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.     

Distribution of isoniazid in an overdose death.

A fatality due to the ingestion of isoniazid, a tuberculostatic agent, is presented. Isoniazid was extracted by a single step extraction procedure, derivatized with trifluoroacetic anhydride, and identified and quantified by gas chromatography/mass spectrometry (GC/MS). The distribution of isoniazid was as follows: heart blood 43 mg/L, subclavian blood 94 mg/L, urine 470 mg/L, bile 900 mg/L, liver 650 mg/Kg, kidney 110 mg/Kg, and stomach contents 4 mg.     

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.      

A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling)

Trichotillomania, an irresistible impulse to pull out one's own hair, is a chronic psychiatric illness that causes severe discomfort, interferes with daily activities, and leads to social isolation. Treatment is usually unsatisfactory. Thirteen women with severe trichotillomania completed a 10-week double-blind, crossover trial of clomipramine, a new tricyclic antidepressant agent with selective antiobsessional effects, and desipramine, a standard tricyclic antidepressant. Treatment with clomipramine resulted in significantly greater improvement in symptoms than desipramine, as indicated by physicians' ratings of the women's clinical progress on a scale in which lower scores indicate improvement (mean [+/- SD] scores: at base line, 10.0; after desipramine treatment, 8.7 +/- 2.4; after clomipramine treatment, 4.7 +/- 3.1; P = 0.006) and by scores on a trichotillomania-impairment scale, in which higher scores indicate greater impairment (at base line, 6.8 +/- 1.7; after desipramine treatment, 6.2 +/- 1.7; after clomipramine treatment, 4.2 +/- 2.7; P = 0.03). The severity of symptoms (mean base-line score, 15.9 +/- 3.8) was reduced more by clomipramine (10.6 +/- 6.4) than by desipramine (14.4 +/- 3.9). The patients reported that the compulsion decreased in intensity and that they were more able to resist the urge to pull out their hair during treatment with clomipramine. We conclude that clomipramine appears to be effective in the short-term treatment of trichotillomania.