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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 289 records · Page 16Linked to original sources

The isolation and mapping of EF-Tu mutations in Salmonella typhimurium.

The first isolation of EF-Tu mutations in Salmonella typhimurium is reported. The mutations were isolated by selecting for resistance to the antibiotic mocimycin (= kirromycin). The mocimycin resistant phenotype is the result of mutations in each of two genes, tufA and tufB. Strains mutant in only one of the two tuf genes are sensitive to mocimycin. The spontaneous mutation rate of each of the two tuf genes to a mocimycin resistant phenotype differs by an order of magnitude. tufA maps at minute 71-72, closely linked to rpsL. tufB maps at minute 88-89, closely linked to rpoB. These map positions correspond to the locations of tufA and tufB in E. coli.

Anti-Bacterial Agents↗

Developing a screening index for community studies of somatization disorder.

Despite the low prevalence of somatization disorder in the community, the section of the Diagnostic Interview Schedule used to make the diagnosis--as well as previous diagnostic interviews for the related diagnoses of hysteria, and Briquet's syndrome--is quite lengthy. This study evaluates a somatization disorder screening index derived from completed interviews from the NIMH sponsored Epidemiologic Catchment Area program. A screening index comprised of 11 symptoms of somatization was derived at the Duke ECA site and replicated across the Johns Hopkins, Yale, and Washington University sites. Across ECA sites a screening threshold of five of 11 symptoms correctly identified 41 of 42 respondents with DIS/DSM-III somatization disorder (97.6%) while correctly classifying 14,600 of 14,750 (99.0%) without the disorder. The screening index offers promise as a screening device for clinical and community studies of somatization disorder.

Humans↗

Regional variation in the timing and extent of left ventricular wall motion in normal subjects.

Right anterior oblique cineangiograms from 19 subjects without evidence of heart disease were analysed to assess regional non-uniformity in the time of onset of systolic inward motion, amplitude of systolic motion, time of peak inward motion, and wall motion during the isovolumic relaxation period. The left ventricular silhouette was digitised frame by frame for a full cardiac cycle. These four wall motion variables were quantitatively measured along 40 chords drawn from equally spaced points on the end diastolic silhouette to the nearest point on the end systolic silhouette. Onset of systolic inward motion was significantly non-uniform, being delayed by up to 120 ms in the anterior apical chords compared with the areas of earliest inward motion near the base of the heart. More uniformity was noted in time of peak inward motion; the differences between regions were not statistically significant. Amplitude of systolic motion was significantly less at the apical and mid-anterior segments than elsewhere in the heart. Wall motion during the isovolumic relaxation period is outward and greatest in the mid-anterior segments, but inward in the proximal inferior segments and mitral valve region. These data suggest that contraction of muscle fibres in the anterior apical segments is initially isometric due to the considerable afterload at the onset of contraction, this afterload being the result of earlier contraction elsewhere in the ventricle. This may partly explain the propensity for aneurysms to be located in the anterior apical region. When the timing and extent of wall motion in disease states are analysed, account must be taken of the non-uniformity in the normal heart.

Adult↗

Therapeutic results obtained in vaginal mycoses after single-dose treatment with 500 mg clotrimazole vaginal tablets.

A multicenter, double-blind study of 103 patients with clinically and mycologically documented vulvovaginal candidiasis compared single-dose treatment with a 500 mg clotrimazole vaginal tablet to 3-day treatment with two 100 mg clotrimazole vaginal tablets administered daily. Patients were examined 5 to 10 days (visit 2) and at least 27 days (visit 3) post treatment. At visit 2, mycologic and clinical examinations were negative in 43 of 48 efficacy-evaluable patients receiving clotrimazole, 500 mg (90%), versus 42 of 47 efficacy-evaluable patients receiving clotrimazole, 200 mg (89%). Similarly, at visit 3, 75% of patients receiving clotrimazole, 500 mg, had treatment success versus 72% receiving clotrimazole, 200 mg. There were no significant intergroup treatment differences, indicating that single-dose treatment with clotrimazole, 500 mg, is equipotent to the multidose regimen.

Adolescent↗

Trypanosoma brucei: differentiation of in vitro-grown bloodstream trypomastigotes into procyclic forms.

Trypanosoma brucei strain 366D trypomastigotes grown at 37 degrees C in the presence of a human fibroblast cell line formed foci underneath the feeder cells whereas trypanosomes grown in the presence of a human epithelial cell line grew only in the culture supernatant. A culture system was developed to study the differentiation of bloodstream trypomastigotes grown in the epithelial cell system into procyclic trypomastigotes at 27 degrees C. The morphological differentiation into the procyclic form was complete by 48 h. Cell division did not occur until 30-40 h after transfer to 27 degrees C. Various characteristics of this system were examined, including the effect of the feeder layer, the type of medium, the presence of the metabolites cis-aconitate and citrate, the preadaptation period, and the trypanosome cell concentration. The respiration of the recently differentiated procyclic cells was less sensitive to inhibition by CN- than that of established procyclic forms, implying a delayed appearance of complete mitochondrial oxidative pathways. This trypanosome differentiation system has the advantage that the animal host is not needed and the entire process is carried out in in vitro culture.

Aconitic Acid↗

Autonomous replication sequences in the maxicircle kinetoplast DNA of Leishmania tarentolae.

Four fragments from the maxicircle DNA of Leishmania tarentolae cloned into the selectable Saccharomyces cerevisiae shuttle vector, YIp5, exhibited autonomous replicating sequence (ars) activity. Two of the fragments (pSK120, pSK152) produced large yeast transformant colonies and two (pSK30, pSK150) produced small colonies. All yeast transformants contained extrachromosomal self replicating YIp5 hybrid plasmids as shown by mitotic instability in non selective medium and by the transformation of Escherichia coli with yeast minilysates and recovery of the plasmid from the transformed bacteria. The copy numbers of pSK30, pSK150 and pSK152 in the transformed yeast were approximately the same as that of the YRp12 control, which contains the yeast arsl element; the copy number of pSK120, however, was at least 10 fold lower. A 1.87 kb subfragment of the pSK120 fragment also showed strong ars activity. The entire DNA sequences of the pSK120, pSK152 and pSK150 fragments are known, and several yeast 11 mer consensus ars sequences are present within each fragment. In addition there is a sequence (Lt ars 189) within the pSK152 subclone that has 78% similarity with a 189 nt sequence of an ars element from the Crithidia fasciculata maxicircle (Cf ars 189), implying an evolutionary conservation of this putative origin of replication in at least two different kinetoplastid species. The relative positions of the Lt ars 189 sequence in the L. tarentolae maxicircle map and the Cf ars 189 sequence in the C. fasciculata map with respect to the 9 and 12 S ribosomal genes are similar, implying an overall conservation of gene order in this portion of the transcribed regions of these two species and perhaps in all kinetoplastid species.

Animals↗

Sequence heterogeneity and anomalous electrophoretic mobility of kinetoplast minicircle DNA from Leishmania tarentolae.

Several unit-length minicircles from the kinetoplast DNA of Leishmania tarentolae were cloned into pBR322 and into M13 phage vectors. The complete nucleotide sequences of three different partially homologous minicircles were obtained. The molecules contained a region of approx. 80% sequence homology extending for 160-270 bp and a region unique to each minicircle . A 14-mer was found to be conserved in all kinetoplast minicircle sequences reported to date. The frequency distributions of various minicircle sequence classes in L. tarentolae were obtained by quantitative gel electrophoresis and by examination of the "T ladder" patterns of minicircles randomly cloned into M13 at several sites. By these methods we could assign approx. 50% of the total minicircle DNA into a minimum of five sequence classes. A sequence-dependent polyacrylamide gel migration abnormality was observed with several minicircle fragments both cloned and uncloned. The abnormality was dependent on the presence of a portion of the conserved region of the minicircle .

Animals↗

The effect of oxygen on sleep, blood gases, and ventilation in cystic fibrosis.

We determined the effect of nocturnal low-flow oxygen (NLFO) on arterial oxygen saturation (SaO2), transcutaneous PCO2 (TcPCO2), and sleep quality in 10 patients with cystic fibrosis (CF) and severe stable chronic obstructive pulmonary disease (COPD). The patients were studied on 2 nights, 1 with oxygen and 1 with air at 2 L/min. The NLFO had no effect upon sleep quality in our patients. The minimal SaO2 occurred during REM sleep and averaged 79.4%. With NLFO, this improved to 92.7%. The average maximal rise in TcPCO2 was 5.6 mmHg on falling asleep while breathing air; this increased a further 5.1 mmHg with NLFO. Two patients also had obstructive sleep apnea. Their SaO2 improved dramatically with NLFO, with no deterioration of ventilation. In 4 patients, ventilation was measured quantitatively. The only consistent changes during air were an increase in abdominal contribution to tidal volume and a drop in minute ventilation from Stage 3-4 to REM sleep of 26%, almost entirely caused by a drop in breathing frequency. The same changes occurred with NLFO. We conclude that NLFO is effective in alleviating the nocturnal hypoxemia of patients with CF with stable COPD and does not cause clinically important hypercapnia.

Adolescent↗

Treatment of vulvovaginal candidiasis with a 500-mg vaginal tablet of clotrimazole.

A prospective, randomized, double-blind trial compared the efficacy and safety of a new one-dose clotrimazole regimen and placebo. Twenty-six patients with clinically and mycologically proven vulvovaginal candidiasis received either a 500-mg tablet of clotrimazole or a placebo. Follow-up visits were performed approximately one week and one month after treatment. Efficacy was evaluated in 23 patients. There was a highly significant difference in clinical and mycological responses to the two regimens (P = 0.0001, Fisher's exact test). Nine (90%) of the ten patients in the clotrimazole group showed mycological and clinical clearance of infection one month after treatment, while all 13 patients who had received placebo were classified as treatment failures at the first follow-up visit and were dropped from the study at this point. No patients experienced adverse effects attributable to clotrimazole or the placebo. The findings indicate that a single 500-mg tablet of clotrimazole is effective and safe in the treatment of vaginal candidiasis and suggest that the efficacy and safety of the one-dose regimen are comparable to those of more prolonged courses with the 100-mg tablet of clotrimazole. The convenient one-dose regimen promises to eliminate the widespread problem of patient noncompliance, especially when the tablet is inserted by the physician at the time of diagnosis.

Adolescent↗

Joint protection.

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Activities of Daily Living↗

Malposition of a transvenous cardiac electrode associated with amaurosis fugax.

A 55-year-old male received a transvenous ventricular pacemaker for sick sinus syndrome. After pacemaker insertion, he developed recurrent episodes of amaurosis fugax. The source of thromboemboli was the pacemaker electrode malpositioned in the left ventricle. Position of the electrode was diagnosed correctly by two-dimensional echocardiography. The malpositioned electrode was successfully removed with cessation of recurrent thromboembolic phenomenon.

Blindness↗

Partial and complete maximum expiratory flow-volume curves in asthmatic patients with spontaneous bronchospasm.

Bronchodilatation follows a deep inspiration in normal subjects with pharmacologically induced bronchoconstriction. To determine to what extent this occurs in asthmatic patients with spontaneous bronchospasm, we obtained partial (PEFV) and complete (MEFV) maximum expiratory flow volume curves in 20 adults (helium-oxygen responders and nonresponders) and 13 children with asthma. We measured maximum expiratory flow at 25 percent of forced vital capacity from the partial (Vmax - p) and complete (Vmax - c) flow-volume curves and expressed this relationship as the Vmax - p/Vmax - c ratio. Three of the adult subjects and one of the children had a V max-p/V max-c less than 1.0. Following inhalation of nebulized bronchodilators, none of the children or adults had a Vmax - p/Vmax - c ratio less than 1.0. Reasons for Vmax - p to be higher than Vmax - c include bronchoconstriction, decreased lung elastic recoil following a deep inspiration, and time dependence of maximum expiratory flow due to lung inhomogeneity. We conclude that asthmatic patients with spontaneous bronchospasm are only seldom able to obtain bronchodilation following a deep inspiration.

Adolescent↗

Consultation length and outcome in two group general practices.

Two group general practices were located which, while similar in a number of important respects, differed in the number of appointment consultations arranged per hour, and data was collected to see if corresponding differences in consultation outcome could be found. Information on all appointment consultations offered during a four-week period was analysed, and the number of patients returning for further attention in a subsequent four-week period was also determined. The practice offering longer consultations had a lower proportion of appointment consultations ending with a prescription, required a lower proportion of patients to return for a follow-up appointment, and had a lower proportion of patients themselves returning to seek a further appointment within four weeks of presenting with a new illness episode.

Appointments and Schedules↗

Lack of mature B cells in nude mice with X-linked immune deficiency.

Mice were bred that simultaneously expressed the mutations nude and x-linked immune deficiency (xid). These doubly deficient animals had less than 10% of normal serum immunoglobulin levels. Their spleen cells did not respond to thymus-independent antigens in vitro nor did they respond to lipopolysaccharide. There was a virtual absence of cells with surface mu, kappa, or lambda 1, as detected by fluorescence. Sections of lymphoid organs revealed an absence of primary B cell follicles. Taken together, these results indicate a lack of mature B cells in nude xid mice. The possibility is considered that mature B cells belong to two subpopulations representing two lineages, one controlled by alleles at the xid locus and the other by alleles at the nude locus.

Agammaglobulinemia↗