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Biomedical subjects

J K Miller

Publications and source records attributed to J K Miller.

At least 19 recordsLinked to original sources

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent

Reactivation of latent herpes simplex virus by excimer laser photokeratectomy.

We tested whether excimer laser photorefractive and phototherapeutic keratectomy may reactivate latent herpes simplex and cause recurrent keratitis in mice. Two of ten latently infected mice that were treated with ten excimer laser pulses to the corneal epithelium shed herpes simplex virus type 1, as did four of ten mice that were treated with 50 excimer laser pulses. Ocular shedding of herpes simplex virus was detected in four of ten mice that were treated with ethylenediamine-tetraacetic acid (EDTA) scraping of the corneal epithelium without laser keratectomy, and in six of ten mice on which combined EDTA-facilitated epithelial removal was performed followed by the application of ten excimer laser pulses. In both EDTA-treated groups, viral shedding was prolonged and 18 of 20 mice developed marked corneal opacification or neovascularization, or both. Corneal photoablation with the excimer laser may induce reactivation of latent herpes simplex virus, even in mice with clear and smooth-appearing corneas, and should be considered in the differential diagnosis of humans with persistent corneal epithelial defects after refractive or therapeutic excimer procedures.

Animals

Addition of chloride to a prepartal diet high in cations increases 1,25-dihydroxyvitamin D response to hypocalcemia preventing milk fever.

In this study, we present evidence that cows fed highly cationic diets are less responsive to parathyroid hormone than those fed a highly anionic diet. Forty-seven Jersey cows (55 mo of age) were fed an alfalfa haylage-based diet supplemented with either anions (Cl-) or cations (Na+). Cows fed the high cationic diet suffered significantly more cases of milk fever (6 out of 23) than those fed the high anionic diet (1 out of 24). Concentrations of Ca at parturition and the first 2 d of lactation were significantly higher in cows fed the anionic diet. Secretion of parathyroid hormone in response to developing hypocalcemia was similar in cows fed either diet. Plasma hydroxyproline concentration (an index of bone Ca resorption activity) was greater in cows fed the anionic diet, suggesting better utilization of bone Ca. Plasma 1,25-dihydroxyvitamin D concentration was correlated inversely with plasma Ca and related directly to plasma parathyroid hormone in both groups of cows. However, the magnitude of the response (the amount of 1,25-dihydroxyvitamin D produced per unit increase in parathyroid hormone) was reduced greatly in cows fed the high cation diet. Because parathyroid hormone regulates both bone Ca resorption and renal 1,25-dihydroxyvitamin D production, these data suggest that prepartal diets high in cations decrease the ability of bone and renal tissues to respond to parathyroid hormone. Addition of anions to prepartal diets can reduce the excess cation balance of diets, increasing tissue response to parathyroid hormone and enabling the cow to better adapt to the Ca demands of lactation.

Animal Feed

Effect of wet or dry corn gluten feed on nutrient digestibility and milk yield and composition.

A 22-wk trial was conducted to determine variations in nutrient concentrations of wet and dry corn gluten feed and their effect on nutrient digestibility and milk yield and composition. Holstein cows (n = 48) were blocked at parturition by parity and assigned randomly within block to one of three diets. All cows were fed a control TMR containing corn silage, ground corn, and commercial concentrate plus 2.3 kg/d of alfalfa hay during the 2-wk adjustment period. Thereafter, control diet was fed as wet or dry corn gluten feed substituted for 27% of dietary DM supplied by the control diet. Each cow received TMR for ad libitum consumption. Variations in nutrient concentrations of corn gluten feed were observed throughout the trial. The coefficient of variation was highest for ADIN, and standard deviation was highest for NDF. Intake of CP and NDF and apparent digestibility of DM were greatest when wet or dry corn gluten feed was fed. No differences in DMI, milk yield, and percentages of milk protein, lactose, or SNF were observed, but milk fat percentage was lowest when dry corn gluten feed was fed. Results indicate that corn gluten feed can replace 27% of dietary DM without altering milk yield, but new deliveries should be sampled regularly and amounts fed adjusted to compensate for varying nutrient concentrations.

Animal Feed

A prospective analysis of inter-rater agreement between a physician and a physician's assistant in selecting QMR vocabulary terms.

We prospectively identified a cohort of 19 hospital inpatients to serve as a test set to determine the agreement between a physician and a physician's assistant in selecting and entering Quick Medical Reference (QMR) vocabulary terms for use in QMR case analysis mode. For positive findings, there was good agreement between data entered by the physician's assistant and data entered by the physician. Overall matches for positive findings were 0.66 concordance for the initial state, and 0.67 for the final state. Concordance for negative findings was substantially lower. The QMR generated differential diagnoses lists of the physician and physician's assistant were judged as similar in 14 (74%) of the 19 cases when QMR critique and assert functions were used.

Artificial Intelligence

Luque interpeduncular segmental fixation of the lumbosacral spine.

Interpeduncular segmental fixation of the lumbar and lumbosacral spine with Luque screws and plates is becoming increasingly popular. In this retrospective study, 52 consecutive patients treated with this technique were followed for 16 to 44 months (average, 21). Indications for surgical arthrodesis included lumbar instability from degenerative disease (16 cases), spondylolisthesis (25 cases), pseudarthrosis (eight cases), fracture (two cases), and tumor (one case). Fusion with instrumentation spanned one level in nine patients, two in 38 patients, three in four patients, and four in one patient. Patients wore a rigid lumbar orthosis for an average of six months (range, two to 16). Ten complications occurred in nine patients: two superficial wound infections, four neurologic complications, three loosened screws, and one broken screw. An overall fusion rate of 96% was achieved; pseudarthrosis is suspected in one case and failed arthrodesis secondary to trauma in a second patient. At four months postoperatively, solid unions had resulted in most of the cases, as seen roentgenographically. All patients reported decreased back pain; however, one patient is addicted to narcotics. Twenty-five of the 29 patients employed were able to return to work at an average of six months postoperatively.

Adolescent

Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection.

The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States.

Acute Disease

Structure of interleukin 1 alpha at 2.7-A resolution.

The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated alpha (IL-1 alpha) and beta (IL-1 beta), are produced by activated macrophages and other cell types. In an effort to understand the similarities and differences in the physicochemical and functional properties of these two proteins, a program was initiated to determine their structures. Crystals of IL-1 alpha were grown, and the three-dimensional structure at 2.7-A resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-1 alpha model has been performed as well. The overall structure is composed of 14 beta-strands and a 3(10) helix. The core of this structure is a capped beta-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1 beta [Priestle, J. P., et al. (1988) EMBO J. 7, 339-343] and soybean trypsin inhibitor (STI) [McLachlan, A. D. (1979) J. Mol. Biol. 133, 557-563]. In this paper, the overall structure of IL-1 alpha and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-1 beta and STI are made within these contexts.

Amino Acid Sequence

The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies.

To determine trends in the incidence and epidemiology of acute hepatitis B in the United States we conducted intensive surveillance for viral hepatitis in four sentinel counties from October 1, 1981, to September 30, 1988. The overall incidence of hepatitis B remained relatively constant throughout the study period (average, 13.2 cases per 100,000 population), but disease transmission patterns changed significantly. The proportions of hepatitis B cases accounted for by homosexual activity and health care employment decreased 62% and 75%, respectively; the proportions of cases accounted for by parenteral drug use and heterosexual exposure increased 80% and 38%, respectively. The percentage of patients for whom no risk factor was identified (30% to 40%) did not change over time. These patients tended to belong to minority populations, and their socioeconomic level was low. The decline in the number of hepatitis B cases among homosexual men probably results from the modification of high-risk sexual behavior; the decline among health care workers is due mostly to hepatitis B immunization. The current strategy for prevention of hepatitis B, which targets high-risk groups for immunization, has failed to have a significant impact on the incidence of disease.

Acute Disease

Patterns of organellar and nuclear inheritance among progeny of two geographically isolated strains of Volvox carteri.

Strains of Volvox carteri forma nagariensis derived from Japanese and Indian isolates ("J" and "I" strains, respectively) exhibited length differences (RFLPs) for approximately 90% of the restriction fragments detected by hybridization with a variety of unique-sequence, small-gene-family and repetitive-element probes, including heterologous probes of chloroplast and mitochondrial origin. Extensive post-zygotic mortality was observed among the zygotes produced by crossing J and I strains, suggesting some form of genetic incompatability between them. Most of the viable progeny exhibited recombinant patterns of nuclear inheritance and maternal inheritance of mitochondrial and chloroplast markers. However, many progeny exhibited exclusively uniparental (usually maternal, but in one case paternal) inheritance of both nuclear and organellar markers. Some of these non-recombinant individuals may be derived from "parthenospores" (dormant asexual cells resembling zygospores). Others may be a result of "pseudogamy," in which one of the parental pronuclei is excluded from the zygote, followed by selective exclusion of both the mitochondrial and the chloroplast genomes derived from that same parent. When segregation patterns for 44 nuclear markers were analyzed in 90 recombinant progeny, statistically significant, locus-specific deviations from expected Mendelian transmission ratios were observed for a sizeable fraction of all markers in both reciprocal crosses: some markers were preferentially transmitted by the J strain, while others were preferentially transmitted by the I strain. It is speculated that these transmission distortions may be related to the regions of inter-isolate genetic incompatibility, and may complicate the use of J x I crosses to establish a RFLP-based linkage map for the species.

Animals

Effects of hypomagnesemia on reactivity of bovine and ovine platelets: possible relevance to infantile apnea and sudden infant death syndrome.

Blood platelet function and possible involvement in death of hypomagnesemic ruminants was investigated with 26 Angus cows, 15 mature Hampshire wethers, eight Finnish-Hampshire ewes, and 36 growing Dorset lambs. Hypomagnesemia was induced by feeding vegetative spring tall fescue to 13 cows and semipurified diets low in Mg to nine wethers, four ewes, and 18 lambs. In comparison with controls, dietary treatments reduced plasma Mg concentrations 55% in cows, 36% in wethers, 66% in ewes, and 78% in lambs. Hypomagnesemia reduced in vitro reactivity of cow and lamb platelets to thrombin, ADP, and platelet active collagen, but in vitro tests may not accurately reflect in vivo platelet reactivity. Microscopic examination of platelet-rich plasma revealed a threefold increase in clumped platelets from four hypomagnesemic ewes compared to four normomagnesemic ewes. This suggests that in vivo activation and exhaustion of platelets may have contributed to reduced in vitro platelet reactivity. Six of 18 hypomagnesemic lambs died spontaneously in tetany after 2-12 months on low-Mg diets. Heart and lung lesions were markedly similar to pathological changes induced in other lambs by intravascular activation of platelets with 500 micrograms of vascular collagen fibrils per kg body weight injected intravenously. These results suggest the possibility of abnormal blood platelet activation as a significant mortality risk factor in severe hypomagnesemia.

Animals

The sharp theta rhythm on the occipital areas of prematures (STOP): a newly described waveform.

This study on 500 prematures and neonates with conceptional ages (CA) of 23-49 wks describes the STOP pattern (sharp theta on the occipitals of prematures). STOP is similar to PT theta (premature temporal theta) in configuration, but is faster in frequency, lower in amplitude, more often unilateral, aside from the obvious difference in location. The incidence (%) was highest at the youngest age, decreasing to zero near term, and the amount (number of bursts) was greatest at 25 wks (CA). Three different parts appear in the incidence and amplitude curves, and these three parts may be related to changes in the laterality of the pattern. In the youngest age these rhythms are mainly bilateral, in the older neonates they are unilateral and are either for the ages between those extremes. STOP is seen more often in active sleep, but is reduced in incidence in patients with abnormal slow waves, ictal or immature patterns. Right-sided STOP was more frequently associated with abnormal EEGs, especially in males with right-sided sharp waves, often noted in the patients with seizures and intraventricular hemorrhages.

Electroencephalography

Iodine in milk and meat of dairy cows fed different amounts of potassium iodide or ethylenediamine dihydroiodide.

Relationships between I intake by lactating Holstein cows and iodine concentrations in milk and meat were investigated. Six treatment groups with seven cows assigned to each treatment were fed a basal diet containing .8 mg I/kg alone or supplemented with I at 1, 2, or 4 mg/kg in four 5-wk periods. Basal alone was fed in the first and third periods and the I supplement was potassium iodide in the second period and ethylenediamine dihydroiodide in the fourth period. Iodine concentrations in milk increased with each increase in dietary I from 205 ng/ml for basal periods to 404, 477, and 757 ng/ml when 1, 2, or 4 mg/kg I was fed as potassium iodide; and 467, 535, and 869 ng/ml when 1, 2, or 4 mg/kg I was fed as ethylenediamine dihydroiodide. Concentrations of I in skeletal muscle after the fourth period were not affected by 2 mg/kg I and only increased from 166 to 199 ng/g when supplemental I was 4 mg/kg. Moderate changes in dietary I are quickly reflected in milk I, but I in meat is relatively stable.

Animals

Effect of magnesium administration route on plasma minerals in Holstein calves receiving either adequate or insufficient magnesium in their diets.

Rates of increase in plasma Mg following rectal or oral administration of solutions containing 30 g MgCl2.6H2O were compared in 10 Holstein bull calves receiving wheat straw (.07% Mg) and concentrates (.04 or .24% Mg) fed separately for ad libitum consumption. Treatments were administered in a sequence, which involved each calf with all combinations of MgCl2.6H2O dosing routes and dietary Mg within a 6-wk period. Plasma Mg concentration averaged 1.95 mg/dl initially but fell below 1 mg/dl within 2 wk after supplemental Mg was omitted. Maximum increases in plasma Mg concentration following oral or rectal dosing were 16 or 47% when dietary Mg was adequate and 48 or 124% when Mg was deficient. Calves fed either diet responded maximally to rectal infusion within 10 min, but plasma Mg of deficient calves increased throughout 160 min after oral dosing. Plasma Mg of deficient calves responded quicker and reached higher concentrations after rectal infusion, but the response was sustained longer after oral administration.

Administration, Oral

Importance of heterosexual activity in the transmission of hepatitis B and non-A, non-B hepatitis.

To identify previously unrecognized sources for acquiring acute hepatitis B and non-A, non-B (NANB) hepatitis, we interviewed patients with these types of hepatitis who were reported to two county health departments in the United States and matched control subjects for known and potential risk factors for acquiring hepatitis. Of 218 patients with hepatitis B and 140 patients with NANB hepatitis, 46% and 53%, respectively, had no commonly recognized source for infection. When these patients were compared with control subjects, significantly more patients with hepatitis B had multiple heterosexual partners, accounting for 14% of all hepatitis B infections; more patients with NANB hepatitis either had sexual or household contact with a person who had hepatitis in the past or had multiple heterosexual partners, accounting for 11% of all NANB infections. This is the first study to suggest that heterosexual transmission may play an important role in the spread of NANB hepatitis.

Adult

Influence of uvrB and pKM101 on the spectrum of spontaneous, UV- and gamma-ray-induced base substitutions that revert hisG46 in Salmonella typhimurium.

Oligonucleotide probes were used to identify base substitutions in 1089 revertants of hisG46 in Salmonella typhimurium that arose spontaneously or following irradiation with UV- or gamma-rays. The hisG46 allele, carrying a mutant CCC codon (Pro) in place of the wild-type codon CTC (Leu69) reverted via 6 distinguishable mutational events--C to T transitions at codon sites 1 or 2, C to A or C to G transversions at codon site 1, C to A at codon site 2, and an extragenic suppressor mutation. The distribution of hisG46 revertants differed among treatments and was influenced by the DNA-repair capacity of the bacteria. Plasmid pKM101 enhanced the frequencies of both spontaneous and induced mutations; transversion events were enhanced more efficiently by pKM101 than were transition events. Compared to Uvr+ bacteria, Uvr- bacteria had higher frequencies of spontaneous and induced mutations; transition mutations were enhanced more efficiently than were transversion mutations. The influence of DNA-repair activities on the mutational spectra provides some insights on the origins of spontaneous and UV-induced mutations.

DNA Damage

The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance.

The time course of diphenhydramine concentrations and effects on both mental performance and subjective feelings of drowsiness were assessed in 15 healthy men. Subjects received single oral doses of diphenhydramine, 50 mg, and placebo in this double-blind crossover study. Diphenhydramine plasma concentrations and central nervous system actions were assessed for 24 hours after each treatment. Cognitive impairment was assessed with an automobile driving simulator and digit symbol substitution scores, whereas drowsiness was self-assessed on a visual analog scale. Diphenhydramine produced significant feelings of drowsiness for up to 6 hours after the dose, whereas significant mental impairment was apparent for only 2 hours. Despite the difference in duration of these effects, drowsiness and mental impairment have parallel slopes when effects are related to diphenhydramine concentrations. These data suggest that although the apparent diphenhydramine concentration thresholds to produce drowsiness are lower (30.4 to 41.5 ng/ml) than those needed to produce mental impairment (58.2 to 74.4 ng/ml), these effects have profiles consistent with their being manifestations of the same pharmacologic effect.

Adult