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[Acute renal failure, intravascular hemolysis and toxic hepatitis caused by repeated use of rifampicin (case report)].

We report the case of a 57-year-old man treated with interrupted rifampicin therapy for urinary tract tuberculosis who experienced acute renal failure, intravascular hemolysis and toxic hepatitis. This combined adverse reactions are rare. Supportive treatment with dialysis and withdrawal of rifampicin result with complete recovery. Interrupted and intermittent therapy with rifampicin should be avoided and noncompliant patients should be given alternative treatment when possible.

Acute Kidney Injury↗

Population variation analysis at nine loci containing expressed trinucleotide repeats.

The polymorphisms of nine loci containing reiterated CAG repeats were examined in four populations from three continents. Their normal variation was analysed across populations or in subsets of loci grouped according to either the presence/absence of disease-associated expansions or CAG interruptions. A unifying feature of the allele distributions of all loci in all populations was the marked non-normality. Significantly larger numbers of alleles, average lengths, length ranges and variances in repeat number were observed in loci with vs. without known expansions. Significantly longer alleles were found at loci with vs. without interruption of the (CAG)n motif. The nine loci detected levels of inter-population variability comparable to other loci. Altogether the data are at odds with a model assuming that autosomal expressed trinucleotides accumulate variation exclusively by insertion/deletion of a single unit.

Alleles↗

Repeat-type distribution in trnL intron does not correspond with species phylogeny: comparison of the genetic markers 16S rRNA and trnL intron in heterocystous cyanobacteria.

tRNA(Leu) UAA (trnL) intron sequences are used as genetic markers for differentiating cyanobacteria and for constructing phylogenies, since the introns are thought to be more variable among close relatives than is the 16S rRNA gene, the conventional phylogenetic marker. The evolution of trnL intron sequences and their utility as a phylogenetic marker were analysed among heterocystous cyanobacteria with maximum-parsimony, maximum-likelihood and Bayesian inference by comparing their evolutionary information to that of the 16S rRNA gene. Trees inferred from the 16S rRNA gene and the distribution of two repeat classes in the P6b stem-loop of the trnL intron were in clear conflict. The results show that, while similar heptanucleotide repeat classes I and II in the P6b stem-loop of the trnL intron could be found among distant relatives, some close relatives harboured different repeat classes with a high sequence difference. Moreover, heptanucleotide repeat class II and other sequences from the P6b stem-loop of the trnL intron interrupted several other intergenic regions in the genomes of heterocystous cyanobacteria. Cluster analyses based on conserved intron sequences without loops P6b, P9 and parts of P5 corresponded in most clades to the 16S rRNA gene phylogeny, although the relationships were not resolved well, according to low bootstrap support. Thus, the hypervariable loop sequences of the trnL intron, especially the P6b stem-loop, cannot be used for phylogenetic analysis and conclusions cannot be drawn about species relationships on the basis of these elements. Evolutionary scenarios are discussed considering the origin of the repeats.

Base Sequence↗

[Small bowel motility in the irritable bowel syndrome].

The presently available methods of study of small bowel motility in humans include manometry (or electromyography) which records the temporospatial organization of bowel contractions and determination of intestinal transit time. Investigation of subjects with the irritable bowel syndrome has shown that the small intestine has its part in the motor disturbances. The characteristics of normal motility of the small intestine are well known: the migrating motor complex (MMC) develops during the interdigestive period, typical contractions are seen during phases 2 and 3 of the MMC, the nature and the duration of the motor response to alimentation have been described. In patients with IBS, the production of the MMC is irregular during the day hours; this is most likely due to environmental solicitations and it is recognized that intensive aliess can cause transient interruption of the development of cycles. On the other hand, the MMC develops normally during sleeping hours. Contraction derangements such as non propulsed repeated contractions in the proximal intestine and contractions propulsed too frequently in the small intestine may be found during phase 2. Some of the abnormal contractions coincide with abdominal pain. After meals, the duration of interruption of the MMC is shorter than in the normal subject. Transit time is shortened in patients with diarrhea, lengthened in patients with constipation. Patients with IBS respond excessively to certain stimuli: for instance, the motor response to cholecystokinin is increased compared to the normal subject. Intake of fatty ingesta is followed by the same type of reaction: pain is often associated with abnormal contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Colonic Diseases, Functional↗

Comparison of rapid bolus instillation with simplified slow administration of surfactant in lung lavaged rats.

The aim of this study was to compare the effects of modified porcine surfactant (Curosurf) given either by a simplified slow delivery technique or by the standard bolus method, on pulmonary gas exchange, lung mechanics, and surfactant distribution in rats with respiratory failure produced by lung lavage. Twelve rats with respiratory failure induced by lung lavage received 200 mg x kg(-1) body weight (b.w.) of tagged porcine surfactant, either by the standard bolus delivery technique or by a simplified 1-min intratracheal infusion method, not requiring interruption of mechanical ventilation. Cardiovascular parameters, arterial blood gases, and pulmonary mechanics were measured repeatedly. Surfactant distribution was also measured by dye-tagged microbead spheres. After surfactant administration, there were no overall major differences between groups in mean heart rate, blood pressure, arterial blood gases, dynamic lung compliance, respiratory system resistance, and pulmonary distribution of exogenous surfactant. However, after 180 min pulmonary gas exchange was better and compliance higher in the bolus than the 1-min infusion group. A transient decrease in blood pressure and heart rate was observed in the bolus group; this side effect was not seen in animals treated with the simplified 1-min infusion method. We conclude that in rats subjected to lung lavage, the infusion of porcine surfactant by a simplified 1-min procedure produced similar short-term effects compared to the same dose of surfactant given by the bolus method. We speculate that tracheal bolus dosing is highly effective and might be the preferable delivery method for porcine surfactant. Dosing by the simplified method described appears less effective, but since no significant differences were observed, and since it produced less acute adverse effects, it could be used when clinical circumstances preclude rapid delivery.

Animals↗

Pituitary response to growth hormone-releasing factor in rats with functional or anatomical lesions of the central nervous system that inhibit endogenous growth hormone secretion.

The pituitary growth hormone (GH) response to the growth hormone-releasing factor, hpGRF-44, was evaluated in male rats with various lesions of the central nervous system. These included an electrical lesion of the ventromedial hypothalamus, a chemical lesion of the arcuate nucleus induced by neonatal treatment with monosodium glutamate, a functional lesion of catecholamine synthesis with alpha-methyl-p-tyrosine or a functional lesion of catecholamine storage with reserpine. The first three lesions appear to partially inhibit normal somatostatin secretion since in every instance hpGRF-44 administration induced a significant increase in plasma GH concentrations. In contrast, reserpine blocked the GH response to hpGRF-44, presumably by stimulating somatostatin secretion. The pituitary GH response to hpGRF-44 in the above described models was enhanced by pretreatment of the rats with antibodies against somatostatin. The pituitary GH response to repeated injections of hpGRF-44 was also evaluated in rats with an anatomical lesion of the arcuate nucleus or a functional lesion of catecholamine synthesis. The maximum GH response did not vary over time to the repeated injections of hpGRF-44 in rats with lesions of the arcuate nucleus; however, interruption of catecholamine synthesis resulted in a significant decrease in the GH response to hpGRF-44 over time.

Animals↗

Positive peak identification in liquid chromatography using absorbance ratioing with a variable-wavelength spectrophotometric detector.

It is frequently necessary to confirm the identification of component peaks isolated in high-performance liquid chromatograms. The UV spectrum of the pure compound is usually a very powerful signature for most compounds. For liquid chromatographic instruments that permit stop-flow operation, a simple approximation is obtained with a variable wavelength UV detector by determining the absorbance ratios at several specific wavelengths to characterize the compound. If the wavelengths are well chosen, these absorbance ratios provide a very specific and a very reliable technique for peak identification. The absorbance ratios are independent of the concentration of the compounds in the detector flow cell. Identity or purity of individual peaks can be confirmed when absorbance ratios are taken from the peaks of individually injected pure standards. Flow can be stopped several times on the leading and trailing edges of broad peaks, and ratios calculated. If the ratios are identical, the peak can be considered to be pure; if ratios differ, the presence of unresolved components can be suspected. Stop-flow ratioing can be performed during gradient elution: standards are injected under rapid elution conditions and the resulting ratios are compared with those of the peaks from the gradient run. Ratios are found to be identical for similar components, regardless of the differences in retention time, thus providing rapid identification of the compounds in the gradient chromatogram. Factors that influence the overall precision of the method are: ability to stop and re-start eluent flow without loss of chromagraphic efficiency, ability to obtain numerical absorbance data from the detector, the wavelength repeatability of the detector, and the requirement that the detector cell design allow slow interruptions without baseline upset.

Chromatography, High Pressure Liquid↗

Effects of tropomyosin internal deletions on thin filament function.

Striated muscle tropomyosin spans seven actin monomers and contains seven quasi-repeating regions with loose sequence similarity. Each region contains a hypothesized actin binding motif. To examine the functions of these regions, full-length tropomyosin was compared with tropomyosin internal deletion mutants spanning either five or four actins. Actin-troponin-tropomyosin filaments lacking tropomyosin regions 2-3 exhibited calcium-sensitive regulation in in vitro motility and myosin S1 ATP hydrolysis experiments, similar to filaments with full-length tropomyosin. In contrast, filaments lacking tropomyosin regions 3-4 were inhibitory to these myosin functions. Deletion of regions 2-4, 3-5, or 4-6 had little effect on tropomyosin binding to actin in the presence of troponin or troponin-Ca(2+), or in the absence of troponin. However, all of these mutants inhibited myosin cycling. Deletion of the quasi-repeating regions diminished the prominent effect of myosin S1 on tropomyosin-actin binding. Interruption of this cooperative, myosin-tropomyosin interaction was least severe for the mutant lacking regions 2-3 and therefore correlated with inhibition of myosin cycling. Regions 3, 4, and 5 each contributed about 1.5 kcal/mol to this process, whereas regions 2 and 6 contributed much less. We suggest that a myosin-induced conformational change in actin facilitates the azimuthal repositioning of tropomyosin which is an essential part of regulation.

Actins↗

Sequence interruptions confer differential stability at microsatellite alleles in mismatch repair-deficient cells.

Determinants of instability at a given microsatellite repeat merits investigation in view of relevance to understanding evolution of mutations at such sequences in human populations. The microsatellite D2S123 was studied as a paradigm CA repeat marker. Furthermore, this marker is one of a recommended panel used in molecular screening for hereditary non-polyposis colorectal cancer (HNPCC). In this investigation we show that the mutation rate at the D2S123 locus is markedly influenced by intra-allelic sequence variation within the repetitive tract itself. We employed a novel approach to characterize the nature of instability at D2S123, by utilizing cells derived from a non-tumour lineage, which harbour a dominant negative mismatch repair (MMR) mutation and a mutator phenotype. Individual alleles were typed using a semi-quantitative small pool PCR technique and this demonstrated substantial allele-these specific bias in susceptibility to mutation at the D2S123 locus. In support of these in vitro data, bias in allele mutation rate was also observed in tumours from 41 HNPCC patients, which was dependent on constitutional genotype. Sequencing of cell line and patient DNAs revealed that short alleles are significantly more susceptible to mutation due to the presence of uninterrupted CA repeats. Long D2S123 alleles are intrinsically more stable because of a TA interspersion within the repetitive tract. In addition to extending understanding of mutation at CA repeat dinucleotide tracts, these findings have considerable relevance both to screening programmes and to correlation of microsatellite instability (MSI) with colon cancer survival. The manifestation of tumour MSI may be substantially influenced by constitutional genotype.

Alleles↗

Hearing threshold shifts from repeated 6-h daily exposure to impact noise.

Exposure of chinchillas to broadband, high-level impact noise on an interrupted 6-h daily schedule over 20 days has shown that pure-tone thresholds measured immediately following each daily exposure improve as much as 30 dB despite the continuing noise exposure. The time constant of this recovery effect (toughening) and the magnitude of the effect are related to the audiometric test frequency and the exposure energy. The trauma, quantified by permanent threshold shifts and sensory cell losses, produced by the interrupted exposure paradigm is generally less than that produced by an equal-energy uninterrupted exposure. The wide variations in the temporal pattern of threshold shift across similarly exposed animals suggest that the toughening effect reflects the underlying susceptibility of that animal to noise trauma.

Animals↗

Nurse telephone triage for same day appointments in general practice: multiple interrupted time series trial of effect on workload and costs.

OBJECTIVE: To compare the workloads of general practitioners and nurses and costs of patient care for nurse telephone triage and standard management of requests for same day appointments in routine primary care. DESIGN: Multiple interrupted time series using sequential introduction of experimental triage system in different sites with repeated measures taken one week in every month for 12 months. SETTING: Three primary care sites in York. PARTICIPANTS: 4685 patients: 1233 in standard management, 3452 in the triage system. All patients requesting same day appointments during study weeks were included in the trial. MAIN OUTCOME MEASURES: Type of consultation (telephone, appointment, or visit), time taken for consultation, presenting complaints, use of services during the month after same day contact, and costs of drugs and same day, follow up, and emergency care. RESULTS: The triage system reduced appointments with general practitioner by 29-44%. Compared with standard management, the triage system had a relative risk (95% confidence interval) of 0.85 (0.72 to 1.00) for home visits, 2.41 (2.08 to 2.80) for telephone care, and 3.79 (3.21 to 4.48) for nurse care. Mean overall time in the triage system was 1.70 minutes longer, but mean general practitioner time was reduced by 2.45 minutes. Routine appointments and nursing time increased, as did out of hours and accident and emergency attendance. Costs did not differ significantly between standard management and triage: mean difference pound 1.48 more per patient for triage (95% confidence interval -0.19 to 3.15). CONCLUSIONS: Triage reduced the number of same day appointments with general practitioners but resulted in busier routine surgeries, increased nursing time, and a small but significant increase in out of hours and accident and emergency attendance. Consequently, triage does not reduce overall costs per patient for managing same day appointments.

Appointments and Schedules↗

Influence of valve surgery on female fertility.

Pregnancies following cardiac valve surgery represent a considerable maternal and fetal risk. The present paper is a report of 163 women in child-bearing age who underwent cardiac valve surgery. Congenital (14.7%) and acquired (85.3%) cardiac defects required a total of 72 alloplastic and 16 bioprosthetic valve implantations. In 69 patients, purely instrumental correction was performed, in 6 patients conduits were placed. Thirty-four pregnancies were observed and led to the delivery of 18 healthy infants. The birth weight was always in the 2-sigma normal range or slightly above. Three cesarean sections were performed due to the cardiac defect, in 6 patients vacuum extraction or forceps delivery was done, and in 9 patients delivery was spontaneous. We observed 4 cases of spontaneous abortion, and in 12 cases interruption of pregnancy. 75.1% women never became pregnant. Potential risks in terms of endocarditis, repeated valve implantation and anticoagulation are emphasized, methods to decrease the physical strain during delivery are discussed.

Bioprosthesis↗

The programmatic hemosorption in the comprehensive treatment of atherosclerosis of various localization. Hemosorption in the treatment of atherosclerosis.

The inclusion of hemosorption through activated coals into the comprehensive treatment of 580 patients sick with atherosclerosis has made it possible to achieve a positive clinical effect among 81 per cent of the patients sick with the ischemic heart disease, 79 per cent of atherosclerotic discirculatory encephalopathy and 76 per cent of obliterating atherosclerosis of lower limbs. The positive dynamics is especially visible among patients who are administered the programmatic hemosorption, making it possible over a long period of time (3-5 years) to sustain remission in the clinical state and the normal level of the lipids in the blood. The direct effect is expressed in the improved microcirculation, disappearance of the sludge-syndrome and the reduction of ischemic disorders. The remote effect of hemosorption is connected with the repeated removals of cholesterin of the atherogenic lipoproteids, which leads, we believe, to the interruption or even regression of the atherosclerotic process.

Arteriosclerosis↗

Tegafur and uracil plus leucovorin in advanced colorectal cancer: a phase II trial.

The objective of this study was to evaluate the activity and toxicity of tegafur and uracil (UFT; 1:4 molar ratio) plus leucovorin (LV) in patients with advanced colorectal cancer. One hundred forty-one patients were entered into the study. The treatment schedule consisted of UFT 300 mg/m2/day (in three divided doses) plus oral LV 150 mg/day (50 mg t.i.d.) over 28 days. The treatment cycle was repeated every 5 weeks until progression or unacceptable toxicity was observed. The treatment was interrupted if grade 3/4 toxicity appeared and was resumed at the same dosage on recovery. One hundred thirty-six patients were evaluable for response and 141 were evaluable for toxicity. The response rate was 19.9% (95% confidence interval: 12%-28%). The total number of patients without progression (objective response + stable disease) was 76 (55.9%). The median time to progression was 5.6 months, and the overall survival was 11.6 months. The toxicity profile was low, with 11% of patients experiencing grade 3/4 nausea and vomiting, while 17% had grade 3/4 diarrhea. Oral administration of UFT modulated with LV is a comfortable regimen of chemotherapy for patients with advanced colorectal cancer.

Administration, Oral↗

[Lithium salts in manic-depressive psychoses (cyclophrenia)].

In psychiatry, lithium salts are used alone, or in combination with neuroleptics, in the treatment of manic states and in the prophylaxis of manic or melancholic relapses in cyclophrenia. They are also used by some clinicians to prevent relapses of melancholia. To be efficient, the blood level of lithium must be between 0,8 and 1,2 mEq/liter in chronic treatment, and much higher in acute treatment. Side effects can be present, but do not warrant to stop the treatment; meanwhile there are signs of intoxication which necessitate immediate treatment interruption. This medication should be given to motivated patients, of normal intelligence, suffering from repeated states of mania or melancholia, because it is a long term treatment requiring constant supervision.

Bipolar Disorder↗

[Sibling relations from the family therapy perspective--support, attachment, rivalry and envy].

In family therapy, during the last years more and more importance is attached to the dynamics of the sibling subsystem. In the present paper differences between them as well as similarities are discussed from the point of view of family theory. Relevant dimensions like support, attachment, rivalry and envy between brothers and sisters contribute essentially to the family dynamics. In this clinically orientated paper, we describe by means of a case example how the couple's conflicts after their separation is unconsciously repeated in the sibling subsystem. It is shown how the intergenerational dynamics can be interrupted by the initiative of the children and the initiated family therapy.

Adolescent↗

[Survival after oozing type cardiac rupture associated with subepicardial aneurysm evaluated by echocardiography: a case report].

A 64-year-old woman was admitted to our hospital with acute myocardial infarction. She underwent emergent percutaneous transluminal coronary angioplasty. Transthoracic echocardiography revealed mild pericardial effusion on the third day. Pericarditis or cardiac rupture were suspected, so transthoracic echocardiography was repeated serially. On the sixth day, transthoracic echocardiography showed increasing pericardial effusion and abrupt interruption of the apical myocardium of the left ventricle and intact epicardial imaging with systolic expansion. The diagnosis was oozing type cardiac rupture of a subepicardial aneurysm. Surgical treatment was successful and the accuracy of the echocardiographic diagnosis was established.

Angioplasty, Balloon, Coronary↗

Localized healing of small intestinal anastomoses.

Small bowel anastomoses were made in a group of adult Sprague-Dawley rats. In another group of animals, interrupted suture of the terminal ileum was performed without transection. The animals were labeled repeatedly by injections of 3H-proline during the second and third week after surgery. Animals were sacrificed at three weeks after anastomosis or suturing. Ten and two mm segments were precisely excised on either side of the anastomoses or suturing. Total collagen and total radioactivity were measured per length of segment. In the small intestine, a similar increase in collagen (four-fold) and its radioactivity (four-fold) occurs only within a centimeter of the anastomotic site, mostly within 0.4 to 0.6 mm. Some of this increase in secondary to the effects of the suture, but most of the increase is due to the anastomosis. The collagen data indicate that the healing of a small intestinal wounds is a local phenomenon.

Animals↗