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Biomedical subjects

J E Miller

Publications and source records attributed to J E Miller.

At least 55 records · Page 3Linked to original sources

The effects of race/ethnicity and income on early childhood asthma prevalence and health care use.

OBJECTIVES: Asthma is the most common chronic illness among US children and is most prevalent in low-income and minority groups. We used multivariate models to disentangle the effects of race/ethnicity, income, and other individual-level risk factors on asthma in a population-based sample of children aged 3 years. METHODS: Data are from the 1988 National Maternal and Infant Health Survey and 1991 Longitudinal Follow-Up. Odds ratios of asthma prevalence, hospitalization, and emergency room use were estimated, with control for socioeconomic characteristics, health behaviors, and insurance. RESULTS: Asthma prevalence, hospitalization, and emergency room use declined with increasing income for non-Black but not Black children. CONCLUSIONS: Lifetime income and sociodemographic characteristics do not explain the excess risks of asthma and emergency health care use for asthma among young Black children.

Asthma↗

Efficacy of moxidectin 0.5% pour-on against swine nematodes.

Forty pigs with induced infections of Ascaris suum, Trichuris suis, Metastrongylus spp., Oesophagostomum dentatum and O. quadrispinulatum were assigned to five-dose groups of moxidectin 0.5% pour-on with eight pigs per dose group. The doses were: moxidectin, 0 (vehicle control), 0.75, 1.00, 1.25, and 1.50 mg/kg(-1) body weight. Worm egg counts (EPG) were made from fecal samples collected on Day 2 pretreatment and on Day 14 or 15 post-treatment. Animals were ranked according to the descending order of A. suum egg counts made on Day 2 and blocked in groups of five. Pigs in blocked groups were assigned randomly to each of the five dose groups. Treatment doses were calculated on the basis of weights taken on Day 1 and were administered topically from the neck to the base of the tail. Pigs were housed by pairs in individual pens provided with self-feeders and automatic waterers. Necropsies were performed on equal numbers of pigs from each treatment group on days 14 and 15 post-treatment. Adult and larval worms were collected, identified and counted by standard parasitological techniques. All counts were transformed by Y=log10 (count+1) transformation prior to analysis. A two-way analysis of variance was conducted and treatment effect was tested for significance at the 5% level. Efficacies based on geometric means and optimal doses were as follows: Ascaris suum, 98.3% at 1.25; Metastrongylus spp., 100% at 0.75; Oesophagostomum quadrispinulatum, 100% at 1.50; and Trichuris suis, 93.5% at 0.75. Efficacy for O. dentatum was from 81.3% to 100%; however, the average number of O. dentatum (30) was too small for significance. Two species of lungworms were present, Metastrongylus apri and M. pudendotectus but they were not speciated at necropsy. As reported for several anthelmintics, the efficacy of moxidectin was variable for Trichuris. The highest efficacy was in the 0.75 dose group with six pigs harboring a few or no worms. The lowest efficacy was in the 1.25 group with only two pigs harboring a few or no worms.

Animals↗

An automated semiquantitative B and T cell clonality assay.

BACKGROUND: Rearrangements of the antigen receptor genes in B and T cells generate products of unique length and sequence. Polymerase chain reaction (PCR) assays are routinely used to identify clonal lymphocyte populations by detecting clonal V-J rearrangements or chromosomal translocations within these antigen receptor loci. Multiple primer sets are, however, required to detect the majority of clonal B- and T-cell malignancies. Products from the individual reactions must be analyzed separately to avoid misinterpretation. Moreover, small clonal populations remain difficult to identify. To address these difficulties, we propose that an integrated fluorescence-based approach to clonal B- and T-cell detection would simultaneously identify both B- and T-cell neoplasia; increase amplicon resolution, analytic sensitivity, and assay throughput; produce more comprehensive and semiquantitative data useful for evaluation of hematologic malignancies; and eliminate labor intensive agarose and polyacrylamide gel electrophoresis. METHODS AND RESULTS: Samples were genomic DNA and cDNA. Differentially labeled primers were used to amplify regions diagnostic for B- and T-cell clonality in a single plate with a single thermocycler program. Combined amplicon products underwent capillary electrophoresis for high resolution fractionation and differential fluorescence detection and quantification. Data were automatically analyzed and archived. In a comparative analysis of a variety of clinical samples, this automated and integrated B- and T-cell assay showed >94% agreement (33 of 35 results) with individual B- and T-cell PCR assays. Furthermore, this assay had an overall monoclonality detection rate of 100%, and as little as 100 ng of sample DNA yielded complete B- and T-cell clonality test results. The limit of detection was approximately 10-2 cells, and amplicons were sized to within 0.1 basepair. Serial dilutions of clonal B- and T-cell lines comprising a coded proficiency panel were identified and correctly ranked. Specificity was 100% as determined by analysis of 18 control samples that were all negative for B- and T-cell clonality. CONCLUSIONS: Our data show that this automated and integrated B- and T-cell clonality assay system is a sensitive and specific tool useful for rapid identification of clonal lymphocyte populations and will likely have broad clinical applications.

B-Lymphocytes↗

A new strategy for treating nets. Part 1: formulation and dosage.

The conventional dosages of pyrethroid insecticides on mosquito nets assume that nets will be retreated at 6-12 month intervals. However, dosage should be related to washing of nets; if nets are only washed once or twice a year, their dosage requirements will be different to those which are washed fortnightly. A 'low-dose, frequent-wash' retreatment system might be technically more appropriate and more affordable where nets are washed frequently, as they are in Dar es Salaam. Moreover, for use as a domestic insecticide, water-based formulations of pyrethroid are preferable to the more commonly used emulsifiable concentrates (ECs). This paper reports laboratory evaluations of three formulations (ECs, Flowable, CS) of three pyrethroids (deltamethrin, lambdacyhalothrin, permethrin). Insecticidal activity was tested using serial bioassays at a range of dosages using Anopheles gambiae. The water-based formulations were no less effective than the ECs, even at the lowest dosages. Nets treated with 3 mg/m2 and then repeatedly washed and retreated after each wash with either 3 mg/m2 or 1 mg/m2 were subjected to gas chromatography analysis. This showed that the amounts of pyrethroid in the nets accumulated rapidly over the first few wash-retreatment cycles and then remained fairly stable over subsequent cycles. These nets gave consistently high bioassay mortalities throughout the experiment, while the mortality declined rapidly after several washes with the nets that were treated at 3 mg/m2 but not retreated. Experimental huts were used to compare the effectiveness of these 2 net retreatment regimes and nets which were not retreated. All nets caused high mortality rates amongst Anopheles females, but had negligible effects on culicines; either in killing them or in preventing feeding. Therefore use of a high 'loading' dose for initial treatment with lower 'maintenance' doses for retreatment may be preferable to ensure that net users promptly perceive the benefits of the insecticide against culicines.

Animals↗

A new strategy for treating nets. Part 2: users' perceptions of efficacy and washing practices and their implications for insecticide dosage.

The conventional way to treat a mosquito net with pyrethroid insecticide is to apply a standard dosage every 6-12 months, and to avoid washing the net until just before retreatment. In some places, nets are normally washed much more often than this, and it may then be more appropriate to apply smaller amounts of insecticide after each wash. The choice of strategy must take into account not only biological effectiveness, but also users' perceptions of this effectiveness and their net-washing habits. We used focus groups to compare users' responses to nets treated with different dosages and chemicals. One hundred current net users in urban Dares-Salaam were each given a net that had been pretreated either with permethrin (200 or 500 mg/m2), or with lambdacyhalothrin (3 or 15 mg/m2), or with water. Neither participants nor investigators knew which group had received which treatment. Focus group discussions were held after 2, 8 and 12 weeks. Participants greatly preferred treated nets. Low doses were perceived to be less effective, especially after 8 and 12 weeks. After 12 weeks most participants had washed their nets, despite requests to the contrary Dirty nets were regarded as unhealthy and socially unacceptable. Few participants experienced side-effects or expressed fears about the safety of treatment. We conclude that asking people to refrain from washing their nets is unrealistic. A 'low-dose frequent-treatment' strategy of insecticide application may be more appropriate in the long run. At first, however, low doses give perceptibly inferior protection. An initial high (loading) dose, followed by frequent lower (maintenance) dosages, might solve this problem.

Adolescent↗

Notification of real-time clinical alerts generated by pharmacy expert systems.

We developed and implemented a strategy for notifying clinical pharmacists of alerts generated in real-time by two pharmacy expert systems: one for drug dosing and the other for adverse drug event prevention. Display pagers were selected as the preferred notification method and a concise, yet readable, format for displaying alert data was developed. This combination of real-time alert generation and notification via display pagers was shown to be efficient and effective in a 30-day trial.

Clinical Pharmacy Information Systems↗

Can anything be done to maintain the effectiveness of pyrethroid-impregnated bednets against malaria vectors?

Pyrethroid-treated bednets are the most promising available method of controlling malaria in the tropical world. Every effort should be made to find methods of responding to, or preventing, the emergence of pyrethroid resistance in the Anopheles vectors. Some cases of such resistance are known, notably in An. gambiae in West Africa where the kdr type of resistance has been selected, probably because of the use of pyrethroids on cotton. Because pyrethroids are irritant to mosquitoes, laboratory studies on the impact of, and selection for, resistance need to be conducted with free-flying mosquitoes in conditions that are as realistic as possible. Such studies are beginning to suggest that, although there is cross-resistance to all pyrethroids, some treatments are less likely to select for resistance than others are. Organophosphate, carbamate and phenyl pyrazole insecticides have been tested as alternative treatments for nets or curtains. Attempts have been made to mix an insect growth regulator and a pyrethroid on netting to sterilize pyrethroid-resistant mosquitoes that are not killed after contact with the netting. There seems to be no easy solution to the problem of pyrethroid resistance management, but further research is urgently needed.

Animals↗

A comparative study of in vivo mutation assays: analysis of hprt, lacI, cII/cI and as mutational targets for N-nitroso-N-methylurea and benzo[a]pyrene in Big Blue mice.

We have compared the response of the native hprt gene and the lacI, cII, and cI transgenes in Big Blue B6C3F1 mice following treatment with either N-nitroso-N-methylurea (MNU) or benzo[a]pyrene (BaP). Three weeks after mutagen treatment splenic T cells were isolated from the animals, and samples were either cultured to measure mutation at the native hprt locus or used to extract genomic DNA for transgene mutation analysis. Phage rescued from extracted DNA were plated in the presence of 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (X-gal) to score lacI mutations, or plated on a hflAB lawn to score cII and cI mutants. With MNU hprt mutant frequency increased in a dose-related, sublinear manner up to 78-fold above background at the highest dose tested (20 mg/kg). In comparison, the lacI transgene yielded only a 3.1-fold increase at this dose, and the cII and cI transgenes did not show any increase. With 150 mg/kg BaP a 5.8- and 8.7-fold increase in mutant frequency was observed at hprt and lacI, respectively, while only a 1.3-fold increase was observed at cII. DNA sequencing revealed an increase in GC-->TA transversions among the cII mutants, suggesting that the increase was related to BaP exposure. No significant increase in cI mutant frequency was observed. Therefore, the order of mutation assay sensitivity was hprt>lacI>cII/cI with MNU, and hprt approximately lacI> cII/cI with BaP. While the hflAB selection system offers significant advantages with respect to cost and effort when compared to the lacI assay, additional evaluation of its sensitivity is warranted.

Animals↗

DNA synthesis inhibition as an indirect mechanism of chromosome aberrations: comparison of DNA-reactive and non-DNA-reactive clastogens.

Positive results in the in vitro assay for chromosome aberrations sometimes occur with test chemicals that apparently do not react with DNA, being negative in tests for mutation in bacteria, for DNA strand breaks, and for covalent binding to DNA. These chromosome aberrations typically occur over a narrow concentration range at toxic doses, and with mitotic inhibition. Indirect mechanisms, including oxidative damage, cytotoxicity and inhibition of DNA synthesis induced by chemical exposure, may be involved. Understanding when such mechanisms are operating is important in evaluating potential mutagenic hazards, since the effects may occur only above a certain threshold dose. Here, we used two-parameter flow cytometry to assess DNA synthesis inhibition (uptake of bromodeoxyuridine [BrdUrd]) associated with the induction of aberrations in CHO cells by DNA-reactive and non-reactive chemicals, and to follow cell cycle progression. Aphidicolin (APC), a DNA polymerase inhibitor, induces aberrations without reacting with DNA; 50 microM APC suppressed BrdUrd uptake during a 3-h treatment to <10% of control levels. Several new drug candidates induced aberrations concomitant with marked reductions in cell counts at 20 h (to 50-60% of controls) and suppression of BrdUrd uptake (<15% of control). Several non-mutagenic chemicals and a metabolic poison, which induce DNA double strand breaks and chromosome aberrations at toxic dose levels, also suppressed DNA synthesis. In contrast, the alkylating agents 4-nitroquinoline-1-oxide, mitomycin C, methylnitrosourea, ethylnitrosourea, methylmethane sulfonate and ethylmethane sulfonate, and a topoisomerase II inhibitor, etoposide, produced many aberrations at concentrations that were less toxic (cell counts >/=73% of controls) and gave little inhibition of DNA synthesis during treatment (BrdUrd uptake >/=85% of controls), although cell cycle delay was seen following the 3-h treatment. Thus, inhibition of DNA synthesis at the time of treatment is supporting evidence for an indirect mechanism of aberrations, when there is no direct DNA reactivity.

Animals↗

Epidemiology of gastrointestinal nematode parasitism in Suffolk and Gulf Coast Native sheep with special emphasis on relative susceptibility to Haemonchus contortus infection.

An eight-year study was conducted to define the epidemiology of gastrointestinal nematode infection in Suffolk and Gulf Coast Native (Native) breeds of sheep, and to determine if the Native sheep is more resistant to infection. For the initial three years, each breed grazed separate pastures where anthelmintic treatments were administered to individual animals on a salvage basis. For the last five years, both breeds grazed concurrently; anthelmintic treatments were administered to individual animals on a salvage basis for the first three years, and to all animals, when treatment criteria were met, for the last two years. The fecal egg count (FEC) and blood packed cell volume (PCV) were monitored, and tracer lamb nematode burdens were determined. Overall, FEC for both breeds increased in the spring (periparturient rise) for most years and in the summer for all years. Under separate grazing conditions, Native ewes and lambs had consistently lower infection levels than Suffolk ewes and lambs. During the haemonchosis season (June-September) each year, Suffolk ewe and lamb PCV decreased, and Native ewe and lamb PCV remained relatively stable. The salvage treatment protocol resulted in 27 treatments for Suffolk and one for Native ewes; similarly for lambs, 13 for Suffolk and zero for Native. Tracer lambs grazed with their respective breed, and the FEC and mean total nematode burden corresponded with the pattern of infection for their respective breed. The predominant nematodes found in Suffolk and Native tracer lambs were Haemonchus contortus and Trichostrongylus spp., respectively. Under concurrent grazing conditions, the same seasonal repeatable pattern of infection was present and was exhibited by both breeds, with the Native ewes and lambs being consistently and significantly (p < or = 0.05) lower for FEC and higher for PCV. The salvage treatment protocol resulted in 57 and zero treatments for Suffolk and Native ewes, respectively; for lambs, 46 and 11. Tracer lamb nematode burdens again corresponded to their respective breed pattern of infection, with H. contortus and Trichostrongylus spp. being predominant in Suffolk and Native lambs, respectively. Data from all tracer lambs showed a relatively low level of hypobiosis (H. contortus only), and, although there was no consistent hypobiosis season, the tendency was for a higher level to occur in the fall. These results showed that the classic repeatable seasonal pattern of gastrointestinal nematode infection occurred in both breeds of sheep, and that Native sheep were more resistant to infection (specifically H. contortus) than Suffolk sheep.

Animal Feed↗

Biliary pancreatitis: the era of laparoscopic cholecystectomy.

OBJECTIVE: To evaluate the efficacy and safety of a combined approach to the treatment of biliary pancreatitis using laparoscopic cholecystectomy and selective endoscopic retrograde cholangiopancreatography (ERCP). DESIGN: Consecutive case series. SETTING: Tertiary care center. PATIENTS: All patients undergoing primary operations for biliary pancreatitis during 2 time periods were included. In the open era (June 1982 through May 1988), there were 276 patients; in the laparoscopic era (January 1996 through June 1997), there were 114 patients. INTERVENTIONS: Open cholecystectomy with or without common bile duct exploration (CBDE); laparoscopic cholecystectomy with selective ERCP and/or laparoscopic CBDE. MAIN OUTCOME MEASURES: Two periods were compared for morbidity, mortality, the duration of preoperative and postoperative stays, and the total length of hospitalization. RESULTS: Both groups were demographically similar and had the same mortality (1.9%). Laparoscopic cholecystectomies provided a preoperative stay comparable to open cholecystectomy (6.4 vs 5.8 days), a shorter postoperative stay (1.5 vs 8.5 days), a lower incidence of CBDE (6.6% vs 26%), and a lower morbidity (8% vs 13.7%). The addition of an ERCP to laparoscopic cholecystectomy was associated with prolongation of the preoperative stay (7.4 vs 5.0 days), a comparable postoperative stay, a lower conversion rate (7.5% vs 13%), and fewer CBDEs (3% vs 13%). In 27 (42%) of the 64 ERCP cases, no stones were found. CONCLUSIONS: Treatment of biliary pancreatitis with combined laparoscopic cholecystectomy and selective ERCP is safe and effective and is associated with a shorter hospitalization and fewer CBDEs than open cholecystectomy. Unnecessary ERCPs can be reduced by improved selection criteria or greater dependence on operative CBDE.

Adult↗

Urinary bombesin-like peptide levels in infants and children with bronchopulmonary dysplasia and cystic fibrosis.

Compared to normal infants and children, there are increased numbers of neuroendocrine cells with bombesin-like peptide (BLP) immunostaining in the lungs of infants and children with bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF). However, there are no data documenting levels of urinary BLP in normal infants and children, or in children with lung disease. We therefore determined the normal developmental pattern for urinary BLP excretion in healthy infants and children, and in infants and children with BPD and CF, and correlated these findings with the subjects' clinical course. We measured urinary BLP levels in 110 subjects: 54 controls, 33 with BPD, and 23 with CF. An age-dependent decline in urinary bombesin levels was evident in the control and BPD subjects, but not in those with CF. There were no statistically significant differences in BLP levels between normal infants and those with BPD. Mean BLP levels were higher in the more immature preterm infants with BPD who required increased ventilatory support. The highest mean BLP levels were documented in BPD infants under age 3 months (882 fmol/mg creatinine), in controls between 3 and 12 months of age (625 fmol/mg creatinine), and in 12-60-month-old CF subjects (486 fmol/mg creatinine). Thus there is an age-dependent decline in BLP levels in controls and BPD, but not in CF. We speculate that the elevated urinary BLP levels in infants and children with BPD and CF may reflect increased pulmonary neuroendocrine cell activity in these conditions, due to the epithelial regenerative response to airway damage and repair.

Aging↗

Developmental screening scores among preschool-aged children: the roles of poverty and child health.

OBJECTIVES: To investigate, using a nationally representative sample of preschool-aged children, the relationship among poverty history, child health, and risk of an abnormal developmental screening score. METHODS: Data were derived from the 1988 National Maternal and Infant Health Survey and 1991 Longitudinal Follow-up. Family income in the child's prenatal year and at 2 years old defined a poverty history for each child. Multivariate logistic regression was used to estimate the effects of poverty history on risk of an abnormal screening score or delays in large-motor, personal-social, or language subscales. RESULTS: Poor and near-poor children were 1.6 to 2.0 times as likely as nonpoor children to be classified as abnormal, even when maternal and household characteristics and the child's health history were taken into account. Preterm birth, chronic illness, dearth of reading materials in the home, and maternal depression were also associated with elevated risks of abnormal scores. CONCLUSIONS: Poverty is the largest single predictor of an abnormal developmental screening score. The implications of inadequate medical care among poor children for the interpretation of individual screening scores and for amelioration of problems are also discussed.

Child Health Services↗

Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus.

Human serum paraoxonase (PON1) is located on high density lipoprotein and has been implicated in the detoxification of organophosphates and possibly in the prevention of low density lipoprotein lipid peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine (A genotype) and arginine (B genotype) at position 192 and the other leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effect of these polymorphisms on serum PON1 activity and concentration in 252 non-insulin dependent diabetes mellitus (NIDDM) individuals and 282 non-diabetic controls. Serum PON1 activity in the controls (214.6 nmol/min per ml (26.3-620.8)) was significantly higher than in NIDDM (158.7 nmol/min per ml (3.6-550.5) (P < 0.001) as was serum PON1 concentration (89.1 microg/ml (16.8-527.4)) compared to 76.7 microg/ml (3.6-443.8) (P < 0.01). In the control population MM homozygotes had significantly lower serum PON1 activity regardless of the 192 polymorphism whereas in NIDDM both LM and MM genotypes had lower serum PON1 activity than LL homozygotes only when the 192 AA genotype was present. Serum PON1 concentration was lower in NIDDM with AA/LM, AA/LL, AB/LL and AB/MM genotypes than in controls. Differences in PON1 activity were the major cause of differences in specific activity between genotypes. Neither the PON1 55 or 192 polymorphisms consistently influenced the serum lipid or lipoprotein concentrations in either population. Low serum PON1 activity in NIDDM may be related to an increased tendency to lipid peroxidation and may also increase susceptibility to toxicity from organophosphate exposure. Our findings thus raise the possibility that PON1 may be of importance in both the genetic and acquired predisposition to premature atherosclerosis and neuropathy in diabetes.

Adult↗

Bladder petechiae after cystoscopy and hydrodistension in men diagnosed with prostate pain.

PURPOSE: We determined if men with prostate pain syndromes have petechiae in the bladder after hydrodistension. MATERIALS AND METHODS: A total of 60 men with the diagnosis of prostate pain and without bacteriuria underwent cystoscopy and hydrodistension under a general or regional anesthetic. RESULTS: Of the 60 men 35 (58%) had moderate to severe petechiae similar in appearance to women with interstitial cystitis after hydrodistension. Men with moderate to severe bladder petechiae had fewer leukocytes in expressed prostatic secretions, smaller bladder capacities and less often testicular pain than men with more normal appearing bladders after hydrodistension. Symptomatic improvement 2 to 6 weeks after hydrodistension was more common in men with moderate to severe petechiae than in those with fewer petechiae. Absence of rectal pain predicted symptomatic improvement after hydrodistension. CONCLUSIONS: We suggest that bladder petechiae, and possibly interstitial cystitis or a related condition, may be more frequently associated with prostate pain syndromes in men than previously appreciated.

Adult↗

Biomedical risk factors for hospital admission in older adults.

OBJECTIVES: This study examines the influence of risk factors such as cigarette smoking, blood pressure, serum cholesterol, or chronic illness on frequency of hospital admission in a population-based sample. METHODS: Data from the National Health and Nutrition Examination Survey I Epidemiologic Followup Study for 6,461 adults aged 45 years and older were used to assess the influence of risk factors measured by interview, physical examination, and laboratory tests on frequency of hospital admission over a 12- to 16-year follow-up period. Cox proportional hazard regressions were estimated separately for men and women and for ages 45 to 64 years and 65 years and older. SUDAAN software was used to correct for clustering, stratification, unequal weighting, and multiple observations per respondent. RESULTS: Risk of hospitalization was higher for current but not former smokers (relative risk [RR] = 1.17-1.34 for different age-sex groups; P < 0.01), higher blood pressure (RR = 1.25-1.28 for ages 45-64; RR = 1.07-1.15 for ages 65 and older; P < 0.01), and lower serum albumin (RR = 1.08-1.14; P < 0.01). Diabetes, lung conditions, heart attack, and ulcer each were associated with higher risk in at least three of the four age-sex groups, as was arthritis among the middle-aged (45-64 years). Serum cholesterol was not associated with hospitalization. CONCLUSIONS: Chronic conditions with high morbidity as well as many factors associated with mortality are associated with a higher frequency of hospitalization.

Age Factors↗