Asthma prevalence disparities and differences in sociodemographic associations with asthma, between Native Hawaiian/Other Pacific Islander, Asian, and White adults in Hawaii - Behavioral Risk Factor Surveillance System (BRFSS), 2001-2010.

OBJECTIVES: Despite high asthma prevalence, relatively little is known about the epidemiology of asthma in Hawaii or among Native Hawaiian/Other Pacific Islanders (NHOPI). We sought to better characterize racial/ethnic differences in asthma prevalence and in sociodemographic factors associated with asthma among Hawaii adults. DESIGN: We conducted multivariable logistic regression using 2001-2010 Behavioral Risk Factor Surveillance System data from Hawaii, and computed adjusted prevalence and ratios. RESULTS: Asthma prevalence markedly varied between self-identified census categories of race in Hawaii, with NHOPI having the highest estimates of both lifetime (20.9%, 95% confidence interval [CI]: 19.5%-22.4%) and current (12.2%, CI: 11.2%-13.3%) asthma. Highest asthma prevalence among NHOPI persisted after controlling for potential confounders and within most sociodemographic categories. Among females Asians reported the lowest asthma prevalence, whereas among males point estimates of asthma prevalence were often lowest for Whites. Females often had greater asthma prevalence than males of the same race, but the degree to which gender modified asthma prevalence differed by both race and sociodemographic strata. Gender disparities in asthma prevalence were greatest and most frequent among Whites, and for current asthma among all races. Sociodemographic factors potentially predictive of adult asthma prevalence in Hawaii varied by race and gender. CONCLUSION: Asthma disproportionately affects or is recognized more often among women and NHOPI adults in Hawaii, and occurs less or is under-reported among Asian women. The sociodemographic characteristics included in this study's model did not explain asthma disparities between races and/or gender. This investigation provides a baseline with which to plan additionally needed prevention programs, epidemiological investigations, and surveillance for asthma in Hawaii.

Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies.

Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.

Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice.

Iodine-125-labeled monoclonal antibody 108.4 (108.4 mAb), raised against the extracellular domain of the epidermal growth factor (EGF) receptor, was shown to visualize sc xenografts of human oral epidermoid carcinoma (KB) cells in nude mice. In vitro, although EGF caused an increase in the number of KB cell colonies (150% at a concentration of 160 mM), the anti-EGF receptor antibodies reduced clone formation. At a concentration at which EGF caused a 50% increase in colony number, the addition of a 100-fold molar excess of 108.4 mAb resulted in a decrease in the number of cell colonies to 20% of the original value. Therefore, the effect of antibody on the KB tumor was studied in vivo in three different modes of tumor transplantation. Antitumor activity was demonstrated first by retardation (versus controls) of the growth of tumor cells as sc xenografts (P greater than .017), then by prolongation of the life span of animals with the ip form of the tumor (P less than .001), and finally on an experimental lung metastasis by a reduction in the number and size of tumors (P less than .05). When the anti-EGF receptor antibodies were added together with cisplatin, the antitumor effect was greatly enhanced, suggesting that the toxic activity of these agents is synergistic (P less than .007). The antitumor effect persisted when animals were treated with the F(ab)'2 fragment of the antibody, although it was less efficient. The Fab fragment of the antibody, whose ability to bind to the cell-associated receptor was completely conserved, did not affect the growth of the tumor. The activity manifested by the F(ab)'2 fragment of the anti-EGF receptor antibodies suggested that the antitumor effect was not due to immune mechanisms requiring the Fc portion of the antibody.

The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities.

Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity.

The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies.

Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies.

Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells.

The HER-2/neu protooncogene (also called erbB-2) encodes a tyrosine kinase receptor for a polypeptide growth-regulatory molecule. Amplification and overexpression of the gene have been frequently observed in human adenocarcinomas and correlated with poor prognosis. To explore the potential of antibody therapy directed at the HER-2/Neu receptor, we have raised a panel of murine monoclonal antibodies to the human protein, and tested their effect on the tumorigenic growth of HER-2/neu-transfected fibroblasts in athymic mice. We previously reported that the i.p. injected antibodies either inhibited or accelerated the tumorigenic growth of HER-2/neu transfectants in athymic mice. Here we report that these opposing effects were induced also by i.v. injected antibodies, they lasted over 7 weeks, and were probably mediated by distinct epitopes on the receptor molecule. To understand the cellular mechanisms underlying antibody-induced tumor inhibition, we tested the effect of the monoclonal antibodies on various cultured human breast cancer cells. Our analysis revealed that the tumor-inhibitory antibodies specifically induced phenotypic cellular differentiation that included growth arrest at late S or early G2 phase of the cell cycle, markedly altered cytoplasm and nuclear morphology, synthesis and secretion of milk components (casein and lipids), and translocation of the HER-2/Neu protein to cytoplasmic and perinuclear sites. The extent of cellular differentiation by various antibodies could be correlated with their tumor-inhibitory potential, whereas a tumor-stimulatory monoclonal antibody or control immunoglobulin were completely inactive with respect to cellular differentiation. Taken together, our in vivo and in vitro studies correlate the tumor inhibitory potential of monoclonal antibodies to HER-2/Neu with their capacity to induce cellular differentiation in vitro. This observation may hold promise for immunotherapy of cancers that express the HER-2/neu oncogene.

A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors.

ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is frequently associated with an aggressive clinical course of certain human adenocarcinomas, the encoded protein is an attractive target for immunotherapy. Indeed, certain monoclonal antibodies (mAbs) to ErbB-2 effectively inhibit tumor growth in animal models and in clinical trials, but the underlying mechanism is incompletely understood. To study this question, we generated a large battery of mAbs to ErbB-2, that were classified epitopically. Whereas most antibodies stimulated tyrosine phosphorylation of ErbB-2, their anti-tumor effect correlated with its accelerated endocytic degradation. One group of tumor-inhibitory mAbs (Class II mAbs) was elicited by the most antigenic site of ErbB-2, and inhibited in trans binding of NDF and EGF to their direct receptors. The inhibitory effect was due to acceleration of ligand dissociation, and it resulted in the reduction of the ability of ErbB-2 to transactivate the mitogenic signals of NDF and EGF. These results identify two potential mechanisms of antibody-induced therapy: acceleration of ErbB-2 endocytosis by homodimerization and blocking of heterodimerization between ErbB-2 and growth factor receptors.

Spectrum of neurological deficits in experimental CNS ischemia. A quantitative study.

The sequence of events in focal cerebral ischemia has been difficult to study quantitatively in humans. Experimental investigation of these phenomena has been impeded because reproducible animals models that simulate human stroke are lacking. We have developed a rabbit spinal cord ischemia model that resembles human stroke patterns in many respects. Using this model, we have found that (1) brief ischemia produces completely reversible neurological deficits; (2) intermediate ischemic periods may produce transiently reversible deficits that later progress without further manipulation; (3) prolonged ischemia produces irreversible lesions in all animals. The model should be useful for studies of the pathophysiological mechanisms of CNS ischemia.

Guillain-Barré syndrome in the United States, 1978-1981: additional observations from the national surveillance system.

During the period January 1978-March 1981, 2,575 cases of Guillain-Barré syndrome (GBS) were reported by participating neurologists in the national GBS surveillance system. The incidence of GBS was highest in the 50- to 74-year-old age group, but a lesser peak was observed in persons aged 15 to 35. The frequencies of antecedent respiratory (43%) and gastrointestinal (21%) illness exceeded frequencies of such illnesses in the US population (10 and 0.8%, respectively), based on survey data compiled by the National Center for Health Statistics; the differences in these frequencies of illness were similar in all seasons of the year, in males and in females, and in persons less than 6, 6 to 16, 17 to 44, and greater than 44 years of age. Nineteen percent of adult patients for whom information was available (67% of the total) reported receiving an A/New Jersey influenza vaccine in 1976, a lower percentage than would be expected on the basis of a survey conducted in that year. The data suggest that persons who received this vaccine have not been at increased risk and may even have been at decreased risk of acquiring GBS during the period covered by this study.

Results of the national surveillance for Guillain-Barré syndrome.

The preliminary results of the national surveillance for Guillain-Barré syndrome(GBS) are reported. In the first 6 months of 1978, 327 cases of GBS were reported to the Center for Disease Control (CDC). A statistically significant difference was observed between sex-specific attack rates, and a direct correlation also was observed between advancing age and increasing risk of GBS.

National surveillance for Guillain-Barré syndrome: January 1978-March 1979.

Between January 1, 1978, and March 31, 1979, 1,034 cases of Guillain-Barré syndrome (GBS) were reported to the Centers for Disease Control by the 1,813 American Academy of Neurology sentinel physicians who participated in the national GBS surveillance program. A direct correlation was observed between increasing age and the age-specific attack (incidence) rates. Based on the cases observed and the total US population, age-adjusted attack rates were statistically higher in males (0.52 per 100,000) than in females (0.40). Rates for whites were 0.44 and those for blacks 0.28 per 100,000; although the difference is statistically significant, uncertainties as to the true denominators by race preclude acceptance of these differences as valid. Sixty-seven percent, or 682 of the patients, reported that they had had an antecedent illness within 8 weeks before onset of GBS, and among them the peak period of onset of GBS was in the second week after the onset of the prior illness. There were also 52 patients (5%) who had undergone surgery and 45 (4.5%) who had received vaccinations, both within the 8 weeks before onset of GBS. However, the high proportions of antecedent illness in these groups (45% of those operated and 53% of those vaccinated) made attribution of GBS to the procedures tenuous. Risk of GBS in patients who reported receiving a swine influenza vaccination in 1976 was no greater than in those who reported that they did not receive this vaccine.

Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.

The covalent linking of two nucleotide analogues to antibodies.

Two anticancer drugs, antagonists of nucleic acids, were covalently linked to antibodies specifically reactive with B leukemia cells and thus with a potential possibility of drug targeting to the tumor site. The drugs cytosine 1-beta-D-arabinoside and 5-fluorouridine, competitive inhibitors of enzymes involved in DNA synthesis, were linked to antibodies via a dextran bridge. Cytosine 1-beta-D-arabinoside was linked to periodate-oxidized dextran and fluorouridine to dextran hydrazide. The dextran derivatives were in turn linked to antibodies that recognized a specific membrane IgM on B leukemia cells. The drug-antibody conjugates maintained most of the original antigen-binding capacity of the antibody and the full pharmacological activity of the drugs.

A cluster of cases of Reye syndrome associated with chickenpox.

In the spring of 1980, four confirmed, and three possible cases of Reye syndrome, each associated with a chickenpox prodromal illness, were identified in Las Cruces, NM. One patient, a 5-year-old girl, died. Cases tended to occur in one section of the community, among children attending two of the 16 elementary schools. A telephone survey of parents with school-aged children (6 to 9 years old) suggested that a significantly greater attack rate of chickenpox occurred in children attending those two schools. Based upon this survey and the expected distribution of chickenpox among children less than 15 years of age, the incidence of Reye syndrome following chickenpox infection in the county in which Las Cruces is located was estimated to be 2.5/10,000 cases of chickenpox; these data reveal a four- to ninefold greater incidence of Reye syndrome than that following influenza B infections, which was previously estimated based upon a cluster of five cases in a county in Michigan. Additional investigations of Reye syndrome clusters are needed in an effort to identify and study suspected risk factors and to better define the relationship between Reye syndrome and viral infections.

National surveillance of Kawasaki disease.

Information about 261 cases of Kawasaki disease (KD) was reported to the Center for Disease Control (CDC) between July 1976 and July 1978. KD occurred at all times of the year in young, previously healthy children throughout the United States. KD was more common in infants and toddlers, males, and Asian and part-Asian children. The illness was characterized by acute onset of prolonged high fever; maculopapular or scarlatiniform rash; adenopathy; injection of the conjunctival and mucous membranes of the upper respiratory tract; redness of the palms and soles; indurative edema of the extremities; desquamation, arthralgias; and elevated white blood cell count, erythrocyte sedimentation rate, and platelet count. Complications included gallbladder disease and carditis; 2.8% died. Surviving patients were hospitalized for a mean of 8.9 days.

National surveillance for Reye syndrome: a five-year review.

National surveillance for Reye syndrome conducted during five years, including the period 1973-1974 and December 1976 through November 1980, has resulted in the reporting of more than 2,000 cases of Reye syndrome. The highest reported incidence of Reye syndrome occurred during years of primary influenza B and A (H1N1) activity; the reported incidence during one period of influenza A (H3N2) activity was somewhat lower. Regional outbreaks of Reye syndrome have been associated with influenza A (H1N1) and B but now with influenza A (H3N2). Cases of Reye syndrome in whites tend to be distributed throughout all age groups whereas a large percentage of cases in blacks have been reported in infants less than 1 year of age in three of the past four years. Nationally, there has been a decline in the case-fatality ratio in recent years.

Risk of respiratory illness associated with day-care attendance: a nationwide study.

The risk of respiratory and other illnesses in children (age groups: 6 weeks through 17 months, 18 through 35 months, and 36 through 59 months) in various types of day-care facilities was studied. Children considered exposed to day care were those who were enrolled in day care with at least one unrelated child for at least 10 hours per week in each of the 4 weeks before the interview; unexposed children were not enrolled in any regular child care with unrelated children and did not have siblings younger than 5 years of age receiving regular care with unrelated children. Although an increased risk of respiratory illness was associated with attending day care for children in all three age groups, this risk was statistically significant only for children 6 weeks through 17 months of age (odds ratio = 1.6; 95% confidence interval = 1.1 to 2.4) and children 18 through 35 months of age who had no older siblings (odds ratio = 3.4; 95% confidence interval = 2.0 to 6.0). In contrast, day-care attendance was not associated with an increased risk of respiratory illness in children 18 through 35 months of age with older siblings (odds ratio = 1.0). For children aged 6 weeks through 17 months, the exposure to older siblings was associated with an increased risk of respiratory illness; however, for children aged 36 through 59 months, older siblings were protective against respiratory illness. In addition, for the children in each age group currently in day care, increased duration of past exposure to day care was associated with a decreased risk of respiratory illness.(ABSTRACT TRUNCATED AT 250 WORDS)

National Reye syndrome surveillance, 1982.

Despite the fact that influenza B was the primary influenza virus strain during the winter of 1981-1982, only 213 cases of Reye syndrome were reported to the Centers for Disease Control (CDC) between Dec 1, 1981 and Nov 30, 1982. This national reported incidence of 0.33 cases per 100,000 children less than 18 years of age is the lowest reported incidence since the Centers for Disease Control began surveillance in 1973. This relatively low incidence probably reflected, at least in part, the fact the influenza B activity was spotty and the illness relatively mild the winter of 1981-1982. The 213 cases were reported from 43 states; and in 56% of the patients, Reye syndrome occurred following a respiratory illness. The mean age of the children was 7.0 years; there were equal numbers of girls and boys; and 93% were white. Of the ten black patients, 80% were less than 1 year of age compared with 9% of the white patients. Of the 208 patients with reported admission stage, 45% were admitted in stage I or 0, a slightly lower proportion than that observed in the previous 2 years. Salicylate levels were obtained in 55% of the patients and were reported as "detectable" in 81% compared with 96% in 1981 (P = .003, chi 2). Of the 200 patients with known outcome, 70 patients died (a case fatality ratio of 35%).

Changing epidemiology of Reye syndrome in the United States.

The average annual incidence of Reye syndrome reported through national surveillance was lower during 1981 to 1984 than during the previous five surveillance years. This is accounted for by a decrease in cases among children younger than 10 years of age; the number of cases in 10- to 19-year-old persons remained relatively stable during this period. The overall decline in incidence and the differing age-specific incidence trends are apparent for both varicella-associated cases and for nonvaricella-associated cases. During 1985, the incidence has been much lower than during any previous year since surveillance was initiated; this most recent decrease includes children 10 to 19 years of age. Independently conducted surveys suggest that the prevalence of salicylate use for viral illnesses has decreased among children in recent years, particularly among children younger than 10 years of age. The changing epidemiology of Reye syndrome may reflect, in part, the declining use of salicylates among children and teenagers in the United States.

Outbreak of Kawasaki syndrome in Denver, Colorado: association with rug and carpet cleaning.

Between October 1984 and January 1985, the largest outbreak of Kawasaki syndrome reported to date in the continental United States (62 cases) occurred in the Front Range of the Rocky Mountains, extending from Colorado Springs, Colorado, to Cheyenne, Wyoming. Fifty-two (84%) of these Kawasaki syndrome patients lived in the Denver metropolitan area. A case-control study revealed that 16 (62%) of 26 Kawasaki syndrome patients compared with 10 (20%) of 49 matched control subjects had a history of exposure to shampooed (19%) or spot-cleaned (81%) rugs or carpets within 30 days of the Kawasaki syndrome onset date (odds ratio = 5, P less than .01). The time of exposure to shampooed or spot-cleaned rugs or carpets for 9 of 10 Kawasaki syndrome patients who had a single exposure and for all 6 Kawasaki syndrome patients who had multiple exposures were clustered within an interval 13 to 30 days before the onset of illness. Although the reason for this unusually large outbreak remains obscure, it is the third in which a statistically significant association between Kawasaki syndrome and rug or carpet cleaning has been found.