Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

The effect of training intensity on ratings of perceived exertion.

We examined the effects of intensity of training on ratings of perceived exertion (RPE) at the lactate threshold (LT), fixed blood lactate concentrations (FBLC) of 2.0, 2.5 and 4.0 mM and peak in 25 untrained eumenorrheic women (mean +/- SD: age = 30.9 +/- 4.1 yrs; height = 165.7 +/- 5.9 cm; weight = 65.5 +/- 7.6 kg) who completed one year of run training. Subjects were recruited as sedentary controls or were randomly assigned to one of two training groups: 1) at the lactate threshold (at LT) or 2) above the lactate threshold (greater than LT). The at LT group trained at velocity LT and the greater than LT group trained at the velocity midway between velocity LT and peak velocity. Training subjects were reevaluated every fourth menstrual cycle and training intensity was adjusted. The control group was reassessed at menstrual cycle 12. Before training no among group differences were observed for VO2 or velocity at LT, FBLC and peak. Both training groups increased VO2 at LT, FBLC and peak as a result of training (p less than 0.05), with the greater than LT group exhibiting greater improvement than the at LT group (VO2 at LT, FBLC of 2.0, 2.5 and 4.0 mM and peak increased by 6.4, 5.3, 5.1, 4.0 and 4.7 ml/kg.min-1 for at LT and by 10.4, 9.2, 8.6, 5.1 and 5.9 ml/kg.min-1 for greater than LT; p less than 0.05). Similar findings were observed for the velocity associated with these lactate concentrations. No pre/post differences were observed in VO2 or velocity for the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.      

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Heart period variability of trained and untrained men at rest and during mental challenge

The effect of aerobic training on parasympathetic reactivity to mental stress is unclear. Thus, the parasympathetic response, as assessed by time series analysis of heart period variability (HPV_ts), of 10 trained male runners (trained group), 10 inherently low resting heart rate untrained men (low HR group), and 10 normal resting HR men (control group) at rest and to two mental stressors was examined. Participants completed a mental arithmetic and Stroop task. Resting HPV_ts at high and medium frequencies was significantly greater for the trained and the low HR groups than for the control group. Significantly greater decreases in HPV_ts at the medium frequency during arithmetic recovery were measured for the trained and low HR groups compared with the response of the control group. Significantly greater decreases in HPV_ts at both the the high and medium frequencies during the first two epochs of the Stroop occurred only for the trained and low HR groups. These results suggest that the greater HPV_ts at rest and decline in HPV_ts during and after mental challenge is influenced by both aerobic training and genetic inheritance.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

In vitro susceptibility of Ureaplasma urealyticum and Mycoplasma hominis isolates in Argentina

Objective: Our goal was to determine the in vitro susceptibility of Ureaplasma urealyticum and Mycoplasma hominis isolates to several antibiotics in Argentina.Methods: Ninety-four strains of U. urealyticum and 18 strains of M. hominis isolated from cervical and urethral specimens were studied. Broth microdilution and agar dilution tests for minocycline, tetracycline, erythromycin, ciprofloxacin, and ofloxacin were performed.Results: Both methods proved to be reliable and reproducible for U. urealyticum and M. hominis, with no major differences in results. The U. urealyticurn strains were inhibited by erythromycin at MICs ranging from 8 mu/ml. Ofloxacin showed the highest activity against this latter organism. No differences between tetracycline and minocycline MICs were observed with U. urealyticum. Two M. hominis strains displaying high MICs both to tetracycline and to minocycline were detected.Conclusions: The emerging resistance of mycoplasmas to certain antibiotics emphasizes the need to undertake further surveillance studies on the clinical isolates of such organisms.