregnancy. The effect of consanguinity was not significant (P < 0.92). This study shows that the prevalence of facial clefting in an Israeli Arab community is consistent with that in the general population worldwide.
Bronchomalacia associated with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries, and chromosome 22q11.2 deletion
Authors: Yamagishi H , Maeda J , Higuchi M , Katada Y , Yamagishi C , Matsuo N , Kojima Y
Published: March 2003

Respiratory distress is one of the major complications in young infants with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries (PA‐VSD‐MAPCA); however, its aetiology remains obscure. We have previously reported an association of bronchomalacia with PA‐VSD‐MAPCA in patients with a hemizygous deletion of chromosome 22q11.2 (del.22q11). To clarify the clinical relevance of bronchomalacia in patients with PA‐VSD‐MAPCA and del.22q11, we reviewed the clinical and laboratory records of four patients with PA‐VSD‐MAPCA who had del.22q11 and bronchomalacia. External bronchial compression by anomalous patterning of the aorta and MAPCA was documented in three of the four patients, using combinatorial examination of angiocardiography, bronchography, fibreoptic bronchoscopy and magnetic resonance imaging. One of the four patients died suddenly of severe respiratory distress at 4 years of age, while the remaining three were inoperable for complete surgical repair. Our study indicates that bronchomalacia as a result of external vascular compression may be an aetiology of early‐onset respiratory distress in some patients with PA‐VSD‐MAPCA and del.22q11, and can significantly affect the clinical outcome.
Diploid/triploid mosaicism in dysmorphic patients
Authors: Van De Laar I , Rabelink G , Hochstenbach R , Tuerlings J , Hoogeboom J , Giltay J
Published: March 2003

Diploid/triploid mosaicism is a dysmorphology syndrome consisting of mental retardation, truncal obesity, body and/or facial asymmetry, growth retardation, hypotonia, a small phallus, malformed low‐set ears and micrognathia. In 75% of the cases, the blood karyotype is normal and the diagnosis can only be established after analysis of cultured fibroblasts. This chromosome abnormality may therefore be underdiagnosed. This paper focuses on the identification of mentally retarded and dysmorphic patients with diploid/triploid mosaicism. Detailed clinical description of well‐defined patients may help in deciding if a skin biopsy for karyotyping of fibroblasts should be taken. Three new cases are presented, in which DNA marker analysis showed that the extra set of chromosomes in each case was derived from the mother. We present a review of 25 cases described in the literature and we discuss the inclusion of a second polar body into an early diploid embryo as the most likely mechanism.
Deciding on cadaveric organ donation in Black African families
Authors: Kometsi K , Louw J
Published: March 2003

This study explores factors that have affected the decision of Black African families to donate cadaveric organs. Semi‐structured interviews were conducted with ten families living in greater Cape Town, South Africa. Addresses were obtained from records of the transplant co‐ordinators at Groote Schuur Hospital. The data were analysed according to broad themes emerging from the interviews. The most important themes were the influence of violent, criminal deaths; the need for a longer period of consultation among family members; belief in the integrity of the ancestor's body; lack of understanding of brain death; and experiences of grief and loss.
Cytomegalovirus immune globulin after liver transplantation: a cost‐effectiveness analysis 1
Authors: Arbo Manuel Dj , Snydman David R , Wong John B , Goldberg Howard S , Schmid Christopher H , Pauker Stephen G
Published: March 2003

Objective: Cytomegalovirus (CMV) immune globulin (CMVIG) has been shown to significantly reduce severe CMV‐associated disease complicating orthotopic liver transplant (OLT). We evaluated the economic impact of severe CMV‐associated disease and calculated the marginal cost‐effectiveness (C/E) of routine prophylaxis with CMVIG after OLT.Design: C/E analysis.Setting: Four teaching hospitals in Boston.Patients: Patients who underwent OLT from January 1988 through June 1990.Measurements: We gathered actual cost data of hospital care for patients enrolled in a clinical trial of CMVIG prophylaxis in OLT. We calculated average outpatient expenses from a separate group of patients undergoing OLT and developed a regression model to estimate costs during the first year post‐transplant (R2=0.77). Based on this model, we calculated variable costs (in 1999 US dollars) for all patients in the randomized trial. From the published literature we obtained the probability of CMV outcomes and of long‐term survival after OLT. We then developed a decision analytical model to determine an incremental C/E ratio, using a Markov simulation to estimate long‐term survival and long‐term costs. We discounted costs and life‐years at 3% and 5% per yr.Results: Based on the efficacy rate of 54% in the controlled trial, we estimate that CMVIG will increase life expectancy by 0.65 discounted years at an additional cost of $11 600, providing a marginal C/E ratio of $17 900/yr life saved. Examining the confidence limits of efficacy, we estimate that CMVIG will have a marginal C/E ratio of $66 200 gained/yr at an efficacy of 11% and $14 000 gained/yr at an efficacy of 83%.Conclusion: After OLT, prophylactic CMVIG has an incremental C/E ratio comparable to that of other well‐accepted medical therapies and should be used routinely in these patients.
The use of flow cytometry for the detection of CMV‐specific antigen (pp65) in leukocytes of kidney recipients
Authors: Essa Sahar , Pacsa Alexander S , Al‐Attiyah Raja'a , El‐Shazly Amany , Raghupathy Raj , Said Tareq
Published: March 2003

Flow cytometric assay (FCA) was used to detect a cytomegalovirus (CMV) specific antigen (pp65) in CMV‐infected fibroblast cells and in leukocytes of kidney recipients. FCA distinguished clearly between the infected and non‐infected fibroblast cells. Regarding transplant patients, the FCA was positive when the number of antigenemia assay (AA) positive cells was five or more per 5×104. Moreover, the percentage of antigenemia‐positive cells by FCA correlated well with symptomatic CMV infections.
Renal transplantation for Type II diabetic patients compared with Type I diabetic patients and patients over 50 years old: a single‐center experience
Authors: Kronson Jeffrey W , Gillingham Kristen J , Sutherland David E R , Matas Arthur J
Published: March 2003

Introduction. Transplantation of renal allografts for Type II diabetic patients has become increasingly common. Like Type I diabetics and patients over age 50, Type II diabetics are in a high‐risk category for renal transplantation. Some investigators argue that the scarce resources of the valuable donor pool should not be allocated to these high‐risk, older individuals with end‐stage renal disease (ESRD) who often have significant comorbidity. We studied the outcome of renal transplantation for 90 Type II diabetics and compared it with the outcome for Type I diabetics and patients over age 50 with other primary diseases.  Methods. We conducted a retrospective review of data on all renal transplants performed at the University of Minnesota since September 1984 for Type II diabetics. We analyzed both patient and graft survival rates and compared them with the outcome for Type I diabetics and separately for all nondiabetics over age 50. We grouped recipients by donor source (living vs. cadaver) and age at transplant (<50 vs.> 50). We studied reasons for graft loss, patient death, pre‐operative morbidity, and post‐operative complications.  Results. We found that recipient age and donor source did not affect outcome. Overall 5‐yr patient survival for Type II diabetics was 61%; graft survival, 53%. Type II diabetics had significantly worse patient and graft survival than Type I diabetics and than nondiabetics over age 50. However, death‐censored graft survival was not different between these groups, suggesting little difference in immunologic graft loss.  Conclusions. Renal transplantation is a relatively safe, viable option for Type II diabetics with ESRD and significant comorbidity. Although their overall graft survival is less than for Type I diabetics and nondiabetics over age 50, the immunologic graft failure rate is the same in all three groups.
Detection of alloantibodies against non‐HLA antigens in kidney transplantation by flow cytometry
Authors: Rodrıguez Paulo C , Arroyave Inge H , Mejıa Gonzalo , Garcıa Luis F
Published: March 2003

The presence of alloantibodies against human leucocyte antigen (HLA)‐I and HLA‐II antigens has been associated with hyperacute and accelerated graft rejections. However, occasionally these rejections occur in patients without donor‐specific anti‐HLA antibodies, suggesting the presence of other antigenic complexes that are shared by the graft and other cell populations. Usually, these antibodies are not routinely studied and their role in graft rejection is poorly understood. For this reason, we tested, by flow cytometry, the presence of panel‐reactive alloantibodies (PRA) using different cell populations in 30 pre‐transplant sera of kidney graft recipients. The patients studied had or had not hyperacute and accelerated rejection episodes (HARE) and did not have alloantibodies against HLA of their specific donors. We found that IgG and IgM alloantibodies directed against HLA‐I antigens, different to the HLA‐I antigens of the specific donors, as well as IgG against endothelium/monocyte antigens, IgM against platelets, and IgM against T cells are significantly associated with HARE, independently of the percentage of PRA. Our findings suggest that the detection of antibodies by flow cytometry against non‐major histocompatibilty complex antigens may be useful as a pre‐transplant crossmatch in living related donor kidney transplants to diminish the incidence of HARE.
Presentation and outcomes for organ donation in patients with cerebral gunshot wounds
Authors: Croezen D. H. , Van Natta T. L.
Published: March 2003

This study was undertaken to examine the presentation and outcomes relative to solid organ donation in patients with fatal cerebral gunshot wounds at a level I trauma center over a 7‐year period. A retrospective chart review of patients with such wounds over the years 1993–99 was completed. Eighty (80) patients were considered potential solid organ donors. Of these, 28 (35%) became organ donors, yielding 97 transplantable organs. Ninety‐six percent presented with a GCS of less than 6. Mean SBP on presentation was 130, ranging from 48 to 225. Median time from presentation to death was 18 hours. Intravenous fluids given over the first 6 hours averaged 4.3 liters. Pressors were required in 68% of cases, blood products in 34%. Consent rate for donation was 32% when requested by a physician and 59% when requested by an organ procurement organization (OPO) co‐ordinator. No request was made in 15 cases. Patients with fatal cerebral gunshot wounds, but with solid organ donor potential, have a characteristic presentation. Those with hemodynamic stability and those whose hypotension responds promptly to treatment can be expected to have a donor potential despite their devastating brain injury. Minimal time and resources are required to support such patients. Additional organs may have been obtained if the request for donation was consistently separated from the families' notification of brain death, and if the request was initiated by an OPO coordinator rather than a physician. Further, all patients admitted with cerebral gunshot wounds and poor neurologic function should have local OPO referral, potential survival notwithstanding.
Inferior liver allograft survival from cadaveric donors >50 years of age?
Authors: Verran Deborah J , Gurkan A , Dilworth P , Painter A D , Dorney Chui S , Shun A , Koorey D , McCaughan G , Sheil Agr
Published: March 2003

The growing imbalance between the number of cadaveric organ donors and recipients has led to an increasing use of high‐risk donors as an option to expand the donor pool. The aim of this study was to evaluate our experience with the use of older liver (donor>50 yr of age) allografts.  The medical records, postreperfusion biopsies and laboratory results were reviewed of the 393 patients who underwent orthotopic liver transplantation between 1986 and 1997. The outcome of the 61 patients who received older livers (OL) was compared to that of the other 332 recipients.  Increasing use of OL was evident from 1992 onwards. Recipients of OL were older than recipients of younger livers (YL, p<0.001) and more commonly had underlying chronic viral hepatitis (CVH) or fulminant hepatic failure (p<0.05). Patient and allograft survival were only slightly less in recipients of OL versus YL (p=NS). Although postperfusion biopsies showed more damage in OL than YL allografts (p<0.05), this was not associated with increased primary graft failure.  OL allografts can be transplanted with acceptable results into recipients without the concern of early allograft loss.  Summary of Article: This report of one centre's experience with 61 recipients of older donor liver allografts identifies recipient factors that may also have a negative impact on allograft outcome. These factors include a diagnosis of either CVH or fulminant hepatic failure at the time of transplantation. Postreperfusion biopsies of older donor allografts tend to show more damage, but this is not associated with primary non‐function.