Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel.
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Arabs↗
Biomedical subjects
D A Scott
Publications and source records attributed to D A Scott.
Infections in cancer patients: some controversial issues.
Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged (more than 2 weeks) or profound (below 100 granulocytes/microliters) granulocytopenia. Agents chosen should suppress aerobic but not anaerobic flora (maintain colonization resistance) and need to have an effect on both the oral cavity and esophagus as well as the intestines.
Anti-Bacterial Agents↗
Family-centred practice in the interface between child welfare and the alcohol and drug field.
Recently publicized cases of child abuse and neglect ahve highlighted the complexity of interaction between professionals in the alcohol and drug field and those in the child welfare field. Despite exhortations to practitioners in both fields to see their clients from a "family-centred perspective", a range of psychological, ethical, conceptual, professional and organizational factors mean that this often remains an elusive goal. In this paper the obstacles to adopting a family-centred approach which cuts across different professions and fields of service are identified. These factors interact in complex ways and although workers feel the tensions, it is difficult for them to perceive the set of constraints as a whole from the vantage point of an actor in the process. By identifying and analysing these obstacles workers in both fields may be better able to collaborate in maximizing the opportunities which also exist for family-centred practice.
Journal Article↗
Cloning and sequencing of the genes encoding Escherichia coli cytolethal distending toxin.
Escherichia coli strains expressing cytolethal distending toxin (CDT) cause elongation of CHO cells at 24 h, followed by progressive cellular distention and death for up to 120 h. Similar distention and cytotoxicity are seen in HeLa, HEp-2, and, to a lesser extent, Vero cells. The initial elongation in CHO cells is indistinguishable from that caused by E. coli heat-labile toxin (LT). In contrast to those from LT strains, supernatants from these strains have no effect on Y-1 adrenal cells. TnphoA was introduced into CDT-positive E. coli E6468/62 (O86:H34), isolated from a child with diarrhea, and 13 CDT-negative transconjugants were identified. DNA probes constructed from DNA flanking the TnphoA insertion sites of CDT-negative mutants were used to identify a CDT-positive clone from an E6468/62 genomic library with a 5.5-kb insert. Exonuclease deletions were created and assayed in CHO cells. In this manner, a 2.3-kb CDT-active region was defined, and the nucleotide sequence was determined. Sequence analysis identified three open reading frames (ORFs), designated cdtA, cdtB, and cdtC. These contain 711, 819, and 570 bp, respectively, and encode polypeptides with predicted molecular masses of 25.5, 29.8, and 20.3 kDa, respectively. Each ORF has a putative signal sequence, and there are 4-bp overlaps between cdtA and cdtB and between cdtB and cdtC. The nucleotide and predicted amino acid sequences have no significant homology with those of any previously reported genes or proteins. By in vitro transcription-translation and an anti-alkaline phosphatase immunoblot, native proteins and/or fusion proteins corresponding to each ORF were identified.
Amino Acid Sequence↗
Ratiometric methodology for NAD(P)H measurement in the perfused rat heart using surface fluorescence.
The surface fluorescence of the isolated perfused rat heart has been evaluated for the purpose of NAD(P)H quantitation. With the use of excitation at 340, 380, 415, and 430 nm with emission detection at 500 +/- 20 nm, the intensities at 340 and 380 nm excitation were found to be linearly related during NAD(P)H oxidation/reduction induced by changes in substrate availability. Changes in cardiac NAD(P)H caused similar changes at 340 and 380 nm excitation, but those at 340 nm were of greater magnitude. Isolated cardiac mitochondria exhibited essentially identical optical properties during changes in NAD(P)H content induced by changes in substrate availability and by NAD(H) oxidation/reduction caused by coupled phosphorylation of ADP. The changes in redox status of both isolated mitochondria and the intact perfused heart can be expressed by a 340/380 excitation fluorescence ratio because of these relationships. This value assumed a minimum and maximum value under conditions of complete oxidation and reduction, respectively. Use of this ratio in the perfused heart avoids the artifacts caused by cardiac motion and tissue stretch. Removal of motion artifacts with an excitation ratio could only be accomplished if the measurements at 340 and 380 nm were estimated at the same point in the cardiac cycle. A method of cardiac waveform reconstruction and signal averaging is described to obtain these data from sequential measurements. With these techniques, the reduction of cardiac NAD(P)H can be expressed as a percentage of the range obtained between minimum and maximum reduction. The described technique is of general utility in the assessment of cardiac bioenergetics.
Animals↗
Quantitation of myoglobin saturation in the perfused heart using myoglobin as an optical inner filter.
Quantitation of metabolic parameters using the technique of cardiac surface fluorescence is complicated by motion and changes in tissue absorption. Because ratio fluorescence methodology can be applied to eliminate motion-induced errors, in the current study, we used a ratio fluorescence technique to evaluate myoglobin saturation in the perfused rat heart, since myoglobin is the major oxygen-dependent light absorbing species in this tissue. Changes in myoglobin saturation can affect surface fluorescence measurements as a result of the inner filter effect. Optical scans of heart extracts indicated the major absorption peak is due to myoglobin and its peak wavelength shifts from 415 to 430 nm upon deoxygenation. To monitor this shift in hearts, the isolated perfused heart was loaded covalently with the fluorescent dye 7-diethylaminocoumarin-3-carboxylic acid by brief perfusion with the succinimidyl ester. This dye has an excitation maximum in the region of maximal absorption by myoglobin and allows for monitoring myoglobin oxygenation using the inner filter effect. The dye localized to endothelial cells and increased the surface fluorescence in this wavelength region approximately 50-fold above background levels without affecting cardiac function. An equation was derived to estimate the fraction of myoglobin in the oxygenated state from changes in the fluorescence 415/430 excitation ratio. From this fraction, the average PO2 in the environment of myoglobin was estimated under several perfusion conditions. We report that retrograde perfusion in the Langendorff mode at either 60 or 120 mmHg pressure resulted in full oxygenation of myoglobin with use of cell-free perfusate equilibrated with 95% O2.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Computer systems for dental practice management: a new generation of independent dental software.
A new generation of computer programs for dental patient management eliminates total dependence on the vendor for programming support. The software design enables information collected with the dental system to be transferred to popular off-the-shelf programs designed for business. A simplified example is used to illustrate the practitioners the advantages of this type of data structure management. Programs designed on this basis offer optimum performance and expandability for both present and future needs.
Computer Systems↗
Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen.
Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle-bone disease. Dermal fibroblasts from most affected individuals produce about half the usual amount of type I procollagen, as a result of a COL1A1 "null" allele. Using PCR amplification of genomic DNA from affected individuals, followed by denaturing gradient gel electrophoresis (DGGE) and SSCP, we identified seven different COL1A1 gene mutations in eight unrelated families with OI type I. Three families have single nucleotide substitutions that alter 5' donor splice sites; two of these unrelated families have the same mutation. One family has a point mutation, in an exon, that creates a premature termination codon, and four have small deletions or insertions, within exons, that create translational frameshifts and new termination codons downstream of the mutation sites. Each mutation leads to both marked reduction in steady-state levels of mRNA from the mutant allele and a quantitative decrease in type I procollagen production. Our data demonstrate that different molecular mechanisms that have the same effect on type I collagen production result in the same clinical phenotype.
Alleles↗
Diarrheal disease aboard a U.S. Navy ship after a brief port visit to a high risk area.
In August 1988, a study was conducted to determine the etiology and risk factors associated with travelers' diarrhea among U.S. military personnel after a 5-day port visit to Alexandria, Egypt. Twenty-one percent of the 2,747 evaluated crew members of the USS John F. Kennedy reported an episode of acute diarrhea, which led to 155 sick-call visits and at least 110 lost man-days. The most common pathogen identified was enterotoxigenic Escherichia coli, and all isolated bacterial enteropathogens were sensitive to quinolone drugs. Independent risk factors for the development of diarrhea included: (1) consuming any meal ashore and specifically eating meats, desserts, or a buffet meal; and (2) a recent history of travelers' diarrhea. These data indicate that even brief port visits to developing countries pose a major threat to the health of U.S. shipboard personnel.
Acute Disease↗
Treatment of gastrointestinal infections.
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AIDS-Related Opportunistic Infections↗
Neurologic changes during carotid endarterectomy under cervical block predict a high risk of postoperative stroke.
BACKGROUND: This study was undertaken to confirm a previous report that patients having neurologic changes with carotid artery clamping were at greater risk of developing permanent postoperative neurologic complications after carotid endarterectomy. METHODS: Superficial and deep cervical plexus blocks were performed in 389 patients undergoing carotid endarterectomy. The patients were premedicated and sedated to a level that allowed awake neurologic assessment. Intraoperative neurologic changes were recorded and all patients were examined postoperatively by an independent anesthesiologist to record postoperative neurologic outcome. RESULTS: Trial carotid artery cross clamping resulted in 24% of patients having neurologic changes that usually responded to declamping and shunt insertion. Postoperative permanent neurologic complications occurred in 2.6% of patients, but were more common in patients who had neurologic changes associated with carotid artery cross clamping (6.6% compared to 1.1%, P < 0.01). Thrombosis of the carotid artery was the most common finding in patients who underwent reexploration of the carotid artery after developing postoperative neurologic changes. CONCLUSIONS: This study confirms that patients undergoing carotid endarterectomy under cervical plexus block who have intraoperative neurologic changes have a sixfold increase in the chance of developing a postoperative stroke. This high-risk group may benefit from antithrombotic therapies to improve their outcome.
Aged↗
Regulation of cardiac mitochondrial calcium by average extramitochondrial calcium.
A system to perifuse isolated rat heart mitochondria was designed to study the relationship between mitochondrial matrix free Ca2+ and extramitochondrial free Ca2+ under conditions in which the latter concentration could oscillate over a range typical of that expected in vivo. We tested the hypothesis that the level of intramitochondrial Ca2+ responds to the average extramitochondrial Ca2+ in the heart. Mitochondria were immobilized within an optical chamber for measurement of endogenous NAD(P)H and fura 2 fluorescence. NAD(P)H increased significantly on provision of substrates and decreased reversibly in the presence of ADP, indicating maintenance intact coupled respiration by this preparation. Matrix free Ca2+ was measured using fura 2-loaded mitochondria and, in parallel experiments, media free Ca2+ was measured with fura 2 in the absence of mitochondria. Oscillation of extramitochondrial Ca2+ from < 0.1 microM to approximately 2 microM at frequencies of 0.5, 1.0, and 1.25 cycles/s produced steady-state levels of matrix Ca2+ that were independent of frequency but proportional to the average media free Ca2+ concentration. Matrix Ca2+ increased to a steady state on an increase in the extramitochondrial average Ca2+ concentration with a half-time (t1/2) of approximately 2 min at 22 degrees C. Oscillation of mitochondrial Ca2+ was not observed under any conditions tested. The data are taken to indicate that in vivo, the concentration of mitochondrial matrix free Ca2+ is a steady state that is proportional to the average extramitochondrial Ca2+ concentration and that changes in the latter represent a mechanism of signal transduction from the cytosol to the mitochondrial matrix.
Animals↗
Epidural catheter insertion: the effect of saline prior to threading in non-obstetric patients.
The effects of injecting normal saline 4 ml through the epidural needle before catheter passage on ease of catheterisation and incidence of certain complications were investigated in 189 non-obstetric patients. The use of saline had no effect on ease of catheterisation, with 84.2% of Group S patients (saline, n = 95) and 88.3% of Group C patients (control, n = 94) having the difficulty of passing the catheter rated as "easy" (P = 0.31). The incidence of complications was not affected by the use of saline. Paraesthesia occurred in 27.4% of Group S patients compared with 16.0% of Group C patients (P = 0.08). Epidural venous cannulation occurred in 6.3% of Group S patients versus 11.7% of Group C patients (P = 0.30). We conclude that the use of 5 ml of normal saline prior to catheter threading provides no significant benefit in improving the ease of catheterisation or decreasing the incidence of catheter complications.
Catheterization↗
Neurological damage resulting from extracorporeal shock wave lithotripsy when air is used to locate the epidural space.
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Adult↗
A computer program to aid in calculating similarity indexes from DNA fingerprints.
DNA SIMDEX is a DOS-based computer program designed to assist in the visual scoring of DNA fingerprint assays. DNA SIMDEX uses the migration distances of the individual DNA bands to generate lists of probable matching and nonmatching bands and automatically calculates a probable similarity index between DNA fingerprints based on these initial predictions. After comparisons are edited by the user, the final similarity index, along with accompanying data, can be saved on a floppy disk or hard drive for easy storage and retrieval or can be printed directly on a laser or line printer. The program has been developed to function with or without an image-analysis system, thus making it an inexpensive alternative for small laboratories.
DNA Fingerprinting↗
Identification by high-performance liquid chromatography of tyrosine ammonia-lyase activity in purified fractions of Phaseolus vulgaris phenylalanine ammonia-lyase.
Activities of phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) were assessed at each stage of a three-step purification of PAL. Assays were performed by high-performance liquid chromatographic (HPLC) separation and ultraviolet detection of reaction products. Use of HPLC permitted assay of low activities of PAL and TAL for periods up to approximately four and two days, respectively. HPLC also facilitated the accurate quantitation of the product of the TAL reaction, trans-p-coumaric acid, which was observed to isomerize readily under experimental conditions. PAL and TAL were associated throughout the purification procedure, with TAL activity at 0.6-1.3% of PAL activity. It was concluded that, contrary to previous reports, TAL and PAL activities are mediated by the same enzyme, or else by chromatographically very similar enzymes.
Ammonia-Lyases↗
Prevention of tachycardia with atenolol pretreatment for carotid endarterectomy under cervical plexus blockade.
A double-blind, randomised, controlled trial of forty patients was carried out to determine if oral atenolol pretreatment would reduce the incidence of tachycardia during carotid endarterectomy performed under cervical plexus block. Twenty patients received a placebo and twenty patients 50 mg of atenolol two hours prior to surgery. The superficial and deep cervical blocks were performed with 1.5% lignocaine containing 1:200,000 adrenaline. The patients were monitored with the V5 lead of the electrocardiogram and intra-arterial blood pressure. These measurements were recorded on a correctly calibrated paper recorder. Tachycardia (heart rate greater than 90 beats per minute for more than three minutes) occurred in thirteen patients in the placebo group and two patients in the atenolol group (P less than 0.01). There was no difference in the occurrence of bradycardia, hypotension or hypertension between the two groups. It is concluded that atenolol pretreatment is an effective method of reducing the incidence of tachycardia during carotid endarterectomy performed under cervical plexus blockade.
Aged↗
The epidemiology of hepatitis C virus antibody in Yemen.
A cross-sectional survey of 348 subjects without evidence of liver disease was conducted to investigate the prevalence and risk factors for hepatitis C virus antibody (anti-HCV) seropositivity in the Yemen Arab Republic. The mean age of study subjects was 28.7 years (range 3-80), and 61% were males. Using commercial enzyme-linked immunosorbent assays (ELISA), 6.0% (95% confidence interval [CI] 3.8-9.1) of subjects were anti-HCV-positive, 13.5% were hepatitis B surface antigen-positive (HBsAg-positive), and 51.4% were positive for at least one serologic marker of prior hepatitis B infection. Nine (2.6%; 95% CI 1.2-4.9) of the 21 ELISA-positive sera were confirmed to be anti-HCV positive by a recombinant immunoblot assay. Anti-HCV seropositivity was significantly associated with age (odds ratio [OR] 2.0 for each 10-year increase in age) and prior surgery (OR 10.1), but was not associated with a history of prior blood transfusion or markers of hepatitis B infection. These preliminary data suggest that hepatitis C may pose a substantial health threat in Yemen.
Adolescent↗