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Biomedical subjects

R H Miller

Publications and source records attributed to R H Miller.

At least 109 records · Page 6Linked to original sources

Comparison of lipid composition of milk from half-Danish Jersey cows and United States Jersey cows.

We studied differences in lipid composition of milk from Jersey cows with US sires and from Jersey cows with Danish sires. Milk samples were obtained on DHIA test day from 32 cows with Danish sires and 32 herdmates with US sires in two herds. The Jerseys with US sires were paired with those with Danish sires by parity and stage of lactation. Mean percentage of milk fat was 5.7%, for Jerseys with Danish sires and 4.8% for Jerseys with US sires. Total fat per day was the same (.91 kg) for both groups. Detailed analysis of milk lipids indicated that lipid composition of milk was similar for cows with US sires and those with Danish sires. However, milk from Jerseys with Danish sires contained more free cholesterol than milk from Jerseys with US sires, 17.5 versus 14.3 +/- .6 mg/dl. The proportion of polyunsaturated fatty acids was greater for milk from Jerseys with US sires than for milk from Jerseys with Danish sires (2.3 vs. 2.1%). Although lipid composition of milk from both groups was generally similar, the milk of Jersey cows with Danish sires had higher concentrations of free cholesterol and lower proportions of polyunsaturated fatty acids, both of which are possible negative factors for health of consumers.

Animals↗

Variation in distances among teats of Holstein cows: implications for automated milking.

Distances among teats were measured immediately prior to and immediately following milking in 912 lactations of 506 Holstein cows to assess variation due to age (parity), stage of lactation, year, and observer. Data were used to simulate success or failure to attach by the Gascoigne Melotte robotic milker. Distance between front teats premilking was nearly twice that for rear teats. When attachment of the cluster to an udder with a particular set of teat distances was simulated, excessive distance between front teats was the most frequent cause of attachment failure for third and later parities. For first parity, extremely narrow distance between rear teats was the most frequent cause of predicted attachment failure. Reduction in teat distances because of milking was proportionately much greater for distance between rear teats (45 to 50%) than for other teat distances (25 to 29%). In a study of 10 Holstein cows measured at milking and at 0, 6, 8, and 12 h after milking, distances among teats increased linearly with time elapsed postmilking. Electronic storage of a profile of a cow for teat distance and adjustments for milking interval and stage of lactation can increase chances for successful cluster attachment.

Animals↗

The association of gastroesophageal reflux and otolaryngologic disorders.

The laryngeal manifestations of GER may present with a number of nonspecific signs or symptoms. Patients with hoarseness, dysphagia, globus sensation, laryngeal granulomas, and subglottic stenosis should be evaluated for GER. In addition, physicians should be aware of the possible association of GER with Zenker's diverticulum and laryngeal carcinoma. While pH manometry is the mainstay for diagnosis of GER, the sensitivity is lower for patients with head and neck manifestations of GER probably because of the intermittancy of the reflux. The use of a pharyngeal probe may improve the sensitivity of the test. Treatment of head and neck manifestations of GER is no different than reflux esophagitis and medical therapy is typically successful in resolving symptoms.

Carcinoma↗

Laryngeal preservation.

Laryngeal cancer represents a major medical problem in this state. While early stage tumors are treatable with relatively low morbidity or quality of life sacrifices, advanced stage disease requires a total laryngectomy with its inherent life-style negatives. Recent advances in chemotherapy protocols, specifically induction cisplatin and 5-fluorouracil followed by radiation therapy, have ushered in the era of larynx preservation. This has apparently been accomplished without a sacrifice in survival. While these protocols are experimental, patients may be offered this option at certain centers, and prospective accrual will be important to the long-term efficacy questions of such therapy. The historical background and scientific foundations of laryngeal preservation protocols are discussed, and the relevant trials reviewed. Moreover, specific management issues are covered, and finally, current and future questions of such therapy are explored.

Antineoplastic Combined Chemotherapy Protocols↗

Genetic heterogeneity of the hepatitis C virus.

Hepatitis C virus (HCV) is an important etiological agent in the development of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The virus, identified only recently, contains a single-stranded RNA genome of positive polarity, is distantly related to pestiviruses and flaviviruses, and has been classified as the first member of a third genus within the family Flaviviridae. Extensive analysis of HCV genomic sequences demonstrated that this virus possesses significant genetic heterogeneity. Different regions of the viral genome demonstrate a varying degree of heterogeneity; the regions coding for the putative envelope proteins are the most variable sites between different isolates. Furthermore, HCV circulates as a quasispecies in the host. During the course of acute and chronic infection, the sequence composition of the HCV population in one patient has been found to change sequentially with an extremely high rate of nonconserved nucleotide changes in the hypervariable region I (HVR1) of HCV. Such sequence changes alter the antigenicity of the epitopes coded within HVR1 so that these are not always recognized by preexisting antibodies. It has been suggested that this could represent one mechanism by which HCV evades host immune surveillance and may account for the high rate of chronicity observed in such infections. Continuous viral replication may, in turn, lead to the development of chronic liver disease, including HCC, in infected individuals. To date, at least nine major genetic groups (genotypes 1-9) and more than 30 subgroups of HCV have been recognized based on genetic differences. A distinct difference has been observed in the genotype distribution in Africa compared with other continents. Recent data have suggested a difference in pathogenesis and in the outcome of interferon therapy in individuals infected with HCV of certain genotypes. For example, genotype 1b (II) seems to be associated with more severe liver disease, including HCC, and with a poorer response to interferon therapy. The extensive genetic heterogeneity of HCV may have serious implications for the diagnosis, treatment and prevention of hepatitis C as well as in understanding the biology of infection by this important human pathogen.

Genome, Viral↗

Analysis of the X gene promoter of woodchuck hepatitis virus.

During the course of woodchuck hepatitis virus (WHV) replication three virus-specific mRNA transcripts that encode four essential proteins are produced. The transcripts are 3.6, 2.3, and 0.7 kb in size. The 3.6-kb transcript serves as the replicative intermediate as well as the template for translation of the nucleocapsid and polymerase proteins. The 2.3-kb mRNA serves as the template for translation of the virus envelope proteins. Both the 3.6- and 2.3-kb transcripts are polyadenylated and are readily found in the cytoplasm of infected hepatocytes. However, the 0.7-kb transcript, specific for the X gene, accumulates in the nucleus of infected cells and is polyadenylated poorly in hepatocytes. Thus, while it is likely that the 0.7-kb transcript is the template for translation of the X protein, it is possible that it also has a function at the RNA level to regulate virus replication or gene expression. In order to characterize the WHV X promoter we cloned the region of the WHV8 genome encompassing the viral enhancer through the amino terminus of the X gene into the vector pSV0CAT. We transfected Huh-7 and WLC-3 cells with the WHV X promoter construct, along with a plasmid encoding human growth hormone to control for transfection efficiency, and assayed for the presence of chloramphenicol acetyl transferase activity. We found that the WHV X promoter was about one-half as active as the well-studied simian virus 40 early or Rous sarcoma virus promoters. Next, we made a series of 5' and 3' deletion mutants and mapped the WHV X promoter to a 21-nucleotide domain (1482-GGGGAAGCTGACGTCCTTTCC-1502) which is approximately 100 bp downstream of the corresponding promoter in hepatitis B virus. Further analysis, using oligonucleotide-directed mutagenesis, demonstrated that the essential nucleotides comprising the WHV X promoter are located in a 10-nucleotide domain near the initiation codon of the X gene. Mutation of either nucleotide T at position 1490 or G at position 1491 within this domain was sufficient to reduce the level of promoter activity by 100-fold. Thus, we have defined the important nucleotides within the promoter of the WHV X transcript which is a first step in understanding the role of this transcript in WHV replication and gene expression.

Animals↗

Sequence analysis of the core gene of 14 hepatitis C virus genotypes.

We previously sequenced the 5' noncoding region of 44 isolates of hepatitis C virus (HCV), as well as the envelope 1 (E1) gene of 51 HCV isolates, and provided evidence for the existence of at least 6 major genetic groups consisting of at least 12 minor genotypes of HCV (i.e., genotypes I/1a, II/1b, III/2a, IV/2b, 2c, V/3a, 4a-4d, 5a, and 6a). We now report the complete nucleotide sequence of the putative core (C) gene of 52 HCV isolates that represent all of these 12 genotypes as well as two additional genotypes provisionally designated 4e and 4f that we identified in this study. The phylogenetic analysis of the C gene sequences was in agreement with that of the E1 gene sequences. A major division in the genetic distance was observed between HCV isolates of genotype 2 and those of the other genotypes in analysis of both the E1 and C genes. The C gene sequences of 9 genotypes have not been reported previously (i.e., genotypes 2c, 4a-4f, 5a, and 6a). Our analysis indicates that the C gene-based methods currently used to determine the HCV genotype, such as PCR with genotype-specific primers, should be revised in light of these data. We found that the predicted C gene was exactly 573 nt long in all 52 HCV isolates, with an N-terminal start codon and no in-frame stop codons. The nucleotide and predicted amino acid identities of the C gene sequences were in the range of 79.4-99.0% and 85.3-100%, respectively. Furthermore, we mapped universally conserved, as well as genotype-specific, nucleotide and deduced amino acid sequences of the C gene. The predicted C proteins of the different HCV genotypes shared the following features: (i) high content of proline residues, (ii) high content of arginine and lysine residues located primarily in three domains with 10 such residues invariant at positions 39-62, (iii) a cluster of 5 conserved tryptophan residues, (iv) two nuclear localization signals and a DNA-binding motif, (v) a potential phosphorylation site with a serine-proline motif, and (vi) three conserved hydrophilic domains that have been shown by others to contain immunogenic epitopes. Thus, we have extended analysis of the predicted C protein of HCV to all of the recognized genotypes, confirmed the existence of highly conserved regions of this important structural protein, and demonstrated that the genetic relatedness of HCV isolates is equivalent when analyzing the most conserved (i.e., C) and the most variable (i.e., E1) genes of the HCV genome.

Amino Acid Sequence↗

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma. Development of an effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV.

Animals↗

Managed care plan performance since 1980. A literature analysis.

OBJECTIVE: To compare the health care utilization, expenditure, quality of care, and satisfaction since 1980 of enrollees in managed care and indemnity plans. DATA SOURCES AND STUDY SELECTION: Studies selected met the following criteria: data from 1980 forward, private insurance or Medicare enrollees, a comparison group, a reasonable attempt at statistical adjustment for noncomparable managed care and indemnity plan enrollees, and peer-reviewed findings (with two exceptions). Few studies on preferred provider organization plan performance met the selection criteria. DATA SYNTHESIS: Compared with indemnity plans, health maintenance organization plans had somewhat lower hospital admission rates, 1% to 20% shorter hospital length of stay, the same or more physician office visits per enrollee, less use of expensive procedures and tests, greater use of preventive services, mixed results on outcomes, and somewhat lower enrollee satisfaction with services but higher satisfaction with costs. The evidence does not support the hypothesis that prepaid group practice or staff model health maintenance organizations are more effective than individual practice association or network model health maintenance organizations. CONCLUSIONS: Although this literature analysis found several clear patterns of results, several factors, including unmeasured selection bias, diverse and rapidly changing health plans and local market conditions, and relatively few research results, suggest that generalizations must be made with caution.

Health Care Costs↗

Distribution and differentiation of A2B5+ glial precursors in the developing rat spinal cord.

In many regions of the rat central nervous system, oligodendrocytes develop from migratory A2B5+ precursor cells. In the rat spinal cord, during early embryonic development the capacity for oligodendrogenesis appears to be restricted to ventral regions of the spinal cord, while cultures of postnatal rat spinal cord contain a distinct population of A2B5+ astrocyte precursors. To determine if, as in other regions of the CNS, spinal cord A2B5+ cells give rise directly to oligodendrocytes and astrocytes, the initial distribution, and subsequent dispersion, proliferation, and differentiation of spinal cord A2B5+ cells have been examined in both explant and dissociated cell cultures. Spinal cord oligodendrocytes develop from A2B5+ cells. At E14, A2B5+ cells are restricted to ventral regions of the spinal cord and as development proceeds they become more uniformly distributed throughout the spinal cord. In explant cultures, greater than 95% of the explants that contain oligodendrocytes also contain A2B5+ cells and a proportion of mature oligodendrocytes retain detectable A2B5 immunoreactivity briefly on their surface. The maturation of spinal cord oligodendrocyte precursors occurs in a number of distinct stages characterized by the expression of O4 immunoreactivity, which first appears at E16, and GC immunoreactivity, which first appears at E18. As spinal cord oligodendrocyte precursors acquire O4 immunoreactivity they appear to lose the ability to proliferate in response to PDGF but retain the ability to proliferate in response to bFGF, suggesting that the control of proliferation of oligodendrocyte precursors is, in part, dependent on their maturational state. In the presence of high serum, spinal cord A2B5+ cells fail to develop in isolated E14 dorsal spinal cord cultures, while in ventral cultures they subsequently differentiate into A2B5+ astrocytes suggesting that A2B5+ astrocyte precursors are also initially ventrally located. Unlike oligodendrocyte differentiation, however, the differentiation of spinal cord A2B5+ cells into astrocytes is delayed in early embryonic-derived cultures compared to those from older animals. These observations suggest that local influences may regulate the timing of spinal cord A2B5+ astrocyte development, but not spinal cord oligodendrocyte development.

Animals↗

Otolaryngology residency and fellowship training. The resident's perspective.

Based on the success rate of US otolaryngology graduates on the American Board of Otolaryngology Certification Examination, it would appear that otolaryngology training is quite good. However, it is not clear that all aspects of training are equal in quality, not only between programs but also within a single program. One indication that there may be areas of weakness is the fact that despite the perceived national shortages of primary care physicians in the United States and the overabundance of specialists, 25% of the approximately 260 graduating otolaryngology residents extend their training beyond specialty training to subspecialty levels (Manpower Committee of the American Academy of Otolaryngology-Head and Neck Surgery, unpublished data obtained from chief resident questionnaires, 1990-1992). The most popular area of fellowship training is facial plastic surgery, followed by neurotology and head and neck oncology. Pediatric otolaryngology fellowships make up most of the balance. Most of the fellowships are well structured and are 1 year in duration. Others are more like apprenticeships and may be of shorter duration. A few are 2 years long and include a significant research commitment reserved for individuals entering academic practice.

Allergy and Immunology↗

Changes in human papillomavirus typing of recurrent respiratory papillomatosis progressing to malignant neoplasm.

A patient with recurrent respiratory papillomatosis progressed spontaneously to carcinoma resulting in death. Serial biopsy specimens obtained during a 9-year course of this patient's disease were tested via polymerase-chain reaction and Southern hybridization to detect the human papillomavirus (HPV) types present during the patient's course of disease. Early biopsy specimens were positive for HPV types 6 and 11. As atypia progressed to carcinoma, HPV types 6 and 11 remained present, but the signal decreased and HPV 16 became increasingly positive. The significance of these findings will be discussed.

Carcinoma, Squamous Cell↗

Recurrent respiratory papillomatosis: juvenile versus adult forms.

Recurrent respiratory papillomatosis (RRP) has been described to have a juvenile or aggressive form and an adult or less aggressive form. However, the aggressive form may occur in an adult and vice versa. Some authors have reported a quiescence in the juvenile form with the onset of puberty. In order to further characterize these two forms of RRP and to analyze the effects of puberty, we reviewed the records of 32 patients treated for RRP at our institution over a 10-year period. We found that the aggressive form typically occurs in the very youngest of patients (average of 2 years old as compared to an average of 17 years old in the less aggressive form). Although subglottic involvement universally occurred in our group with aggressive disease, approximately 40% developed subglottic disease very early as compared with 20% of patients with less aggressive disease. Additionally, our data do not support the theory of spontaneous regression with the onset of puberty. These and other findings will be discussed in detail. We also propose a new classification for RRP to eliminate confusion.

Adolescent↗

Crohn's disease of the larynx.

Extraintestinal involvement of Crohn's disease is becoming more readily identified. Laryngeal involvement by Crohn's disease, however, has been reported in only five cases in the medical literature. We present the sixth case as well as an analysis of the prior reports.

Adult↗

Role of the neutrophil leucocyte in the local and systemic reactions during experimentally induced E. coli mastitis in cows immediately after calving.

Mammary leucocytes are the major contributors to natural defence against mastitis after a microorganism has entered the gland. This paper reviews the role of the neutrophil granulocyte during acute coliform mastitis in cows in the periparturient period. Qualitative and quantitative aspects of several neutrophil cell functions before and during experimentally induced infections are briefly discussed.

Animals↗

Effects of pyruvate on the metabolism and insulin resistance of obese Zucker rats.

Female obese Zucker rats aged 5 wk were randomly assigned to a control diet or one of two experimental diets. Experimental diets contained 6% of energy as pyruvate in the form of calcium-pyruvate (Ca-pyr) or 6% pyruvylglycine (pyr-gly). Diets were pair-fed according to the experimental group with the lowest food consumption. During the 3 wk of dietary treatment, Ca-pyr- and pyr-gly-fed rats gained significantly less weight, had a lower food-conversion efficiency, and maintained a higher resting oxygen consumption (mL.min-1 x kg-0.67) than control rats. Ca-pyr and pyr-gly also lowered the respiratory exchange ratio of the rats resulting in a 90% increase in their lipid oxidation and a 50% decrease in their carbohydrate oxidation. Glucose tolerance, assessed by an oral glucose load, was not different among treatments, but the insulin response of the pyr-gly-fed rats was significantly less than that of the control rats despite elevated plasma triglyceride concentrations in the pyr-gly-fed rats (control, 1.43 +/- 0.16 vs pyr-gly, 3.76 +/- 0.87 mmol/L). These results suggest that pyr-gly, like Ca-pyr, favorably alters the metabolism of obese Zucker rats. In addition, pyr-gly appeared to reduce the insulin resistance that develops spontaneously in obese rats.

Analysis of Variance↗

Managed care plans: characteristics, growth, and premium performance.

Over the past dozen years, network-based managed care plans have undergone a remarkable transformation. At the beginning of the 1980s, managed care plans occupied a niche in a marketplace dominated by indemnity insurance plans. By 1993, managed care plans accounted for a growing majority of health plan enrollees. Moreover, enrollment in newer forms of managed care quickly surpassed that of the older group and staff model HMOs. Beginning as hybrids of elements of group and staff model HMO plans and of the old FFS system, these newer types of network-based plans have evolved as they have grown. Reacting to rapidly rising health care premium costs, employers wanted to move their employees and dependents relatively quickly into managed care plans. However, employers and enrollees were not prepared to make a rapid, wholesale shift from indemnity insurance and FFS towards the older, more restrictive type of group and staff model HMO plans. Moreover, intermediaries and providers were not prepared to accommodate such a shift, even if employers and employees wanted it to take place. Indeed, many of the major actors--employers, enrollees, health benefit intermediaries, physician networks, medical groups, hospitals and integrated delivery systems--have had to ascend very substantial managed care "learning curves". Although we have witnessed the overall movement of many enrollees from managed care plans that closely resembled the indemnity insurance plans toward plans with more similarities to the group and staff model HMOs, the extent of the changes has varied markedly among the dozens of local market areas, and even within local market areas. As the health care system evolves, the number and complexity of different types of contractual managed care relationships are increasing almost exponentially. The resulting difficulty in classifying managed care plans has implications for health services researchers. Increasingly, it is important to compare performance among health plans not at the level of the entire health plan, but at the level of the provider organizations or networks that actually provide health care services to enrollees. The Medical Outcome Study adopted this approach (12, 21, 35), providing useful insights into the dual effects of risk-sharing and provider organization on health care utilization, quality of care, and enrollee satisfaction. As well, if managed care plan classifications are to be meaningful, it is important to clearly specify the characteristics of the provider organization and the rest of the delivery system in whatever research is undertaken.(ABSTRACT TRUNCATED AT 400 WORDS)

Health Care Reform↗