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Showing papers by "Boston Children's Hospital published in 1994"


Journal ArticleDOI
21 Oct 1994-Cell
TL;DR: It is shown that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin, and a corresponding fragment of human plasminogen has similar activity.

3,516 citations


Journal ArticleDOI
TL;DR: Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death.
Abstract: Background Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-β-thalassemias) is needed to counsel patients, target therapy, and design clinical trials. Methods We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. Results Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Amo...

2,941 citations


Journal ArticleDOI
TL;DR: In patients with cystic fibrosis, the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms, resulted in slight improvement in pulmonary function, and was well tolerated.
Abstract: Background Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick, purulent secretions, which results in recurrent, symptomatic exacerbations. The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I (rhDNase), a bioengineered copy of the human enzyme. Methods We performed a randomized, double-blind, placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function. A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as outpatients. Results One or more exacerbations occurred in 27 percent of the patients given placebo, 22 percent of those treated with rhDNase once daily, and 19 percent of those treated with rhDNase twice daily. As compared with placebo, the administration of rhDNase once daily and twice daily reduced the ...

1,392 citations


Journal ArticleDOI
TL;DR: There is sufficient evidence of a protective effect to warrant continued investigation of the role of soyfoods in cancer prevention, and in vitro, animal, and epidemiological data are examined.
Abstract: International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of can...

1,369 citations


Journal ArticleDOI
TL;DR: The vitreous levels of the angiogenic polypeptide vascular endothelial growth factor were measured and compared in eyes with and without proliferative diabetic retinopathy, and these data are consistent with vascular endothelium growth factor serving as a physiologically relevantAngiogenic factor in proliferative diabetes Retinopathy.

1,185 citations


Journal ArticleDOI
TL;DR: Hours per year of sports participation and levels of sports par ticipation decreased in all groups and factors that correlated with patients who had late surgery for a meniscal tear or an ACL reconstruction were preinjury hours of sports Participation, arthrometer surements, and patient age.
Abstract: We followed 292 patients who had sustained an acute traumatic hemarthrosis for a mean of 64 months. The KT-1000 arthrometer measurements within 90 days of injury revealed the injured knee was stable in 56 pa tients and unstable in 236. Forty-five unstable patients had an ACL reconstruction within 90 days of injury. Sur gical procedures performed >90 days after injury in cluded ligament reconstruction in 46 patients. Factors that correlated with patients who had late surgery for a meniscal tear or an ACL reconstruction (P < 0.05) were preinjury hours of sports participation, arthrometer mea surements, and patient age.Follow-up data are presented for the patients divided into four groups: I, early stable, no reconstruction; II, early unstable, no reconstruction; III, early recon struction; and IV, late reconstruction. No patient changed occupation because of the knee injury. Hours per year of sports participation and levels of sports par ticipation decreased in all groups. Joint arthrosis was documented by ...

1,175 citations


Journal ArticleDOI
TL;DR: The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new insights into the location and function of these tiny protrusions in the CNS.
Abstract: Dendritic spines, the tiny protrusions that stud the surface of many neurons, are the location of over 90% of all excitatory synapses that occur in the CNS. Their small size has, in large part, made them refractory to conventional experimental approaches. Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic onditions. Since the seminal mathematical analyses of D’Arcy Thompson (1992), the power of quantitatively establishing key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines, highly precise determinations of structure and its variation are again proving to be essential for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has, in fact, produced a flurry of

1,005 citations


Journal ArticleDOI
TL;DR: Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung, and have opened a new horizon of therapeutic possibilities for pulmonary medicine.
Abstract: Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The chemical products of NOS in the lung vary with disease states, and are involved in pulmonary neurotransmission, host defense, and airway and vascular smooth muscle relaxation. Further, certain patients with pulmonary hypertension, adult respiratory distress syndrome and asthma may experience physiologic improvement with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous and exogenous NOx react readily with oxygen, superoxide, water, nucl...

915 citations


Journal ArticleDOI
01 Mar 1994-Blood
TL;DR: The frequency of DVT/PE justifies controlled trials of primary prophylaxis in high-risk groups, and therapeutic trials to determine optimal treatment.

885 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the prevalence of asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11-year old children in West Germany and East Germany.
Abstract: The German reunification offers a unique opportunity to study the impact of environmental factors on the development of childhood respiratory and allergic disorders in ethnically similar populations. We investigated the prevalence of asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11-year old children in West Germany (n = 5,030) and East Germany (n = 2,623). A self-administered questionnaire was distributed to the parents. Children underwent cold air challenge and allergy skin prick tests. Atopic sensitization was considerably more frequent in West German children than in their peers in East Germany (36.7% versus 18.2%; odds ratio [OR] = 2.6, p < 0.0001). The prevalence of current asthma and hay fever was significantly higher in West Germany when compared with that in East Germany (5.9% versus 3.9%; OR = 1.5, p < 0.0001 and 8.6% versus 2.7%; OR = 3.4, p < 0.0001, respectively). Bronchitis, however, was more prevalent in East Germany than in the western part of the country. The prevalence of BHR as assessed by cold air challenge was higher in West Germany compared with that in East Germany (8.3% versus 5.5%, OR = 1.6, p < 0.001). Logistic regression showed that the West German study area was no longer a significant independent determinant of asthma once sensitization to mites, cats, and pollen was taken into account. We conclude that sensitization to aeroallergens is strikingly more frequent in West Germany than in East Germany and this may explain the differences in the prevalence of asthma and hay fever between the two parts of the country.

823 citations


Journal ArticleDOI
TL;DR: The responses to soy protein are potentially beneficial with respect to risk factors for breast cancer and may in part explain the low incidence of Breast cancer and its correlation with a high soy intake in Japanese and Chinese women.

Journal ArticleDOI
24 Sep 1994-BMJ
TL;DR: Migraine is a common cause of headache in children and causes significantly reduced school attendance, with male preponderance in children under 12 and femalepreponderance thereafter.
Abstract: Objectives: To determine the prevalence rates of the various causes of severe headache in school-children, with special emphasis on migraine and its impact on school attendance. Design: Population based study in two stages, comprising an initial screening questionnaire followed by clinical interviews and examination of children with symptoms and a control group of asymptomatic children matched for age and sex. Setting: 67 primary and secondary schools in the city of Aberdeen. Subjects: 2165 children, representing a random sample of 10% of schoolchildren in Aberdeen aged 5-15 years. Main outcome measures: (a) the prevalence of20migraine (International Headache Society criteria) and of other types of headache; (b) the impact of migraine on school attendance. Results: The estimated prevalence rates of migraine and tension headache were 10.6% (95% confidence interval 9.1 to 12.3) and 0.9% (0.5 to 1.5) respectively. The estimated prevalence rates for migraine without aura and migraine with aura were 7.8% (95% confidence interval 6.5 to 9.3) and 2.8% (2.0 to 3.8) respectively. In addition, 10 children (0.7%) had headaches which, though lasting less than two hours, also fulfilled the International Headache Society criteria for migraine, 14 (0.9%) had tension headaches, and 20 (1.3%) had non-specific recurrent headache. The prevalence of migraine increased with age, with male preponderance in children under 12 and female preponderance thereafter. Children with migraine lost a mean of 7.8 school days a year due to all illnesses (2.8 days (range 0-80) due to headache) as compared with a mean of 3.7 days lost by controls. Conclusions: Migraine is a common cause of headache in children and causes significantly reduced school attendance.

Journal ArticleDOI
TL;DR: The DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12 that showed a close correlation with age of onset of symptoms and disease severity.
Abstract: Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7–23 in normal individuals. In patients one allele was expanded to between 49–75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.

Journal ArticleDOI
TL;DR: Screening in a school district in central Italy can detect large numbers of cases of coeliac disease, which can be treated with a gluten-free diet and would not be detected by screening only a selected group of at-risk patients.

Journal ArticleDOI
TL;DR: For example, this paper showed that autistic patients and patients with acquired cerebellar lesions were similarly impaired in a task requiring rapid and accurate shifts of attention between auditory and visual stimuli.
Abstract: MRI and autopsy evidence of early maldevelopment of cerebellar vermis and hemispheres in autism raise the question of how cerebellar maldevelopment contributes to the cognitive and social deficits characteristic of autism Compared with normal controls, autistic patients and patients with acquired cerebellar lesions were similarly impaired in a task requiring rapid and accurate shifts of attention between auditory and visual stimuli Neurophysiologic and behavioral evidence rules out motor dysfunction as the cause of this deficit These findings are consistent with the proposal that in autism cerebellar maldevelopment may contribute to an inability to execute rapid attention shifts, which in turn undermines social and cognitive development, and also with the proposal that the human cerebellum is involved in the coordination of rapid attention shifts in a fashion analogous to its role in the coordination of movement

Journal ArticleDOI
TL;DR: A technique is described for correction of distal hypospadias with minimal chordee by tubularizing the urethral plate by deep longitudinal incision of the plate, which allows for tubularization without the need for additional flaps.

Journal ArticleDOI
TL;DR: The results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemang iomas.
Abstract: Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.

Journal ArticleDOI
TL;DR: A triple-risk model for the pathogenesis of SIDS is proposed, which suggests that heterogeneous disorders may make the infant vulnerable to sudden death during the critical period, as potentially exemplified by two previously reported lesions in SIDS brains.
Abstract: Neuropathologic studies in SIDS victims support the concept that they are not entirely ‘normal’ prior to death, but rather possess underlying vulnerabilities which put them at risk for sudden death. T

Journal ArticleDOI
21 Apr 1994-Nature
TL;DR: The structure of a bacterial superantigen bound to a human class II histocompatibility complex molecule (HLA-DR1) has been determined by X-ray crystallography and suggests a model for ternary complex formation with the T-cell antigen receptor (TCR), in which unconventional TCR-MHC contacts are possible.
Abstract: The structure of a bacterial superantigen, Staphylococcus aureus enterotoxin B, bound to a human class II histocompatibility complex molecule (HLA-DR1) has been determined by X-ray crystallography. The superantigen binds as an intact protein outside the conventional peptide antigen-binding site of the class II major histocompatibility complex (MHC) molecule. No large conformational changes occur upon complex formation in either the DR1 or the enterotoxin B molecules. The structure of the complex helps explain how different class II molecules and superantigens associate and suggests a model for ternary complex formation with the T-cell antigen receptor (TCR), in which unconventional TCR-MHC contacts are possible.

Journal ArticleDOI
TL;DR: It is concluded that TTF-1 and HNF-3 are major activators of lung-specific genes and proposed that these factors are involved in a general mechanism of Lung-specific gene transcription.
Abstract: We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73. In this study, we further show that this region is a complex binding site for thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3 (HNF-3). Whereas TTF-1 bound two highly degenerate and closely spaced sites, HNF-3 proteins bound a TGT3 motif (TGTTTGT) that is also found in several liver-specific gene regulatory regions, where it appears to be a weak affinity site for HNF-3. Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity. In addition, we developed a cotransfection assay and showed that a family of lung-specific gene promoters that included the SPB, SPC, SPA, and Clara cell secretory protein (CCSP) gene promoters were specifically activated by cotransfected TTF-1. We conclude that TTF-1 and HNF-3 are major activators of lung-specific genes and propose that these factors are involved in a general mechanism of lung-specific gene transcription. Importantly, these data also show that common factors are involved in organ-specific gene expression along the mammalian foregut axis.

Journal ArticleDOI
TL;DR: Although the mortality rate for these neoplasms exceeds the rates for many other childhood tumors, recent therapeutic advances coupled with refinements in neuroimaging techniques, have increased the percentage of affected children who survive to .
Abstract: Tumors of the central nervous system constitute the largest group of solid neoplasms in children and are second only to leukemia in their overall frequency during childhood. Each year, brain tumors develop in approximately 1500 to 2000 children in the United States; the number of tumors appears to have increased slightly from 1974 to 19881–3. Although the mortality rate for these neoplasms exceeds the rates for many other childhood tumors, recent therapeutic advances coupled with refinements in neuroimaging techniques, which have facilitated earlier diagnosis and improved treatment planning, have increased the percentage of affected children who survive to . . .

Journal ArticleDOI
TL;DR: The results suggest that bFGF in urine deserves further evaluation of its potential use as a monitor of therapy or as a predictor of outcome once a cancer has been diagnosed.
Abstract: BACKGROUND Experimental evidence supports the hypothesis that the development of blood vessels is fundamental to the growth and metastasis of solid tumors. Elevated levels of the angiogenic peptide basic fibroblast growth factor (bFGF) have been significantly correlated with the status and extent of disease in bladder cancer. PURPOSE We measured the bFGF levels in patients with cancer in organs other than the bladder to determine whether elevated levels accompany these cancers. METHODS Urine samples were collected from 950 patients having a wide variety of solid tumors, leukemia, or lymphoma and from a control group of 87 healthy volunteers and 198 patients with non-cancer-related diseases. Levels of bFGF in samples prepared from the urine were measured using an enzyme bioassay. RESULTS Male control subjects had a median bFGF level of 151 pg/g and female control subjects a median of 237 pg/g, with a combined 90th percentile of 619 pg/g. An elevated level of bFGF was found in the urine of some of the patients with every type of tumor studied except cervical carcinoma. For example, patients with active local cancers had a median level of 312 pg/g. Those with active, metastatic cancers had a median level of 479 pg/g and a 90th percentile level of 14143 pg/g. After "elevated" was defined to mean higher than the 90th percentile level for controls, 31% of patients with local active and 47% of patients with metastatic active cancers showed elevated bFGF levels. Survival among cancer patients at the median follow-up time was 85%-88% for those with "normal" and 71%-72% for those with "elevated" urine bFGF levels. IMPLICATIONS Our results suggest that bFGF in urine deserves further evaluation of its potential use as a monitor of therapy or as a predictor of outcome once a cancer has been diagnosed.

Journal ArticleDOI
12 Mar 1994-BMJ
TL;DR: In this article, the authors investigated the relation between skin test reactivity in children and number of siblings and found that decreasing family size may contribute to the increased prevalence of atopic diseases reported in Western countries over the past few decades.
Abstract: Objective: To investigate the relation between skin test reactivity in children and number of siblings. Design: Cross sectional survey among school-children aged 9-11 years. Skin prick tests in the children and self completion of written questionnaire by their parents. Subjects: 5030 children in Munich and 2623 children in Leipzig and Halle, Germany. Main outcome measures: Atopic status assessed by skin prick tests. Results: After possible confounders were controlled for, the prevalence of atopic sensitisation decreased linearly with increasing number of siblings (odds ratio=0.96 for one sibling, 0.67 for five or more siblings; P=0.005). In atopic children the severity of the skin test reaction as assessed by the weal size was not associated with the number of siblings. Conclusions: Factors directly or indirectly related to the number of siblings may decrease the susceptibility of children to become atopic. Thus, declining family size may in part contribute to the increased prevalence of atopic diseases reported in Western countries over the past few decades.

Journal ArticleDOI
TL;DR: Elevated levels of dioxins and PCB can alter the human thyroid hormone status, and higher PCDD, PCDF, and PCB levels in human milk correlated significantly with lower plasma levels of maternal total triiodothyronine and total thyroxine and with higher Plasma levels of TSH in the infants in the 2nd wk and 3rd mo after birth.
Abstract: Dioxins [polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)] and polychlorinated biphenyls (PCB) are potentially hazardous compounds. Animal studies have demonstrated that PCDD, PCDF, and PCB can alter thyroid hormone homeostasis. We investigated thyroid hormone levels in 105 mother-infant pairs. To estimate maternal and infant exposure, four nonplanar PCB congeners were measured in maternal plasma during the last month of pregnancy and in umbilical cord plasma. Seventeen PCDD and PCDF congeners, three planar PCB congeners, and 23 nonplanar PCB congeners were measured in human milk. Higher PCDD, PCDF, and PCB levels in human milk, expressed as toxic equivalents, correlated significantly with lower plasma levels of maternal total triiodothyronine and total thyroxine, and with higher plasma-levels of TSH in the infants in the 2nd wk and 3rd mo after birth. Infants exposed to higher toxic equivalents levels had also lower plasma free thyroxine and total thyroxine levels in the 2nd wk after birth. We conclude that elevated levels of dioxins and PCB can alter the human thyroid hormone status.

Journal ArticleDOI
TL;DR: Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.
Abstract: Background Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. Methods In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. Results Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical exami...

Journal ArticleDOI
TL;DR: The results indicate that high‐frequency oscillatory ventilation, utilizing an aggressive volume recruitment strategy, results in significant improvement in oxygenation compared with a conventional ventilatory strategy designed to limit increases in peak airway pressures.
Abstract: Objective:To compare the effectiveness of high-frequency oscillatory ventilation with conventional mechanical ventilation in pediatric patients with respiratory failure.Setting:Five tertiary care pediatric intensive care units.Design:A prospective, randomized, clinical study with crossover.Patients:

Journal ArticleDOI
TL;DR: In this article, the authors analysed the CAG expansion in different tissues from 12 affected individuals and found that all tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm.
Abstract: Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

Journal ArticleDOI
TL;DR: It is demonstrated that APP processing to potentially amyloidogenic COOH-terminal derivatives occurs in either the endoplasmic reticulum or Golgi complex and can be modulated by the state of cellular energy metabolism.

Journal ArticleDOI
TL;DR: The validity of the 24-hour recall, 3-day food record, and 5day food frequency was assessed to decide on a dietary assessment method for the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study as discussed by the authors.
Abstract: Objective The validity of the 24-hour recall, 3-day food record, and 5-day food frequency was assessed to decide on a dietary assessment method for the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. Design All subjects were assigned to one of three dietary assessment methods. Unobtrusive observers recorded types and amounts of foods eaten during lunch, and these were compared with the foods reported by the girls in the study. Setting School lunchrooms in California and Ohio. Subjects 58 girls, aged 9 and 10 years. Main outcome measures Reporting errors for dietary assessment methods. Statistical analyses performed Descriptive statistics, matched pair t tests, and Spearman correlation coefficients. Results Comparison of the intakes of energy and selected macronutrients showed different ranges of, and median percentage absolute errors for, each dietary assessment method. Percentage absolute errors ranged between 20 and 33 for the 5-day food frequency method; 19 and 39 for the 24-hour recall; and 12 and 22 for the 3-day food record. The proportion of missing foods (ie, observed food items not reported) and phantom foods (ie, reported food items not observed) by each method were 46% and 40%, respectively, for the 5-day food frequency; 30% and 33%, respectively, for the 24-hour recall; and 25% and 10%, respectively, for the 3-day food record. Applications/conclusions Errors in food reporting and quantification can vary with the type of dietary methodology. Agreement between observed and reported intakes from 3-day food records made it the best overall choice. On this basis, it was selected as the method of assessment for the NHLBI Growth and Health Study.

Journal ArticleDOI
TL;DR: It is suggested that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.
Abstract: BACKGROUND Myocardial damage in myocarditis is mediated, in part, by immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki disease, as well as in murine myocarditis. Since 1990, the routine management of presumed acute myocarditis at Children's Hospital, Boston, and Children's Hospital, Los Angeles, has included administration of high-dose IVIG. METHODS AND RESULTS We treated 21 consecutive children presenting with presumed acute myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive therapies. A comparison group comprised 25 recent historical control patients meeting identical eligibility criteria but not receiving IVIG therapy. Left ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3 weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation, the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor fractional shortening. Compared with the non-IVIG group, those treated with IVIG had a smaller mean adjusted left ventricular end-diastolic dimension and higher fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033, respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin-converting enzyme inhibitors, patients treated with IVIG were more likely to achieve normal left ventricular function during the first year after presentation (P = .03). By 1 year after presentation, the probability of survival tended to be higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no adverse effects of IVIG administration. CONCLUSIONS These data suggest that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.