Barbiturates in the care of the terminally ill.
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Biomedical subjects
Publications and source records attributed to K Nelson.
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OBJECTIVE: To examine the suitability of estradiol labeled with iodine I 123 at 16 alpha for imaging estrogen-receptor-positive breast carcinoma using imaging instrumentation that is widely available. DESIGN: Single-photon emission computed tomographic imaging survey of 29 women with suspected primary or expected recurrent breast carcinoma. SETTING: University-based referral center. PARTICIPANTS: Twenty-nine women undergoing diagnosis for primary or recurrent breast carcinoma. Selection was voluntary. MAIN OUTCOME MEASURE: Qualitative imaging study designed to provide tomographic data of radioligand retention and descriptive data of imaging results. RESULTS: Single-photon emission computed tomographic imaging using 123I-estradiol at 16 alpha was performed for patients with breast carcinoma. Independent readers, without knowledge of receptor status or proven disease, interpreted the films. Scintigraphic detection was most noteworthy in patients with chest wall tumors and inflammatory breast cancer. Agreement between readers was 98% for true-negative readings and 94% for true-positive readings, but only 60% for false-positive and false-negative film readings. CONCLUSIONS: Our results indicated that areas shown on imaging were also found to have estrogen-receptor activity and that radioligand accumulation can occur with low frequency in some surgically explored tissue. Radioligand imaging with 16 alpha-123I-estradiol can locate estrogen-receptor-positive breast tumors, including some that may be difficult to detect using conventional diagnostic imaging.
The main thrust of this paper is to question whether in earlier studies the 'motherese hypothesis' has been adequately tested. The present study first explores concurrent relations between maternal and child language at an early age, using the Snyder, Bates & Bretherton (1981) questionnaire to assess vocabulary at 1;1. With a large sample of 45 subjects, videotaped at 1;1 and 1;8, it was possible to analyse earlier talkers separately from later talkers. The results indicate pre-existing differences between the mothers of earlier and later talkers as early as 1;1--some 5 months before other studies have examined the possible facilitative effects of 'motherese'. Secondly, and perhaps more importantly, when the sample was divided according to stylistic preference at 1;8, several associations between maternal language at 1;1 and MLU at 1;8 emerged for the non-expressive group which were non-existent for the expressive group. These results imply that earlier studies may have been looking for the effectiveness of maternal input too late. Moreover, it may continue to be difficult to demonstrate consistent effects of child-directed speech as long as researchers continue to ignore individual differences in style of language acquisition.
Many theories of grammatical and lexical acquisition assume that children learn predominantly nouns, and specifically names of objects, when they first begin to acquire words in the second year. We show that the noun bias in early vocabularies is far from universal, and that it rests only in part on the acquisition of object names. An analysis of vocabulary composition from 45 children at 1;8 indicates that more nouns are acquired than all other word classes, but that of the nouns acquired only about half are the names of basic level object classes (BLOCs). An examination of the use of nouns in mother-child discourse shows that non-object words referencing locations, actions and events, for example, are used in distinctive pragmatic and grammatical contexts which might enable a child to grasp the word's use and eventually its meaning. It is concluded that a theory of lexical acquisition in discourse context is required to explain word learning at all levels and for all word types. Implications for semantic bootstrapping theories are considered.
The Multicenter AIDS Cohort Study (MACS) was designed to study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, including the relationship between hepatitis B virus (HBV) and HIV-1 infection. In total, 4954 homosexual men were recruited from April 1984 through March 1985 and have been followed up thereafter every 6 months. Hepatitis B surface antigen and hepatitis B core antibody were tested for at the first visit by RIA or EIA; HIV-1 antibody testing was done at each visit by ELISA and confirmed by Western blot assay. The role of HBV infection in HIV-1 seroconversion was studied by stratification for sexual behavior and disease visit by visit. The adjusted risk ratio was 2.02 for hepatitis B surface antigen carriers and 2.14 for hepatitis-immune cases compared with hepatitis B-susceptible subjects. Similar results were obtained using a logistic regression model. After taking into account changes in sexual behavior and disease over time, the authors conclude that past HBV infection remains suspect as a cofactor or as a surrogate for other factors associated with HIV-1 seroconversion.
In an effort to understand the molecular genetic basis of temporal variation in frequency and severity of bacterial disease, genetic relationships among strains of Streptococcus pyogenes that caused scarlet fever epidemics in Canada in the early 1940s and in eastern Germany in the 1960s to 1980s were studied. Application of multilocus enzyme electrophoresis and comparative sequencing of the gene (speA) encoding streptococcal pyrogenic exotoxin A (scarlet fever toxin) revealed that new waves of scarlet fever are associated with an increase in frequency of S. pyogenes clones carrying variant speA alleles. This finding suggests that the occurrence of new scarlet fever epidemics can be predicted by comprehensive monitoring of the frequency of S. pyogenes clones with variant toxin alleles.
Patterns of mitochondrial DNA (mtDNA) variation were examined in 133 mole-rats constituting all four chromosomal species (2n = 52, 2n = 54, 2n = 58, and 2n = 60) of the Spalax ehrenbergi superspecies in Israel, as well as the peripheral isolates of 2n = 60. In the main range of the complex, a total of 28 mtDNA haplotypes were found in 64 mole-rats, with most haplotypes being unique to either a single chromosomal species or population. mtDNA divergence increased from low to high diploid number in a north-to-south direction in Israel. Overall levels of mtDNA diversity were unexpectedly the highest in the 2n = 60, the youngest species of the complex. The mtDNA haplotypes can be separated into two major groups, 2n = 52-54 and 2n = 58-60, and a phylogenetic analysis for each group revealed evidence of a few haplotypes not sorted by diploid number. The overall patterns of mtDNA divergence seen within and among the four chromosomal species are consistent with the parapatric mode of speciation as suggested from previous studies of allozyme and DNA hybridization. In a separate data set the patterns of mtDNA variation were examined across the main geographic range and across peripheral semi-isolates and isolates of the 2n = 60 chromosomal species. Fifteen haplotypes were found in 69 mole-rats. High levels of mtDNA diversity characterized the main range, semi-isolated, and even some desert isolated populations. The peripheral isolates contain much mtDNA diversity, including novel haplotypes.
A reference collection of 72 strains representing 37 serovars of Salmonella subspecies I has been established for use in research on genetic and phenotypic variation in natural populations. Included are isolates of the host-adapted serovars S. choleraesuis, S. dublin, S. gallinarum, S. paratyphi A, S. paratyphi B, S. paratyphi C, S. pullorum, S. sendai, S. typhi and S. typhisuis, as well as strains of S. enteritidis, S. typhimurium, and other commonly recovered serovars with broad host ranges. The isolates were characterized by enzyme electrophoresis for allelic variation in 25 chromosomal genes and represent 71 distinctive multilocus genotypes (electrophoretic types or ETs). Genetic relationships among the ETs are indicated in an evolutionary tree constructed by the neighbour-joining method from a matrix of Nei's standard genetic distance.
Multilocus enzyme electrophoresis was employed to estimate chromosomal genotypic diversity and relationships among 131 isolates of the non-motile Salmonella biotypes Gallinarum and Pullorum (serotype 1, 9, 12:-:-) that cause fowl typhoid and pullorum disease, respectively. Thirteen electrophoretic types (ETs), marking clones, were distinguished, and construction of a neighbour-joining phylogenetic tree revealed three lineages: one consisted of five ETs of Gallinarum, a second included seven ETs of Pullorum, and a third was represented by a single ET (Ga/Pu 1) that is intermediate between those of the other two lineages in both multilocus enzyme genotype and biochemical properties. Enzyme genotype analysis and comparative nucleotide sequencing of the phase 1 flagellin gene (fliC), the hook-associated protein 1 gene (flgK), and the 6-phosphogluconate dehydrogenase gene (gnd) identified serotype Enteritidis (1, 9, 12:g, m:-) as a close relative of the non-motile salmonellae. In most strains of biotype Gallinarum, the fliC gene is complete, intact and identical in sequence to that of Enteritidis, but isolates of three ETs had a stop codon at position 495. The fliC sequences of the ETs of Pullorum differed from that of Enteritidis in having non-synonymous changes in either two or three codons and a synonymous change in one codon. The sharing of distinctive alleles at three metabolic enzyme loci and a stop codon in flgK indicates that the non-motile salmonellae are monophyletic and that their most recent common ancestor was non-motile. Since diverging from that ancestor, the Pullorum lineage has evolved more rapidly than the Gallinarum and Ga/Pu 1 lineages.
The use of magnetic resonance imaging (MRI) provides visual evidence of cerebral deposits of paramagnetic metals. The usefulness of MRI is described in connection with the manganese poisoning of a 44 year old arc welder who had been engaged in the repair and recycling of railroad track made of manganese steel alloy.
The changes in blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), parathyroid hormone (PTH), arginine vasopressin (AVP) and the cyclic nucleotides cAMP and cGMP were measured during a fluctuating BV cycle in 15 patients with end-stage renal failure maintained on chronic hemodialysis (HD). HD consisted of 4 periods of about 60 min each. The first half of each HD period consisted of ultrafiltration (UF) greater than 1,000 ml/h, and the second half consisted of no UF. Changes in relative BV were measured using continuous hemoglobinometry. Total BV at the end of treatment was 74.3 +/- 6.9% of the pretreatment volume. A significant positive correlation between BV and the levels of ANP, PTH, Epi and cGMP and an inverse correlation between BV and PRA, Aldo, AVP and NE were demonstrated. While mean values of NE and AVP levels were directly related to actual changes in BV, individual values did not homogeneously reflect this relationship. The cyclic nucleotides cGMP and cAMP did not follow immediate BV changes, but showed a significant decrease correlated with diminished BV. Based on a pre-postdialysis analysis, significant changes in PRA and Aldo were missing. It seems possible that vascular stability in dialysis patients may be maintained by the response of NE and AVP, and not by the renin-aldosterone system. The changes in ANP and cGMP values correlated most significantly (r = 0.38 and r = 0.51, p < 0.005) with the changes in BV, but no single variable could explain the blood pressure regulation during HD with intermittent rapid UF.
Hypotension is a frequent complication in patients subjected to regular hemodialysis. Insufficient regulation of blood pressure following dialysis with ultrafiltration has been attributed to a lack in hormone activation. To determine whether altered production of vasoactive hormones is involved in the breakdown of blood pressure regulation during hemodialysis (HD), blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), intact immunoreactive parathyroid hormone (iPTH) and arginine vasopressin (AVP) were examined. The relative BV was measured by continuous hemoglobinometry during the HD period of about 240 min. The total decrease in BV at the end of treatment was 23.5 +/- 4.8% of the pretreatment value. Systolic blood pressure (SBP) was 99.6 +/- 23.0 mmHg before dialysis compared with 74.6 +/- 18.8 mmHg at the end of dialysis and heart rate (HR) increased from 76.3 +/- 5.5/min before to 92.0 +/- 10.0/min at the end of dialysis. Despite the wide range of interindividual variance, the hormonal changes indicate that hypotensive patients under HD develop reduced sensitivity of the angiotensin-renin, adrenergic and AVP systems to volumetric stimuli. A paradoxical activation in iPTH and PRA independent Aldo secretions is apparent.
The health effects of chronic human T-cell lymphotropic virus type I (HTLV-I) infection were examined in a cohort of Japanese men who had emigrated from Okinawa, Japan, and had been participants in a prospective study in Hawaii since 1965. In the present follow-up study carried out in 1987-1988, various health indicators were measured in the subjects, whose mean age was 72.5 years. Participation rates were lower in the HTLV-I seropositives than in the seronegatives (46.7% vs. 76.0%) in the > or = 75-year age group. Lack of participation was significantly correlated with a high HTLV-I antibody titer. Among the participants, seropositive subjects were significantly more likely than the seronegatives to have lymphocytopenia (32.7% vs. 17.7%) and mild anemia (25.5% vs. 14.1%) after adjustment for age and socioeconomic status. The seropositives also had a higher frequency of acupuncture therapy (age-adjusted odds ratios were 2.1 and 4.2 for 1-5 treatments and > or = 6 treatments, respectively). Proportions of subjects who had been hospitalized at least twice were higher among the seropositives in the oldest age groups, 70-74 years and > or = 75 years, but not in those aged 65-69 years. Although specific disease conditions were not identified in this study, hematologic data, treatment histories, and the correlation between participation status and HTLV-I antibody titers suggest that chronic HTLV-I infection may be associated with as yet undefined adverse health effects, particularly in older age groups.
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The growth of a large proportion of estrogen receptor-positive breast tumors is stimulated by estrogen and can often be controlled through antiestrogen therapy. Resistance to antiestrogen (AE) therapy can occur while tumors retain the expression of estrogen receptors (ERc) and remain functionally responsive to estrogens. The ability of specific antiestrogen binding sites (AEBS) to prevent AE from interacting with ERc has been examined as a possible mechanism through which this appropriation of AE could interfere with antiestrogen action. Comparisons were performed between uterine preparations where ERc activity exceeded AEBS binding and liver preparations where AEBS binding predominated. Identical estimates of ERc activity were obtained in uterine preparations using either [3H]estradiol or [3H]-4OH-tamoxifen and radioinert diethylstilbestrol (alpha,alpha'-diethyl-4,4'-stilbenediol) to estimate nonspecific binding. AEBS binding was observed only when [3H]-4OH-tamoxifen was used, while binding to Type II sites was resolved only with [3H]estradiol. When excess AEBS activity predominated, analyses with radiolabeled estrogen and antiestrogen present simultaneously showed that virtually all of the antagonist was bound to AEBS with little of the antagonist available to associate with ERc. In an effort to relate these observations to AE resistance per se, ERc and AEBS were measured in MCF-7 human breast cancer cells (ERc-positive, responsive to estrogens and antiestrogens) and in variant AE-insensitive LY-2 human breast cancer cells (ERc-positive, responsive only to estrogens). In AE-resistant LY-2 cells, the ratio of AEBS:ERc was approximately three times greater than in MCF-7 cells. Examination of 128 human breast carcinomas revealed that AEBS activity was present and could exceed ERc activity. Importantly, the partition of significant AE away from ERc was observed in human specimens. These observations identify a biochemical mechanism for antiestrogen resistance through which AE access to ERc can be totally incapacitated while sensitivity to estrogens continues. These observations indicate that AEBS activity, in addition to ERc activity, may provide helpful information for predicting the response of certain cancers to hormonal therapy.
The sequence of the Leishmania tarentolae SSU rRNA (small subunit or 18S rRNA) gene was completely determined from 2 different strains and used to determine phylogenetic relationships between this organism and other trypanosomatids. Extensive structural similarities were observed between L. tarentolae and mammalian leishmanias the SSU rRNA. Phylogenetic reconstructions, using distance matrix or parsimony methods, showed large evolutionary distances between trypanosomes, either African and American, and L. tarentolae. Further analysis using intergenic rDNA spacer (IGS) sequences as probes in dot blot experiments confirmed the results obtained with the SSU rDNA comparisons. The data presented here clearly indicate that L. tarentolae is closely related to the mammalian parasite Leishmania donovani and highly divergent from trypanosomes.
It has recently been demonstrated that the bacteriophage-borne gene (speC) encoding pyrogenic exotoxin C is harbored by phylogenetic lineages representing virtually the entire breadth of genomic differentiation present in the species Streptococcus pyogenes (J. M. Musser, A. R. Hauser, M. H. Kim, P. M. Schlievert, K. Nelson, and R. K. Selander, Proc. Natl. Acad. Sci. USA 88:2668-2672, 1991). To determine whether the speC genes occurring in association with divergent chromosomal genotypes (clones) are identical or represent a group of allelic variants, we sequenced speC from 23 S. pyogenes strains representing 15 clones identified by multilocus enzyme electrophoresis. Two alleles of speC are present in natural populations, and each allele occurs in clones that are well differentiated in overall chromosomal character; in one case, isolates of a single clone had different speC alleles. We interpret these patterns of toxin allele-clone distribution as evidence of occasional episodes of speC horizontal dissemination, presumably by bacteriophage-mediated gene transfer and recombination.