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[Arrest of lactation after 2nd trimester abortion with a single dose of cabergoline in comparison with 10-day administration of teguride].

OBJECTIVE: The objective of the work was to compare the effectiveness and tolerance of a single administration of 1 mg cabergoline and 10-day administration of 1.5 mg terguride divided into three doses after 8-hour intervals, in the indication of arrest of lactation after an abortion during the second trimester. TYPE OF STUDY: Prospective clinical study. NAME AND PLACE OF DEPARTMENT: Gynaecological and Obstetric Clinic. First Medical Faculty Charles University and General Faculty Hospital Prague, Apolinárská 18, Prague 2. METHOD: During the period between January and October 2000 to 41 patients after abortion induced during the 2nd trimester terguride, 0.5 mg after 8-hour intervals, was administered for a 10-day period. During the subsequent period from November 2000 to September 2001 to 43 patients cabergoline was administered in a single dose within 12 hours after the abortion. During hospitalization the patients were asked daily for their subjective evaluation of the effect of treatment (vertigo, palpitations, headache, nausea, vomiting, abdominal pain, sleepiness, secretion from the breast, tension in the breasts) and the doctor evaluated the success of treatment objectively. Within 21 days after the abortion the patients were addressed over the phone on subjective and objective effects of treatment. For statistical evaluation Fisher's exact bilateral test was used. RESULTS: The "cabergoline" group displayed, as compared with the "terguride" group, significantly fewer undesirable effects (p < 0.01). No significant difference was found between groups (p = 0.1) as regards the necessity to repeat administration of the drug. None of the undesirable effects were so serious to call for interruption of treatment. CONCLUSION: Arrest of lactation during the second trimester of gestation is an integral part of care of the patient. Symptoms associated with lactation are adversely accepted by the patient. The incidence of undesirable effects after a single dose of cabergoline is significantly lower as compared with 10-day administration of terguride. A single dose of cabergoline during hospitalization improves the patients' compliance and thus the effect of treatment. Cabergoline can be used as the drug of first choice for arrest of lactation after abortion during the second trimester of pregnancy.

Abortion, Induced↗

[Social consequences of birth in adolescents].

234 Austrian women gave birth to a child in the years 1972--74 before the age of 18. 95 of them were invited to an interview and interrogated about changes in their life-situation due to the birth. The general attitude was, if they could choose again the date of the first pregnancy they would prefer after 20 years. No correlation was found between early menarche and early sexual intercourse. For 60 of the women pregnancy was the reason for their marriage. Most of the young women had experience with contraceptives, but did not use them for different reasons. After the birth of the child most of them took the pill, but there are 11 women left without any contraception, exposing themselves to the risk of a repeat pregnancy. Young age at birth has an impact upon pre-vocational training: either through interruption of the training or through total discontinuation of their education. A possible solution of the present unsatisfactory situation for young pregnant women and their social problems are interdisciplinary projects for the guidance of adolescents in some centers in the USA.

Adolescent↗

cDNA cloning of two splice variants of a human copper-containing monoamine oxidase pseudogene containing a dimeric Alu repeat sequence.

Two alternatively spliced transcripts, psiHLAO1 and psiHLAO2, of a copper-containing monoamine oxidase pseudogene have been isolated from a human-liver cDNA library. The larger psiHLAO1 cDNA (2073bp) contains a 5'-flanking segment of 134bp, followed by an apparent open reading frame (ORF) of 1725bp. The deduced amino acid sequence of this ORF (574 residues) shares 81.0% similarity with the 763-residue monoamine oxidase from human placenta (HPAO) (the N-terminal 533 residues of psiHLAO1 share 86.7% similarity with HPAO). The psiHLAO1 ORF is interrupted by an in-frame stop codon corresponding to amino acid 225 and terminates within a type S(a) dimeric Alu repeat sequence. psiHLAO2 appears to be an alternatively spliced variant of psiHLAO1 that has 413 bases of psiHLAO1 excised according to the 'GT-AG' rule. The slightly longer 3' end of the psiHLAO2 transcript shows that the Alu repeat is followed by an 11-bp poly(A) tract that, in turn, is followed by an AT-rich (81%) sequence of 105bp. A reverse transcriptase-polymerase chain reaction (RT-PCR) protocol was used to confirm that both psiHLAO1 and psiHLAO2 are transcribed in human liver and placenta. A search of the expressed sequence tag (EST) database indicates that, like HPAO, psiHLAO derives also from the region 17q21 of the human genome.

Alternative Splicing↗

Structure of the human sialophorin (CD43) gene. Identification of features atypical of genes encoding integral membrane proteins.

A human sialophorin (CD43) specific genomic clone was isolated, and a 6.5 kb fragment containing the 4.6 kb sialophorin gene was sequenced. The promoter region contains no TATA or CAAT boxes, but is highly enriched in G and C nucleotides and contains short repeat sequences similar to those found in the promoters of 'housekeeping' genes. S1-nuclease protection and primer-extension experiments established that the sialophorin gene has two major transcription initiation sites. There is a single intron of 378 bp that interrupts the sequence specifying the mRNA 5' untranslated region. The gene is therefore unusual in that the discrete extracellular, transmembrane and intracellular regions of the protein, including repeat sequences in the extracellular region, are not encoded by separate exons. Utilization of alternative polyadenylation signals was previously shown to generate two sialophorin mRNAs of 1.9 and 4.3 kb, which differ in the length of their 3' untranslated regions. Sequence analysis of the gene establishes that a single polyadenylation signal 2301 bp downstream of the first major transcription initiation site and five overlapping polyadenylation signals beginning a further 2290 bp downstream define the 3' termini of the 1.9 and 4.3 kb mRNA species respectively. The gene contains potential Z-DNA structures, Aly sequences, and elements that may be involved in regulating mRNA stability.

Amino Acid Sequence↗

The polymorphic integumentary mucin B.1 from Xenopus laevis contains the short consensus repeat.

The frog integumentary mucin B.1 (FIM-B.1), discovered by molecular cloning, contains a cysteine-rich C-terminal domain which is homologous with von Willebrand factor. With the help of the polymerase chain reaction, we now characterize a contiguous region 5' to the von Willebrand factor domain containing the short consensus repeat typical of many proteins from the complement system. Multiple transcripts have been cloned, which originate from a single animal and differ by a variable number of tandem repeats (rep-33 sequences). These different transcripts probably originate solely from two genes and are generated presumably by alternative splicing of an huge array of functional cassettes. This model is supported by analysis of genomic FIM-B.1 sequences from Xenopus laevis. Here, rep-33 sequences are arranged in an interrupted array of individual units. Additionally, results of Southern analysis revealed genetic polymorphism between different animals which is predicted to be within the tandem repeats. A first investigation of the predicted mucins with the help of a specific antibody against a synthetic peptide determined the molecular mass of FIM-B.1 to greater than 200 kDa. Here again, genetic polymorphism between different animals is detected.

Amino Acid Sequence↗

Genes and pseudogenes for human U2 RNA. Implications for the mechanism of pseudogene formation.

Three loci, designated U2/4, U2/6 and U2/7, which contain sequences related to human U2 RNA, have been studied. The U2/6 locus contains a tandem array of bona fide U2 genes. U2/4 and U2/7, in contrast, contain pseudogenes of whose sequences deviate significantly from that of mammalian U2 RNA. The two pseudogenes appear to have been created by different mechanisms. The sequences that flank the pseudogene in the U2/4 locus lack homology to the corresponding sequences in functional human U2 genes, except for 10 base-pairs immediately following the 3' end. The conserved 3'-flanking segment is homologous to those nucleotides that are present in a U2 RNA precursor. No direct repeats flank the pseudogene in the U2/4 locus. The observations thus suggest that a complementary DNA copy of the U2 RNA precursor was inserted into a blunt-ended chromosomal break to generate the U2/4 locus. The U2/7 locus, in contrast, revealed flanking sequence homology when compared to functional U2 genes, both on the 5' and 3' sides of the pseudogene. The homology was interrupted on both sides by repetitive sequences belonging to the Alu family. On the 5' side the homology continues beyond the Alu repeats whereas on the 3' side it ends precisely at the Alu repeat. This Alu repeat is inserted in a region where a homocopolymeric region of alternating C and T residues is located in functional U2 loci. The observed organization of the U2/7 locus suggests that a previously functional U2 locus was invaded by Alu repeats and subsequently accumulated base substitutions to become a pseudogene.

Base Sequence↗

Rapid eye movement sleep deprivation: a central-neural change during wakefulness.

Three adult cats were deprived of rapid eye movement sleep for six separate periods of up to 32 days. Animals were allowed normal amouints of sleeping time during which rapid eye movement sleep was interrupted, whenever it occurred, by human observers who continually monitored the animals and their electrocortical activity. Cortical responses evoked by pairs of acoustic clicks were recorded during wakefulness. Recovery functions derived from these data were facilitated during periods of deprivation of rapid eye movement sleep and returned to base-line values when animals were allowed normal amounts of this sleep phase. This change was noted repeatedly within, as well as between, subjects. It did not occur during control periods when non-rapid eye movement sleep was interrupted on identical schedules, nor did it occur when the cats were deprived of all sleep for 22 hours a day for 5 days.

Animals↗

Structural changes in the tympanic membrane after repeated tympanostomy tube insertion.

In an animal model (rat) a polyethylene tympanostomy tube was repeatedly inserted (four periods lasting 2 weeks) into the upper rear quadrant of the right tympanic membrane (TM). The intervals between the different tubulation periods (TPs) lasted 3 weeks. The corresponding quadrant of the left TM was subjected to repeated myringotomies (four times). The structural changes in the TMs were evaluated otomicroscopically and by histological techniques 3 weeks and 3 months after the final TP. Repeated tympanostomy tube insertion caused a dramatically thickened pars tensa. The thickened areas were characterized by a scar tissue exhibiting sclerotic plaques and a dense connective tissue with bone-like formations. Occasionally, islands of keratinizing stratified squamous epithelium were noted within the thickened pars tensa as well as interrupting the epithelial lining facing the tympanic cavity. Similar structural changes occurred after myringotomy without tube insertion, but they were not so pronounced as after repeated tympanostomy tube insertion. The changes were not restricted to the manipulated quadrants, but also affected the untouched anterior quadrants. Throughout the observation period the anterior quadrants improved, while the rear quadrants remained severely affected.

Animals↗

[Rescreening study of the population of the endemic village Gorno Peshtene, Vrachansk].

The number of the recorded patients with Balkan endemic nephropathy gradually decreased during the period after 1970. The author explains that by the interrupted prophylactic examinations and screenings of the population from the endemic villages during that period. The results obtained with the repeated screening, after 16 years, of the population of one hyperendemic village in Vratza district support that view point. New 74 patients with Balkan endemic nephropathy were found, 8 of them with uroepithelial tumours of the upper urinary pathways. Together with the 45 patients known so far, their total number amounts to 119, suggesting that 13,7 per cent of the population from that village has been affected by the disease. Those data convincingly suggest that the morbidity rate from Balkan endemic nephropathy in our country has not decreased - only its recording has been neglected, due to the interruption of the active search of those patients via screening of the population from the endemic settlements. That emphasizes the great importance of those investigation methods in the establishment of the real Balkan endemic nephropathy morbidity.

Adolescent↗

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains.

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub-domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non-homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.

Base Sequence↗

Repeated withdrawal from ethanol on radial arm acquisition in rats.

Male rats were treated with ethanol (8.0-12.0 g/kg/day) for four 2 week periods interrupted every 2 weeks by a 2 week period of no drug treatment. Thus they experienced withdrawal from ethanol four times. Other rats were treated with ethanol for 8 weeks with no interruptions, to control for the total dose and duration of drug treatment. Acquisition of an eight-arm radial maze response when daily ethanol treatment was ended, was not affected by either the experience of four withdrawals from ethanol or by 8 weeks of ethanol treatment. The lack of withdrawal-induced impairment can be attributed to a lack of sensitivity in the maze task to possible withdrawal-induced deficits and to an insufficient duration of ethanol dependence.

Alcoholism↗

[Dinoprostone or sulprostone. Comparison of 2 analogs of prostaglandin for the interruption of pregnancy in the 2nd trimester].

We have reviewed a hundred terminations of pregnancy in the second trimester carried out in Geneva, using repeated intra-muscular injections of prostaglandin analogues. We have compared the efficacy and the importance of the side effects of two of these analogues, namely Dinoproston ( Prostin F2 alpha) and Sulproston ( Nalador 500). The induction-delivery interval was identically the same. On the other hand Sulproston provoked fewer cases of diarrhoea (18%) than Dinoproston (69%).

Abortifacient Agents↗

Structure, organization and evolution of developmentally regulated chorion genes in a silkmoth.

We describe in detail two cloned chromosomal DNA segments from Antheraea polyphemus, each bearing multiple chorion genes. Two types of genes are found per segment, each in two or three copies: they belong to both major chorion multigene families (A and B), but are expressed during the same developmental period (middle choriongenesis in one segment, late in the other). A and B genes alternate and are paired, lie in divergent transcriptional orientation and are in very close proximity to each other (mRNA cap sites are separated by a 5' flanking sequence 264 or 325 bp long). Each AB pair is embedded within a large, tandemly repeating unit. Within that unit, the homologous 3' flanking sequences that separate gene pairs evolve rapidly and are frequently interrupted by long segments representing inserts (or deletions). These segments would decrease unequal crossing-over, facilitating rapid evolution of the chorion multigene families. A total of 10.4 kb of DNA has been sequenced, permitting detailed comparisons of genes, their introns, 5' flanking and immediately 3' flanking regions. Genes range over two orders of sequence similarity, from highly releated to very disparate (gene copies; members of the same multigene family; members of different families). Among their universal features are a common cap-site sequence, a single intron invariably located at the same position within the signal peptide-encoding region, and a Hogness box 21 to 23 nucleotides upstream from the cap site. Features of possible paired promoters occupying the short 5' flanking region are discussed. Genes evolve both by base substitutions and by segmental mutations, which are almost invariably deletions/insertions related to small, direct repeats.

Animals↗

Thoracoscopic sympathicolysis for essential hyperhidrosis: effects on pulmonary function.

Bilateral interruption of the upper dorsal sympathetic chain at the D2 and D3 level represents the only permanent cure for essential hyperhidrosis. Following surgical sympathectomy, significant and symptomatic changes in pulmonary function have been observed. Since functional effects of the surgical intervention cannot be excluded, we wondered whether such alterations also occurred after thoracoscopic sympathicolysis; these should then be attributable to the surgical denervation itself. Pulmonary function tests (PFTs), including spirometry and body plethysmographic measurement of lung volumes and airway resistance and conductance, were compared before and 6 weeks after thoracoscopic sympathicolysis in 47 patients. In order to virtually exclude any effects of thoracoscopy on the test results PFTs were repeated 6 months after thoracoscopic sympathicolysis in 35 patients. Essential hyperhidrosis was completely relieved in all patients, thereby confirming the interruption of the D2-D3 sympathetic chain. None of the patients developed respiratory symptoms after thoracoscopic sympathicolysis. Forced expiratory volume in one second (FEV1) (-3%), forced expiratory flow after exhaling 75% of vital capacity (FEF75) (-8%) and total lung capacity (TLC) (-3%) were slightly but significantly reduced at six weeks after thoracoscopic sympathicolysis; whereas airway resistance (Raw) had increased (+12%). After correction for the small decrease in lung volume (FEV1/forced vital capacity (FVC), specific airway resistance (sRaw), specific airway conductance (sGaw))significant changes in "volume-dependent" PFT parameters were no longer observed. Smoking status had no influence on the reduction in FEF75. At 6 months after thoracoscopic sympathicolysis, TLC had returned to preoperative values, whereas FEF75 remained decreased (-8.6%). The decrease in airway calibre was confirmed by small but significant changes in FEV1/FVC (-2%) and Raw (+29%). We conclude that thoracoscopic sympathicolysis in patients with essential hyperhidrosis causes only minimal and subclinical changes in pulmonary function secondary to a temporary small decrease in lung volume, which in turn is probably inherent to the thoracoscopic procedure. D2-D3 sympathicolysis, in itself, is responsible only for a small and permanent decrease in forced expiratory flow, which suggests that, at least in essential hyperhidrosis patients, airway bronchomotor tone is influenced by sympathetic innervation.

Adolescent↗

Macroevolution by transposition: drastic modification of DNA recognition by a type I restriction enzyme following Tn5 transposition.

We have characterized a novel mutant of EcoDXXI, a type IC DNA restriction and modification (R-M) system, in which the specificity has been altered due to a Tn5 insertion into the middle of hsdS, the gene which encodes the polypeptide that confers DNA sequence specificity to both the restriction and the modification reactions. Like other type I enzymes, the wild type EcoDXXI recognizes a sequence composed of two asymmetrical half sites separated by a spacer region: TCA(N7)RTTC. Purification of the EcoDXXI mutant methylase and subsequent in vitro DNA methylation assays identified the mutant recognition sequence as an interrupted palindrome, TCA(N8)TGA, in which the 5' half site of the wild type site is repeated in inverse orientation. The additional base pair in the non-specific spacer of the mutant recognition sequence maintains the proper spacing between the two methylatable adenine groups. Sequencing of both the wild type and mutant EcoDXXI hsdS genes showed that the Tn5 insertion occurred at nucleotide 673 of the 1221 bp gene. This effectively deletes the entire carboxyl-terminal DNA binding domain which recognizes the 3' half of the EcoDXXI binding site. The truncated hsdS gene still encodes both the amino-terminal DNA binding domain and the conserved repeated sequence that defines the length of the recognition site spacer region. We propose that the EcoDXXI mutant methylase utilizes two truncated hsdS subunits to recognize its binding site. The implications of this finding in terms of subunit interactions and the malleability of the type I R-M systems will be discussed.

Base Sequence↗

Identification of two sequence elements associated with the gene encoding the 24-kDa crystalline component in Bacillus thuringiensis ssp. fukuokaensis: an example of transposable element archaeology.

A 6.5-kb fragment of plasmid DNA from Bacillus thuringiensis (Bt) ssp. fukuokaensis that encodes a 24-kDa crystalline component was analyzed to identify additional open reading frames (orfs). A novel Bt IS240-like element was found upstream of this gene and is considered to be a vestige of a once active insertion sequence due to a stop codon that interrupts the long orf encoding the putative transposase. This element was bounded by 17-bp terminal inverted repeats that defined the length of the insertion sequence as 802 bp. Further upstream of this element two tandem overlapping and out of phase open reading frames (orfX and orfY) were identified which represent the first example of an IS150-like element in Bt containing both orfs. orfX and orfY are not bounded by terminal inverted repeats but are associated with a gene encoding a putative site-specific recombinase of a type found in Staphylococcus aureus Class II transposons but not previously in Bt.

Amino Acid Sequence↗

[Lithostar Multiline. A multi-function lithotripter for ESWL and endourology: initial clinical experiences].

After > 10,000 treatments-our HM3/4 and MPL 9000 have been replaced by the Siemens Lithostar multiline. As a ESWL center with ESWL as the primary treatment indication for all types of stones in kidney and ureter we report our initial experience with this new multifunctional lithotripter. The system consists of an electromagnetic shock-wave emitter (Focus 80 x 5 mm) and a digital fluoroscopy unit. Stone localization is achieved in a - 10 degrees and + 30 degrees position without movement of the patient. The treatment table itself allows most endourologic and percutaneous auxiliary procedures. Additionally, an intergrated inline ultrasound is available. From 10/94 to 08/95, 204 male and 96 female patients with a mean age of 50.7 (4-92) years underwent ESWL with the Lithostar multiline. The mean stone diameter was 10.3 (2-20) mm with 53% ureteral and 47% renal stones. 300 patients underwent 480 treatments (average shocks 3673, range 793-8000; mean energy level 5.5, range 1-9). Stone localization was achieved after 5 (1-39) min (mean fluoroscopy time 3.1 (0.5-16.2) min). In 92.7% no analgesic premedication was done, 56% of the patients needed no analgesics at all during ESWL. 44% received 8.1 (2-15) mg Piritramid intravenously. Epidural anesthesia was performed in only 2.3% for a second treatment. 95% of the patients had complete stone disintegration. In 68% disintegration was achieved in one session. ESWL was repeated for further disintegration in 18.5%, because of an unsuccessful treatment in 11.5% and because of technical interruption of the previous session in 2.5%. We saw subkapsular haematomas in 2%. Auxiliary procedures following ESWL were necessary in only 9.2% of the patients. In situ ESWL with the new Lithostar Multiline seems to be effective as the Domler HM3/4. Analgesia-free treatment was performed in more than 50% of the patients. Auxiliary procedures were less frequently necessary as compared to our previous experience with in situ ESWL.

Adolescent↗

Features of the mammal mar1 transposons in the human, sheep, cow, and mouse genomes and implications for their evolution.

Mariner-like elements (MLE) belong to the Tc1/ mariner superfamily of class II transposons. We have analyzed the mariner related to the cecropia subfamily, and called mammal mar1, in four mammalian genomes, Bos taurus (Bovidae), Homo sapiens (Primata), Mus musculus (Rodentia), and Ovis aries (Ovidae). Three kinds of MLE sequences were found in all these species: full-length 1.3-kbp elements, shorter elements 80 bp-1.2 kbp, and single inverted terminal repeats (ITRs). All the 1.3-kbp genomic copies sequenced had an open reading frame encoding a transposase interrupted by stop codons or frame shifts. Phylogenetic analysis of the full-length elements suggested at least two distinct populations of mammal mar1 elements in each species. This was confirmed by using a statistical method that allows defining populations. Finally, the evolutionary origin of the mammal mar1 elements and the paradoxes are discussed.

Animals↗