At the cutting edge of care....
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History, 19th Century↗
Biomedical subjects
W Miller
Publications and source records attributed to W Miller.
Rhodotorula Rubra peritonitis in an HIV+ patient on CAPD.
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Adult↗
[Quality assurance in goiter surgery by rate of recurrent nerve paralysis].
We analyzed the results of 1147 thyroid operations performed at a teaching hospital over a period of 3 years. These results were submitted to an internal quality control. We studied the factors that influenced the surgical complication rate and particularly the rate of a palsy of the recurrent laryngeal nerve. Operations of 'simple' goitres showed only a very low risk of post-operative complications whereas the risk for patients with Graves' disease, a carcinoma or a recurrent goitre was a markedly higher. The rate of a permanent palsy of the recurrent laryngeal nerve was just 0.5% for a simple goitre but as high as 7.8% for a relapse. Not just the underlying disease but the surgeon and his surgical technique play an important role in the incidence of a palsy of the recurrent laryngeal nerve. If a sophisticated surgical technique is applied without exposing the recurrent laryngeal nerve but leaving the fascial layer that covers the nerve and the vessels of the throat intact, there are no differences between the results of these operations and such where the nerve is routinely demonstrated. The follow-up of the patients with recurrent nerve palsy showed a medium recovery time of half a year. In one of six patients with temporary palsy the restitution was seen after more then one year.
Adolescent↗
Globin gene server: a prototype E-mail database server featuring extensive multiple alignments and data compilation for electronic genetic analysis.
The sequence of virtually the entire cluster of beta-like globin genes has been determined from several mammals, and many regulatory regions have been analyzed by mutagenesis, functional assays, and nuclear protein binding studies. This very large amount of sequence and functional data needs to be compiled in a readily accessible and usable manner to optimize data analysis, hypothesis testing, and model building. We report a Globin Gene Server that will provide this service in a constantly updated manner when fully implemented. The Server has two principal functions. The first (currently available) provides an annotated multiple alignment of the DNA sequences throughout the gene cluster from representatives of all species analyzed. The second compiles data on functional and protein binding assays throughout the gene cluster. A prototype of this compilation using the aligned 5' flanking region of beta-globin genes from five species shows examples of (1) well-conserved regions that have demonstrated functions, including cases in which the functional data are in apparent conflict, (2) proposed functional regions that are not well conserved, and (3) conserved regions with no currently assigned function. Such an electronic genetic analysis leads to many readily testable hypotheses that were not immediately apparent without the multiple alignment and compilation. The Server is accessible via E-mail on computer networks, and printed results can be obtained by request to the authors. This prototype will be a helpful guide for developing similar tools for many genomic loci.
Animals↗
Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.
We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.
Adolescent↗
Cadmium toxicity to rainbow trout Oncorhynchus mykiss Walbaum and brown trout Salmo trutta L. over extended exposure periods.
The toxicity of cadmium in water is well known, but there have been few reports on the long-term effects of this metal on fish at concentrations near the European inland water standard of 5 micrograms Cd liter-1. This paper describes experiments in which adult rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta were exposed to cadmium concentrations near water quality standard levels for periods of up to 90 weeks. The survival and growth of these fish were assessed, and sperm and eggs were stripped from them to conduct early-life-stage tests. Continuous exposure of rainbow trout adults to cadmium concentrations of up to 5.5 micrograms Cd liter-1 did not affect their survival or growth. However, eggs obtained from rainbow trout exposed to 1.8 and 3.4 micrograms Cd liter-1 failed to develop to the fry stage. Oogenesis appeared to be delayed in brown trout exposed to 9.3 and 29.1 micrograms Cd liter-1, but the eggs and fry that were produced developed normally after fertilization. Adult brown trout suffered considerable mortality in the 29.1 micrograms Cd liter-1 treatment, with a median period of survival of 54 weeks.
Animals↗
Chaining multiple-alignment blocks.
We derive a time-efficient method for building a multiple alignment consisting of a highest-scoring chain of "blocks," i.e., short gap-free alignments. Besides executing faster than a general-purpose multiple-alignment program, the method may be particularly appropriate when discovery of blocks meeting a certain criterion is the main reason for aligning the sequences. Utility of the method is illustrated by locating a chain of "phylogenetic footprints" (specifically, exact matches of length 6 or more) in the 5'-flanking regions of six mammalian epsilon-globin genes.
Algorithms↗
Recent developments in linear-space alignment methods: a survey.
A dynamic-programming strategy for sequence alignment first proposed in 1975 by Dan Hirschberg can be adapted to yield a number of extremely space-efficient algorithms. Specifically, these algorithms align two sequences using only "linear space," i.e., an amount of computer memory that is proportional to the sum of the lengths of the two sequences being aligned. This paper begins by reviewing the basic idea, as it applies to the global (i.e., end-to-end) alignment of two DNA or protein sequences. Three of our recent extensions of the technique are then outlined. The first extension computes an optimal alignment subject to the constraint that each position, i, of the first sequence must be aligned somewhere between positions L[i] and U[i] of the second sequence, for given values of L and U. The second finds all aligned position pairs (i.e., potential columns of the alignment) that occur in an alignment whose score exceeds a given threshold. The third treats the case where each of the two sequences is allowed to be an alignment (e.g., a sequence of aligned pairs), using a sensitive scoring scheme. We also describe two linear-space methods for computing k best local (i.e., involving only a part of each sequence) alignments, where k > or = 1. One is a linear-space version of the algorithm of Waterman and Eggert (1987), and the other is based on the strategy proposed by Wilbur and Lipman (1983). Finally, we describe programs that implement various combinations of these techniques to provide a multisequence alignment method that is especially suited to handling a few very long sequences. The utility of these programs is illustrated by analysis of the locus control region of the beta-like globin gene cluster of several mammals.
Algorithms↗
Constructing aligned sequence blocks.
This paper presents an efficient method for constructing aligned blocks (i.e., gap-free multiple alignments) from a set of pairwise alignments. The method is more sensitive than some earlier block-constructing methods for detecting conserved sequence regions. The technique is applied to analyze conserved regions in protein prenyltransferases and to detect regulatory elements in the 5' flank of the beta-globin gene.
Algorithms↗
A note about computing all local alignments.
A recent paper in this journal by G. Barton proposed an efficient algorithm for locating locally optimal alignments between two sequences. Although the paper claims that all such alignments are found, the approach frequently fails to detect some of the significant matches. This note explains the deficiency.
Algorithms↗
Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens.
A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.
Adult↗
Delayed toxic shock syndrome in sinus surgery.
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Chronic Disease↗
Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications.
The cellular immunoincompetence which follows bone marrow transplantation (BMT) allows both primary and reactivation infection with herpes viruses. We report the overall incidence and timing of varicella zoster virus (VZV) infections after BMT, including the clinical course, complications and associated clinical risk features. Of 1186 patients undergoing BMT through 1989, 216 patients developed VZV infection between 4 days and 10.8 years after BMT; 86% of them within the first 18 months. Of all patients transplanted, 15 +/- 3% by 6 months and 52 +/- 14% by 5 years had developed VZV infection. Dermatomal zoster represented 62% of the infections, while 32% had complicated VZV infection--CNS, disseminated or visceral zoster. All serious infections occurred within 7 months of BMT but only two patients died, both from VZV pneumonitis. Allogeneic and autologous recipients had a similar incidence of VZV infection. VZV seropositive patients had more frequent, earlier and often more complicated or disseminated infections. Age > or = 10 years and radiation in the pre-transplant conditioning were significantly and independently associated with higher rates of VZV infection within a multivariate regression model. Using this model, we could define clinical risk groups with distinctly different hazards of VZV infection: age > 10 years, radiation pre-BMT and VZV seropositive patients had a 44% incidence by 3 years versus age < 10 years, no radiation and VZV seronegative had a 0% incidence by 3 years. Acyclovir assigned for prophylaxis of CMV or HSV infection had no effect on the timing or incidence of VZV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Acyclovir↗
Comparative analysis of the locus control region of the rabbit beta-like gene cluster: HS3 increases transient expression of an embryonic epsilon-globin gene.
The rabbit homolog to the locus control region (LCR) of the human beta-like globin gene cluster was isolated, and long segments containing the DNase I hypersensitive sites (HS) were sequenced. The order and spacing of HS4, HS3, HS2 and HS1 are conserved between rabbit and human. Alignment of these sequences with their homologs from human, goat, and mouse shows that very long segments of DNA match between species, for over a thousand base pairs on either side of the previously identified functional cores, indicating that some important functions are found outside the cores. The activity of rabbit HS2 and HS3 was tested by attaching each to a novel reporter gene constructed by inserting the luciferase coding region into the rabbit epsilon-globin gene. In contrast to previous reports showing no effect of human or mouse HS3 on transient expression, both the rabbit HS2 and HS3 DNA fragments separately increased transient expression from the epsilon-luciferase hybrid gene and expression from stably integrated constructs in K562 erythroleukemia cells.
Animals↗
Pregnancy associated plasma protein A as a marker for Down syndrome in the second trimester of pregnancy.
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Down Syndrome↗
Constrained sequence alignment.
This paper presents a dynamic programming algorithm for aligning two sequences when the alignment is constrained to lie between two arbitrary boundary lines in the dynamic programming matrix. For affine gap penalties, the algorithm requires only O(F) computations time and O(M+N) space, when F is the area of the feasible region and M and N are the sequence lengths. The result extends to concave gap penalities, with somewhat increased time and space bounds.
Algorithms↗
Maternal serum screening for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 11 and 15 weeks of pregnancy to detect fetal chromosome abnormalities.
OBJECTIVE: The purpose of this prospective study was to assess the value of maternal serum screening between 11 and 15 weeks of gestation to detect fetal Down syndrome. STUDY DESIGN: Blood samples were collected on 993 women between 11 and 15 weeks' gestation before amniocentesis. Ninety percent were > or = 35 years old. Samples were coded and assayed for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Medians were established at each week between 11 and 15 from 836 normal, singleton pregnancies. RESULTS: We used a computer-generated cut-off risk for Down syndrome of one in 365 at term; nine of 11 (82%) Down syndrome pregnancies were identified. There were 23% false-positive results in women > or = 35 years old and 6% in those < 35 years. CONCLUSION: These results suggest that maternal serum screening between 11 and 15 weeks may provide an acceptable alternative to screening between 16 and 20 weeks.
Chorionic Gonadotropin↗
Single and booster dose responses to an inactivated hepatitis A virus vaccine: comparison with immune serum globulin prophylaxis.
Pre- and postexposure prophylaxis against hepatitis A virus (HAV) infection with immune serum globulin (Ig) is only effective for 4-6 months. We compared the safety, tolerability and immunogenicity of a single i.m. injection of Ig with a single and booster dose of an inactivated hepatitis A virus vaccine (iHAV) in adults. Healthy volunteers (18-50 years) received a single Ig i.m. injection (n = 30), or iHAV i.m. (n = 15) at 0 and 24 weeks, or placebo (n = 4) at the same intervals. Anti-HAV seroconversion was measured by radioimmunoassay (RIA) and neutralizing antibodies by an antigen reduction assay. After Ig injection (0.06 ml/kg), anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12 and 0% by week 20. In contrast, after a single 25 ng dose, RIA seropositivity in iHAV vaccinees was 80% by week 2, reaching 100% by week 5 and persisted up to week 24, at which time anti-HAV geometric mean titres (GMT) were two fold higher than those seen at week 1 after Ig. Postbooster anti-HAV titres in iHAV recipients rose within 4 weeks to 73-fold greater than the peak GMT seen one week after Ig, and 400-fold higher than GMT at 12 weeks after Ig. Neutralizing antibody titres after iHAV followed a similar pattern, as observed for anti-HAV. iHAV was well tolerated; placebo and vaccine tolerability were indistinguishable, with no serious adverse experiences observed. In conclusion, active vaccination with a single iHAV dose may eventually replace Ig for pre-exposure prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗