Nine families with the SCA3/Machado-Joseph disease type of inherited ataxia.
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Adult↗
Biomedical subjects
D Moore
Publications and source records attributed to D Moore.
Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.
We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.
Acetates↗
Jealousy induction as a predictor of power and the use of other control methods in heterosexual relationships.
26 male and 87 female college students filled out Stets' Psychological Aggression Scale, Stets' Interpersonal Control Scale, Straus' Physical Violence Scale, and Fisch and Brainerd's Use and Approval of Jealousy-inducing Behaviors Scale. Use and approval of jealousy-inducing behaviors were good predictors of high need for interpersonal control and the use of psychological aggression. The use of jealousy-inducing behaviors but not the approval of these behaviors was a strong predictor of physical aggression in romantic relationships.
Adult↗
Cholesterol levels among Japanese Americans and other populations: Seattle Nikkei Health Study.
The purpose of this study was to compare average cholesterol levels between Seattle based Japanese Americans and three other populations: U.S. population, native Japanese population and native Japanese urban workers. A total of 1,466 Japanese Americans (724 men and 742 women) participated in cardiovascular disease screening in the Seattle area during 1989 94. Data sources for comparisons are from the Third National Health and Nutrition Examination Survey for 1988-91, the results of the National Cardiovascular Disease Examination Survey in Japan for 1990, and cardiovascular disease screening conducted by the Epidemiological Arteriosclerosis Research Institute in Japan for 1989. Total cholesterol and triglyceride levels of Seattle Japanese American men and women were highest among the four populations. Among men, high density lipoprotein cholesterol (HDL-C) levels for Seattle Japanese Americans and native Japanese were similar and fell between those of urban Japanese workers and the U.S. population. In women, the average HDL C levels were highest in the Japanese urban workers, second highest in Seattle Japanese Americans, and lowest in both the U.S. population and native Japanese population. These differences in lipid levels may be caused by both genetic and environmental factors, which are now under investigation.
Adult↗
Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice.
Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and practical technique for determining intestinal permeability in clinical pediatric practice.
Adolescent↗
Aneuploid epididymal sperm detected in chromosomally normal and Robertsonian translocation-bearing mice using a new three-chromosome FISH method.
We present a new method to detect epididymal sperm aneuploidy (ESA) in mice using simultaneous fluorescence in situ hybridization (FISH) with DNA probes specific for mouse chromosomes X, Y and 8. The method was applied to Robertsonian (Rb) translocation (8.14) heterozygotes and homozygotes as well as the chromosomally normal B6C3F1. The sex ratios of sperm did not differ from the expected 1:1 and the hybridization efficiencies were approximately 99.7% for over 60 000 sperm analyzed. Mice heterozygous for Rb (8.14) produced about tenfold higher rates of sperm with chromosome 8 hyperhaploidy than did Rb (8.14) homozygotes or chromosomally normal mice, while frequencies of sperm with hyperhaploidies for chromosomes X and Y were unaffected in all three lines of mice. Hyperhaploid frequencies obtained with the ESA method were consistent with those of the previous testicular FISH method and were validated by published data obtained by conventional cytogenetic analyses (meiotic metaphase II and first cleavage). Thus, the mouse three-chromosome ESA assay together with the previously developed aneuploidy assay for human sperm constitute a promising pair of interspecific biomarkers for comparative studies of the genetic and physiologic mechanisms of the induction and persistence of aneuploidy in male germ cells.
Aneuploidy↗
Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cdna-expressed human cytochrome P450.
Midazolam (MDZ) is metabolized in human liver microsomes by the cytochrome P450 (CYP) 3A subfamily to 1'-hydroxy (1'-OH) and 4-hydroxy (4-OH) metabolites. MDZ is metabolized in the rat primarily to 4-OH MDZ, 1'-OH MDZ, and 1',4-dihydroxy (1',4-diOH) MDZ. The kinetics of 4-OH and 1'-OH metabolite formation were determined using hepatic microsomes from control, Ro 23-7637 and dexamethasone-treated male rats. KM values for the major metabolite, 4-OH MDZ, were 24.5, 43.1, and 32.8 microM, and the corresponding Vmax values were 5.9, 28.9, and 13 nmol/mg/min for the control, DEX, and Ro 23-7637-treated animals, respectively KM values for 1'-hydroxylation of MDZ (the major metabolite) after incubation with human liver microsomes from three individuals were 5.57, 2.50, and 3.56 microM, and the corresponding Vmax values were 4.38, 0.49, and 0.19 nmol/mg/min, respectively. In parallel studies using cDNA-expressed human CYP3A4 microsomes, the KM for 1'-OH formation was 1.56 microM, and the corresponding Vmax was 0.16 nmol/mg/min. MDZ was not metabolized by cDNA-expressed human CYP2D6, CYP2E1, or CYP1A2, thus confirming that these isoforms were not responsible for its biotransformation. The formation of 1',4-diOH metabolite in rat and 1'-OH formation in cDNA-expressed human CYP3A4 microsomes showed a decrease in velocity at high substrate concentrations. Inhibition studies showed that MDZ hydroxylation was strongly inhibited by ketoconazole and Ro 23-7637 in rat, human, and cDNA-expressed human CYP3A4 microsomes. alpha-Naphthoflavone stimulated 1'-OH metabolite formation in human and cDNA-expressed human CYP3A4 microsomes at low concentration (10 microM). Naringenin, a flavonoid present in grapefruit juice, also inhibited MDZ metabolism in human liver microsomes. Immunoinhibition studies revealed that polyclonal anti-rat CYP3A2 antibody inhibited MDZ metabolism 80-90% in rat, human, and cDNA-expressed human CYP3A4 microsomes, thus suggesting that members of the CYP3A4 subfamily were involved in the metabolism.
Anesthetics, Intravenous↗
Use of nucleic acid in the diagnosis and management of tuberculosis amplification tests.
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Global Health↗
Pulpal response to dentin etched with 10% phosphoric acid.
PURPOSE: To histopathologically evaluate the effect of etching sound dentin with 10% phosphoric acid, in cavities prepared just within the DEJ on young patients. MATERIALS AND METHODS: Twenty-four orthodontic patients who required premolar extractions were selected for the study. Each of the patients had facial Class V resin composite restorations placed in two maxillary premolars selected for extraction. Each preparation was cut circular, 2 mm in circumference and 0.5 mm into dentin. The dentin of one maxillary premolar preparation, randomly selected, was etched with 10% phosphoric acid (Bisco) for 20 seconds. This was followed by the placement of a dentin bonding agent (All-Bond 2) and a microfilled composite restoration (Silux). The contralateral maxillary premolar, received a similar preparation, but the dentin surface was lined with a light-cured glass ionomer liner before etching of the enamel, followed by placement of a dentin bonding agent and a microfilled resin composite restoration. One of the mandibular premolars was randomly selected as a negative control, having no treatment. Fourteen days after the placement of the restorations, the teeth were extracted, and histologically examined for insult to the pulpal tissues. Injury to the pulp was evaluated by quantitative measures of histopathology, including necrosis, infiltration by inflammatory cells, and other indicators of tissue injury. RESULTS: Using a Kruskal-Wallis analysis, there was no statistically significant difference in pulpal histopathology of the teeth with etched dentin versus teeth with dentin protected by a liner or the negative control teeth (P < 0.05).
Acid Etching, Dental↗
Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute myeloid leukemia.
Leukemia may be viewed as a clonal expansion of blast cells; however, the role of primitive cells and/or stem cells in disease etiology and progression is unclear. We investigated stem cell involvement in leukemia using fluorescence in situ hybridization (FISH), immunofluorescence labeling of hematopoietic subpopulations, and flow cytometric analysis/sorting to discriminate and quantify cytogenetically aberrant stem cells in 12 acute myeloid leukemia (AML) and three myelodysplastic (MDS) specimens. Flow cytometric analysis and sorting were used to discriminate and collect a primitive subpopulation enriched in stem cells expressing CD34+ and lacking CD33 and CD38 (CD34+lin-). A subpopulation containing progenitors and differentiating myeloid cells expressed CD34, CD33, and CD38 (CD34+lin+). Nine specimens contained less than 10% CD34+ cells and, thus, were considered to be CD34- leukemias. Mature lymphoid, myeloid, and erythroid subpopulations were sorted on the basis of antigen-linked immunofluorescence. Cytogenetically aberrant cells in sorted subpopulations were identified using FISH with enumerator probes selected on the basis of diagnosis karyotype. Cytogenetically aberrant CD34+lin- cells were present at frequencies between 9% and 99% in all specimens. CD34+lin- cytogenetically aberrant cells comprised between 0.05% and 11.9% of the marrow/blood specimens. Cytogenetically aberrant CD34+lin+ cells constituted 0.01% tp 56% of the marrow/blood population. These data demonstrate that aberrant cells are present in primitive CD34+ stem cell compartments, even in CD34- leukemias. Stem cell involvement was confirmed further by sorting lymphoid and erythroid subpopulations from eight specimens in which the predominant leukemic population lacked lymphoid/erythroid differentiation markers. In these specimens, as well as in multiple lineages, suggests involvement of a cell(s) with multilineage capabilities. The ability of aberrant CD34+lin- stem cells to contribute to clonal and compartment expansion within immunofluorescently defined subpopulations was evaluated to explore the functional phenotype of aberrant CD34+lin- cells. Analysis of compartment size and aberrant cell frequency suggests that frequency of cytogenetically aberrant stem cells is uncoupled from compartment size. These data suggest that cytogenetically aberrant cells in the primitive compartment show varying abilities to expand primitive compartments. Cytogenetically aberrant CD34+lin- cells precede the blast subpopulation in hierarchical maturation and may in some cases by considered preleukemic, requiring maturation or additional mutations before transformation (eg, compartmental expansion) occurs.
ADP-ribosyl Cyclase↗
Karyotypic heterogeneity and its relation to labeling index in interphase breast tumor cells.
We have used fluorescence in situ hybridization (FISH) with chromosome-specific probes and immunofluorescent detection of in vivo bromodeoxyuridine (BrdUrd) incorporation to evaluate simultaneously numerical chromosome aberrations and proliferative activity of breast cancers. The number of distinct hybridization domains specific for repetitive pericentromeric sequences on chromosomes 1, 7, 11, 15, 17, and X was used as an indicator of copy number of these chromosomes in interphase tumor cells from 23 human breast cancers. Every tumor analyzed showed a heterogeneous distribution of copy number for at least one chromosome type. The copy number distribution for different chromosomes within a tumor frequently showed differing patterns. Major cell populations showing monosomy were relatively rare, occurring only in five cases for chromosome 17, once for chromosome 1, and once for chromosome 15. Flow cytometric analysis of DNA ploidy correlated well with FISH analysis, although flow cytometry failed to detect aneuploidy when only a few chromosomes were affected. To determine whether cell populations with different chromosomal copy numbers have identical proliferation characteristics in vivo, BrdUrd incorporation and centromeric copy number were detected simultaneously. Comparison of the chromosome copy number distribution in BrdUrd-positive cells vs. the distribution of the entire cell population showed different distributions in seven of the 20 cases analyzed. This study demonstrates the common occurrence of chromosome copy number heterogeneity and suggests that a cell phenotype (proliferation) may be associated with genotypic subpopulations.
Adult↗
Use of thiacetazone.
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AIDS-Related Opportunistic Infections↗
Pre-introductory clinical trials of Norplant implants: a comparison of seventeen countries' experience.
This report summarizes the data collected in pre-introductory Norplant implants clinical trials in 17 countries in Latin America, Asia and Africa that were coordinated by either the Population Council or Family Health International (FHI) between 1984 and 1991. A total of 16,282 women between the ages of 18 and 40 years participated in the studies with semi-annual or annual follow-up visits for up to 5 years. Gross cumulative pregnancy rates were < 0.6 per 100 women in the first year and < 1.5 in the second year in all countries. Significant differences in cumulative 5-year pregnancy rates were observed between weight groups 40-49 and 50-59 kg and between 50-59 and 60-69 kg body weight but not between 60-69 kg and those > or = 70 kg. Total cumulative discontinuation rates after five years of Norplant implants use ranged from 35.8 to 60.0 per 100 women. Younger age and low parity were associated with a higher discontinuation rate. Cumulative discontinuation rates for menstrual reasons more than doubled between the end of the first year and second year of use in 13 of 17 countries. This analysis and one previous review provide the only comparison of Norplant contraceptive system study results across a wide diversity of countries; thus allowing an appreciation of the range of clinical experience with Norplant implants and the regional differences in that experience.
Adolescent↗
Autoimmune enteropathy with anti-goblet cell antibodies.
A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.
Autoantibodies↗
Cutaneous T-cell lymphoma in association with silicone breast implants.
BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a chronic malignancy of helper T cells with the CD4 phenotype. It occurs less frequently in young women but is increasing in incidence for unknown reasons. Silicone breast implants have been associated with T-cell-mediated autoimmune reactions. OBJECTIVE: Our purpose was to suggest the hypothesis that CTCL may arise after breast implants and that different patients with CTCL may be stimulated by different antigens. METHODS: Investigators with many patients with CTCL were queried regarding the occurrence of CTCL in women after breast implants. RESULTS: Three cases of confirmed CTCL after breast implants were identified and are reported. In one patient with Sézary syndrome and CTCL, the disease went into remission after removal of implants, resolution of chronic staphylococcal infection, and initiation of photopheresis and interferon alfa therapy. Another patient had progressive disease. CONCLUSION: CTCL may occur in association with breast implants in young female patients, but causality is unknown. If CTCL is antigen driven, then it is likely to result from several different antigens in different groups of patients.
Adult↗
Metastatic melanoma to the pharynx and trachea.
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Adult↗
Modified transnasal endoscopic Lothrop procedure as an alternative to frontal sinus obliteration.
Persistent frontal sinusitis traditionally has been treated with external procedures such as osteoplastic frontal sinus obliteration or the Lynch procedure. Currently, functional endoscopic sinus surgery can be used in most cases to remove disease from the frontal recess, the most frequent site of frontal sinus obstruction, thereby relieving the sinusitis. In some cases, however, frontal recess exploration has failed to relieve the obstruction of the frontal sinus, necessitating an osteoplastic frontal sinus obliteration. We present our experience with a transnasal modification of the Lothrop procedure. The Lothrop procedure, first described in 1914, uses a combined external and transnasal approach to resect the median frontal sinus floor, superior nasal septum, and intersinus septum to drain the frontal sinus. This procedure was largely abandoned and forgotten by modern otolaryngologists. However, with the advent of the computed tomography scan and endoscopic techniques, we sought to reassess the basic tenant of the Lothrop procedure (i.e., wide median frontal sinus drainage). An anatomic study of cadaver heads was performed to quantify the surprisingly large potential opening and to better understand the pertinent anatomy. This procedure was performed on 10 patients, with no resulting complications and no failure to maintain patency of the frontal sinus drainage throughout the follow-up period (mean, 7 months). We are encouraged by our initial favorable results and intend to use the procedure in the future as needs arise.
Adult↗