Showing papers by "Johns Hopkins University published in 1992"
TL;DR: Three participants are identified (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.
3,098 citations
TL;DR: The paper presents an SA algorithm that is based on a simultaneous perturbation gradient approximation instead of the standard finite-difference approximation of Keifer-Wolfowitz type procedures that can be significantly more efficient than the standard algorithms in large-dimensional problems.
Abstract: The problem of finding a root of the multivariate gradient equation that arises in function minimization is considered. When only noisy measurements of the function are available, a stochastic approximation (SA) algorithm for the general Kiefer-Wolfowitz type is appropriate for estimating the root. The paper presents an SA algorithm that is based on a simultaneous perturbation gradient approximation instead of the standard finite-difference approximation of Keifer-Wolfowitz type procedures. Theory and numerical experience indicate that the algorithm can be significantly more efficient than the standard algorithms in large-dimensional problems. >
2,149 citations
TL;DR: Results are consistent with the hypothesis thatMDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control, and this mechanism of tumorigenesis parallels that for virally-induced tumours.
Abstract: Despite extensive data linking mutations in the p53 gene to human tumorigenesis, little is known about the cellular regulators and mediators of p53 function. MDM2 is a strong candidate for one such cellular protein; the MDM2 gene was originally identified by virtue of its amplification in a spontaneously transformed derivative of mouse BALB/c cells and the MDM2 protein subsequently shown to bind to p53 in rat cells transfected with p53 genes. To determine whether MDM2 plays a role in human cancer, we have cloned the human MDM2 gene. Here we show that recombinant-derived human MDM2 protein binds human p53 in vitro, and we use MDM2 clones to localize the human MDM2 gene to chromosome 12q13-14. Because this chromosomal position appears to be altered in many sarcomas, we looked for changes in human MDM2 in such cancers. The gene was amplified in over a third of 47 sarcomas, including common bone and soft tissue forms. These results are consistent with the hypothesis that MDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control. This mechanism of tumorigenesis parallels that for virally-induced tumours, in which viral oncogene products bind to and functionally inactivate p53.
2,006 citations
TL;DR: Evidence is provided that mutations of the APC gene play a major role in the early development of colorectal neoplasms, and the frequency of such mutations remained constant as tumours progressed from benign to malignant stages.
Abstract: HUMAN tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumour suppressor genes1–3 But in no common adult cancer have the mutations that are critical in the early stages of the tumorigenic process been defined We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene Furthermore, the APC gene met two criteria of importance for tumour initiation First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 05 cm in diameter Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal neoplasms
1,957 citations
1,883 citations
1,830 citations
TL;DR: The magnitude and distribution of the public health problem posed by migraine in the United States is described by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence.
Abstract: Objective. —To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence. Design. —In 1989, a self-administered questionnaire was sent to a sample of 15000 households. A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches. Setting. —A sample of households selected from a panel to be representative of the US population in terms of age, gender, household size, and geographic area. Participants. —After a single mailing, 20468 subjects (63.4% response rate) between 12 and 80 years of age responded to the survey. Respondents and non-respondents did not differ by gender, household income, region of the country, or urban vs rural status. Whites and the elderly were more likely to respond. Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria. Results. —17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. The prevalence of migraine varied considerably by age and was highest in both men and women between the ages of 35 to 45 years. Migraine prevalence was strongly associated with household income; prevalence in the lowest income group ( Conclusions. —A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition. (JAMA. 1992;267:64-69)
1,576 citations
TL;DR: In this paper, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described and linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly linked to the Min locus.
Abstract: Germ-line mutations of the APC gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described. Linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly linked to the Min locus. Sequence comparison of mApc between normal and Min-affected mice identified a nonsense mutation, which cosegregated with the Min phenotype. This mutation is analogous to those found in FAP kindreds and in sporadic colorectal cancers.
1,562 citations
TL;DR: Sulforaphane is the most potent inducer, and the presence of oxygen on sulfur enhances potency, which may be a significant component of the anticarcinogenic action of broccoli.
Abstract: Consumption of vegetables, especially crucifers, reduces the risk of developing cancer. Although the mechanisms of this protection are unclear, feeding of vegetables induces enzymes of xenobiotic metabolism and thereby accelerates the metabolic disposal of xenobiotics. Induction of phase II detoxication enzymes, such as quinone reductase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] and glutathione S-transferases (EC 2.5.1.18) in rodent tissues affords protection against carcinogens and other toxic electrophiles. To determine whether enzyme induction is responsible for the protective properties of vegetables in humans requires isolation of enzyme inducers from these sources. By monitoring quinone reductase induction in cultured murine hepatoma cells as the biological assay, we have isolated and identified (-)-1-isothiocyanato-(4R)-(methylsulfinyl)butane [CH3-SO-(CH2)4-NCS, sulforaphane] as a major and very potent phase II enzyme inducer in SAGA broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, like other anticarcinogenic isothiocyanates, and induces phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). To elucidate the structural features responsible for the high inducer potency of sulforaphane, we synthesized racemic sulforaphane and analogues differing in the oxidation state of sulfur and the number of methylene groups: CH3-SOm-(CH2)n-NCS, where m = 0, 1, or 2 and n = 3, 4, or 5, and measured their inducer potencies in murine hepatoma cells. Sulforaphane is the most potent inducer, and the presence of oxygen on sulfur enhances potency. Sulforaphane and its sulfide and sulfone analogues induced both quinone reductase and glutathione transferase activities in several mouse tissues. The induction of detoxication enzymes by sulforaphane may be a significant component of the anticarcinogenic action of broccoli.
1,521 citations
TL;DR: A concurrent operants paradigm was used to compare the Pace et al. (1985) procedure with a modified procedure wherein clients were presented with two stimuli simultaneously and were given access only to the first stimulus approached, resulting in greater differentiation among stimuli.
Abstract: The development of effective training programs for persons with profound mental retardation remains one of the greatest challenges for behavior analysts working in the field of developmental disabilities. One significant advancement for this population has been the reinforcer assessment procedure developed by Pace, Ivancic, Edwards, Iwata, and Page (1985), which involves repeatedly presenting a variety of stimuli to the client and then measuring approach behaviors to differentiate preferred from nonpreferred stimuli. One potential limitation of this procedure is that some clients consistently approach most or all of the stimuli on each presentation, making it difficult to differentiate among these stimuli. In this study, we used a concurrent operants paradigm to compare the Pace et al. (1985) procedure with a modified procedure wherein clients were presented with two stimuli simultaneously and were given access only to the first stimulus approached. The results revealed that this forced-choice stimulus preference assessment resulted in greater differentiation among stimuli and better predicted which stimuli would result in higher levels of responding when presented contingently in a concurrent operants paradigm.
1,507 citations
TL;DR: The observed isotropic giant magnetoresistance (GMR) in nonmultilayer magnetic systems using granular magnetic solids is shown to occur in magnetically inhomogeneous media containing nonaligned ferromagnetic entities on a microscopic scale.
Abstract: We have observed isotropic giant magnetoresistance (GMR) in nonmultilayer magnetic systems using granular magnetic solids. We show that GMR occurs in magnetically inhomogeneous media containing nonaligned ferromagnetic entities on a microscopic scale. The GMR is determined by the orientations of the magnetization axes, the density, and the size of the ferromagnetic entities.
TL;DR: ALS is associated with a defect in high-affinity glutamate transport that has disease, region, and chemical specificity and could lead to neurotoxic levels of extracellular glutamate and thus be pathogenic in ALS.
Abstract: Background. Amyotrophic lateral sclerosis (ALS) is a chronic degenerative neurologic disorder characterized by the death of motor neurons in the cerebral cortex and spinal cord. Recent studies have suggested that the metabolism of glutamate, a potentially neurotoxic amino acid, is abnormal in patients with ALS. We hypothesized that the high-affinity glutamate transporter is the site of the defect. Methods. We measured high-affinity, sodium-dependent glutamate transport in synaptosomes from neural tissue obtained from 13 patients with ALS, 17 patients with no neurologic disease, and 27 patients with other neurodegenerative diseases (Alzheimer's disease in 15 patients and Huntington's disease in 12 patients). The groups were comparable with respect to age and the interval between death and autopsy. Synaptosomes were prepared from spinal cord, motor cortex, sensory cortex, visual cortex, striatum, and hippocampus. We also measured sodium-dependent transport of γ-aminobutyric acid and phenylalanine i...
TL;DR: Observations suggest the feasibility of in vivo CFTR gene transfer as therapy for the pulmonary manifestations of CF.
TL;DR: The most significant factor affecting serum PSA levels with age is the development of prostate disease, and rate of change in PSALevels may be a sensitive and specific early clinical marker for theDevelopment of prostate cancer.
Abstract: Objective. ——To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease. Design. —Case-control study of men with and without prostate disease who were participants in a prospective aging study. Setting. —Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging. Patients. —Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer. Outcome Measures. —Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease. Results. —Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer>BPH>control; P Conclusions. —The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer. ( JAMA . 1992;267:2215-2220)
Book•
01 Jan 1992TL;DR: A-Morphous morphology as mentioned in this paper treats morphology as a rule-governed relations, minimizing the non-phonological internal structure assigned to words and eliminating morphologically motivated boundary elements, and maintains significant distinctions between inflection, derivation, and compounding, in terms of their place in a grammar.
Abstract: In A-Morphous Morphology, Stephen Anderson presents a theory of word structure which relates to a full generative grammar of language. He holds word structure to be the result of interacting principles from a number of grammatical areas, and thus not localized in a single morphological component. Dispensing with classical morphemes, the theory instead treats morphology as a matter of rule-governed relations, minimizing the non-phonological internal structure assigned to words and eliminating morphologically motivated boundary elements. Professor Anderson makes the further claim that the properties of individual lexical items are not visible to, or manipulated by, the rules of the syntax, and assimilates to morphology special clitic phenomena. A-Morphous Morphology maintains significant distinctions between inflection, derivation, and compounding, in terms of their place ina grammar. It also contains discussion of the implications of this new A-Morphous position analysis of word structure.
TL;DR: The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis and document the existence of tumor-specific cell surface molecules resulting from somatic mutation.
Abstract: The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas, and the amplified genes are frequently rearranged. We have characterized the genetic alterations associated with these rearrangements in five malignant gliomas. In one tumor the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR sequence. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erbB oncogenes. Four other tumors were noted to have internal deletions of the EGFR gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Further, these studies document the existence of tumor-specific cell surface molecules resulting from somatic mutation.
TL;DR: In the literature, there are some contradictions with respect to the stimulus modalities to which hyperalgesia and sensitization occur and this contradiction should spawn further investigations into the mechanical response properties of nociceptors and into the molecular mechanisms of heat sensitization.
TL;DR: There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication and contrary to popular opinion, publication bias originates primarily with investigators, not journal editors.
Abstract: Objective. —To investigate factors associated with the publication of research findings, in particular, the association between "significant" results and publication. Design. —Follow-up study. Setting. —Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions—one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health. Population. —A total of 737 studies were followed up. Results. —Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication. Conclusion. —There is a statistically significant association between significant results and publication. (JAMA. 1992;267:374-378)
Journal Article•
TL;DR: It is proposed that local release of IL-4 in vivo in allergic diseases or after experimental allergen challenge may partly explain the enrichment of eosinophils and basophils (vs neutrophils) observed in these situations.
Abstract: The present studies were performed to explore potentially selective mechanisms of leukocyte adhesion in an attempt to understand how preferential recruitment of eosinophils and basophils might occur during allergic and other inflammatory reactions. Stimulation of human vascular endothelial cells for 24 h with IL-4 (30 to 1,000 U/ml) induced adhesion for eosinophils (up to approximately four-fold of control) and basophils (up to approximately twofold of control) but not neutrophils (less than 125% of control). Analysis of endothelial expression of adhesion molecules by flow cytometry revealed that IL-4 treatment induced vascular cell adhesion molecule-1 (VCAM-1) expression without significantly affecting the expression of other adhesion molecules, namely endothelial-leukocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1). The concentration-response curve for IL-4-induced VCAM-1 expression paralleled that for adhesion. Endothelial cells stimulated with IL-4 expressed adhesive properties for eosinophils by 3 h; the response increased steadily during a 24-h time course study. Eosinophils and basophils adhered to plates coated with a recombinant form of VCAM-1. This adhesion was blocked with antibodies to VCAM-1 but not ELAM-1. mAb directed against either VCAM-1 or VLA-4 inhibited (by approximately 75%) the binding of eosinophils and basophils to IL-4-stimulated endothelial cells. Because VLA-4 and VCAM-1 have been demonstrated to bind to each other in other adhesion systems, these results suggest that IL-4 stimulates eosinophil and basophil adhesion by inducing endothelial cell expression of VCAM-1 which binds to eosinophil and basophil VLA-4. The lack of expression of VLA-4 on neutrophils and the failure of IL-4 to stimulate neutrophil adherence support this conclusion. It is proposed that local release of IL-4 in vivo in allergic diseases or after experimental allergen challenge may partly explain the enrichment of eosinophils and basophils (vs neutrophils) observed in these situations.
TL;DR: In this article, the directional hemispherical spectral reflectance of a wide range of natural earth surface materials has been measured and is summarized and used to predict directional spectral emissivity from these data.
TL;DR: A novel base mutation in the same exon of the APP gene which co–segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy is reported, suggesting that the clinically distinct entities can be caused by the same mutation.
Abstract: Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, presenile dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.
TL;DR: In eight of the nine cases, the ras mutations were detectable in DNA purified from the stool, indicating that colorectal tumors can be detected by a noninvasive method based on the molecular pathogenesis of the disease.
Abstract: Colorectal (CR) tumors are usually curable if detected before metastasis. Because genetic alterations are associated with the development of these tumors, mutant genes may be found in the stool of individuals with CR neoplasms. The stools of nine patients whose tumors contained mutations of K-ras were analyzed. In eight of the nine cases, the ras mutations were detectable in DNA purified from the stool. These patients included those with benign and malignant neoplasms from proximal and distal colonic epithelium. Thus, colorectal tumors can be detected by a noninvasive method based on the molecular pathogenesis of the disease.
TL;DR: Evidence is provided that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer.
Abstract: Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk of prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by autosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers revealed that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to be affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.
TL;DR: A significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers, and the multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.
Abstract: In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.
TL;DR: In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume, using an algorithm that relates the regional fraction of GM to partial volume effects.
Abstract: Accuracy in in vivo quantitation of brain function with positron emission tomography (PET) has often been limited by partial volume effects. This limitation becomes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with different degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume. GM PET was applied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetected in the PET image before correction for partial volume effects. In computer simulations, errors in the segmentation of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate determination of the actual radiotracer concentration in human brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM.
TL;DR: Analysis of a 40-bp repeat in the 3' untranslated region of the message revealed variable numbers of the repeat ranging from 3 to 11 copies, which will aid in the investigation of a role for this gene in genetic disorders of the dopaminergic system in humans.
TL;DR: These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.
Abstract: BACKGROUNDThis study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures.METHODS AND RESULTSVentricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV)...
TL;DR: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV and the trend toward decreasing risk with increasingly stringent screening of donors was statistically significant.
Abstract: Background. The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. Methods. From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. Results. Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 p...
TL;DR: In this paper, a class of models for the marginal expectations of each response and for pairwise associations are compared with log-linear models, and the robustness and efficiency of each model is discussed.
Abstract: SUMMARY It is common to observe a vector of discrete and/or continuous responses in scientific problems where the objective is to characterize the dependence of each response on explanatory variables and to account for the association between the outcomes. The response vector can comprise repeated observations on one variable, as in longitudinal studies or genetic studies of families, or can include observations for different variables. This paper discusses a class of models for the marginal expectations of each response and for pairwise associations. The marginal models are contrasted with log-linear models. Two generalized estimating equation approaches are compared for parameter estimation. The first focuses on the regression parameters; the second simultaneously estimates the regression and association parameters. The robustness and efficiency of each is discussed. The methods are illustrated with analyses of two data sets from public health research.