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.     

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.      

Determination of cycloserine in human plasma by high-performance liquid chromatography with fluorescence detection, using derivatization with p-benzoquinone

A new method for determining cycloserine in plasma samples is described. This method is based on the derivatization of cycloserine with p-benzoquinone, a reaction that takes place at the same time as the process of plasma deproteinization due to the presence of ethanol as solvent in the solution of the derivatization reagent. Four derivatives are obtained from this reaction. The main derivative is well correlated with the cycloserine concentration. The ratio between the volumes of the plasma sample and the reagent solution is 1:2 for a p-benzoquinone concentration of 1000 microg/mL. Elution from a C18 column was isocratic, using a mobile phase containing (v/v) 85% aqueous 0.1% formic acid solution, and 15% (v/v) of a mixture of methanol and acetonitrile (1:1), with a flow-rate of 1 mL/min, at 25 degrees C. Determinations by fluorescence detection were achieved with excitation at 381 nm and emission at 450 nm, with a detection limit of 10 ng/mL for an injection volume of 5 microL. This method was validated and applied to the determination of cycloserine in blood plasma samples of several healthy volunteers.     

Cerebral abscesses in children

Summary The authors analyze 81 cases of cerebral abscess in children admitted to the Clinic of Neurosurgery Bucharest, from 1936 to 1964; these cases represent 15 per cent of the total number of 542 cerebral abscesses treated in the clinic.A progressive increase was found in the incidence of cerebral abscesses during the last 10 years; an increase was also observed with the increase in age-group.Of the 81 cases 49 occurred in boys.In accordance with their origin there were: 56% contiguous cerebral abscesses (46% otogenic, 6% rhinogenic, 4% other causes); 17% were associated with the congenital cyanotic disease; 15% were post-traumatic abscesses and 12% of undetermined origin.The location was supratentorial in 56 cases, infratentorial in 23 cases and supra- and infratentorial in 2 cases. There were 17 frontal locations, 17 temporal locations, 4 parietal, 2 occipital; in 10 cases two lobes were involved, in 4 cases three lobes and in 1 case one of the cerebral hemispheres. There were 23 cerebellar abscesses and in 2 cases the abscess was supra- and infratentorial.The clinical picture was dominated by the syndrome of raised intracranial pressure (80 per cent of the cases); the evolution of almost half of the cases was afebrile.Among the clinical features of cerebral abscesses in children particular stress is laid on cerebral abscess in infants and on abscesses accompanying a congenital cyanotic cardiopathy.The difficulties of differential diagnosis with focal encephalities, cortical thrombophlebitis, otogenic hydrocephalus, cerebral tumour, etc. are discussed.The treatment of cerebral abscesses in children is considered by the authors as a neurosurgical emergency. They recommend total ablation of the abscess as the best method of treatment, because of the favourable, immediate and late results (the formation of a supple cicatrix) it offers. The surgical treatment was associated with antibiotics, antioedematous medication, corticotherapy and anticonvulsants.Of the 75 children operated on 42 recovered and 12 showed improvement. There was no lethal case in the 25 cerebral abscesses operated on during the last 5 years.

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Zusammenfassung Die Autoren geben eine Analyse von 81 Fällen kindlicher Hirnabszesse, die zwischen 1936 und 1964 in der Neurochirurgischen Klinik Bukarest beobachtet wurden. In dieser Zeit wurden insgesamt 542 Hirnabszesse behandelt. Die kindlichen machen davon 15% aus. Die Häufigkeit hat in den letzten Jahren zugenommen. Die Hirnabszesse sind bei älteren Kindern häufiger. Sie kommen bei Knaben häufiger vor als bei Mädchen.56% waren fortgeleitet entstanden (46% otogen, 6% rhinogen, 4% andere Ursachen). 17% traten im Verlauf angeborener Herzmißbildungen mit Zyanose auf. 15% entstanden posttraumatisch. Bei 12% war die Ursache nicht zu klären.56 Fälle lagen supratentoriell, 24% infratentoriell und 2 sowohl supra- als auch infratentoriell. 17 waren frontal, 17 temporal, 4 parietal und 2 okzipital lokalisiert. Bei 10 Fällen waren zwei Hirnlappen, bei 4 Fällen drei und bei 2 Fällen eine ganze Hirnhemisphäre befallen. Bei 23 Fällen fand sich der Abszeß im Kleinhirn.Das klinische Bild wurde von den Zeichen intrakranieller Drucksteigerung (80%) beherrscht. Beinahe 50% der Fälle verliefen afebril.Auf die Besonderheiten des Hirnabszesses bei Säuglingen und bei angeborenen Herzmißbildungen im Rahmen des Morbus Coerulius wurde eingegangen. Die Schwierigkeiten der Diagnose und der differentialdiagnostischen Abgrenzung von Herdenzephalitiden, kortikaler Thrombophlebitis, otogenem Hydrozephalus, Hirntumoren usw. wurden besprochen. Der diagnostische Wert von EEG, Angiographie und Kontrastdarstellung des Abszesses wurde betont.Als Behandlung der Wahl gilt die Totalexstirpation, weil sie die besten Früh- und Spätergebnisse gewährleistet und die resultierende Hirnnarbe weniger derb ist. Zusätzlich wurden Antibiotika, Osmotherapeutika, Kortikoide und Antiepileptika gegeben.Von 75 operierten Kindern genasen 42. Bei 12 weiteren wurde eine Besserung erzielt. In den letzten 5 Jahren wurde bei 25 operierten Kindern kein Todesfall mehr verzeichnet.

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Resumen Los autores presentan el análisis de 81 casos de absceso cerebral en niños, casos que se investigaron en la Clínica de Neurocirurgía de Bucarest entre los años 1936 y 1964 y que representan un 15% del total de los 542 abscesos cerebrales registrados en la clínica.Se comprueba un crecimiento progresivo de la frecuencia de los abscesos cerebrales en los últimos 10 años; se observa tambien que la frecuencia crece paralelamente al aumento de la edad de los niños.Predominan los abscesos cerebrales entre los varones (49 casos).Según su origen se encontraron: 56% abscesos cerebrales subyacentes (46% otógenos, 6% rinógenos, 4% debidos a otras causas); 17% abscesos asociados a la enfermedad cianógena congénita; 15% abscesos post-traumáticos y 12% abscesos de origen indeterminado.Desde el punto de vista de su localización, hubo 56 casos supratentoriales, 23 casos infratentoriales y 2 casos supra e infratentoriales. Con localización frontal hubo 17 casos, temporal 17 casos, parietal 4 casos y occipital 2 casos; en 10 casos, el absceso afectó 2 lóbulos, en 4 casos 3 lóbulos y en 2 casos un hemisferio cerebral. 23 abscesos fueron cerebelosos y 2 situados encima y debajo del tentorio.El síndrome de hipertensión intracraneana predominó en el cuadro clínico (80% de los casos); y casi la mitad de los casos evolucionaron sin fiebre.Entre las peculiaridades clínicas del absceso cerebral infantil se ponen de relieve los abscesos cerebrales entre los niños de pecho y los que se asocian a una cardiopatia cianógena congénita.Se discuten las dificultades que encuentra el diagnóstico del absceso infantil en comparación con la encefalitis en el foco, la tromboflebitis cortical, la hidrocefalia otógena, el tumor cerebral, etcétera.Los exámenes paraclínicos subrayan el valor de la electroencefalografia, de la arteriografia cerebral y de la abscesografia.El tratamiento de los abscesos infantiles impone, según los autores, la urgencia neuroquirúrgica; basados en su experiencia, ellos recomiendan como método exclusivo de tratamiento la ablación total del absceso, por dar este método los resultados más favorables tanto inmediatos como ulteriores (permitiendo la formación de una cicatriz cerebral más blanda. El tratamiento quirúrgico se asoció a una medicación antibiótica, antiedematosa, a la corticoterapia y al empleo de anticonvulsivos.De los 74 niños operados sanaron 42 y mejoraron 12. En los últimos 5 años, entre los 25 abscesos cerebrales infantiles operados, no se registró ningún caso de fallecimiento.

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Résumé Les auteurs présentent l'analyse clinique de 81 cas d'abcès cérébraux chez l'enfant, opérés dans la Clinique Neurochirurgicale de Bucarest (Roumanie), depuis 1936 jusqu'à 1964. Ces cas représentent 15% du nombre total de 542 abcès cérébraux hospitalisés dans cette période.On a pu constater, surtout dans les deux dernières années, une fréquence plus grande aussi bien qu'un accroissement du nombre des cas par rapport aux groupes d'âge des enfants.Le nombre de cas chez les garçons (49) l'a emporté sur ceux de l'autre sexe. La répartition des cas d'après leur origine fut la suivante: abcès de voisinage: 56% (dont 46% otogènes, 6% rhinogènes et 4% d'origine différente); abcès associes à une maladie cyanogène congénitale: 17%; abcès posttraumatiques: 15%; abcès d'origine indéterminée: 12%.La répartition des cas d'après la localisation: 56 cas furent des abcès supratentoriels, 23 cas soustentoriels et 2 cas mixtes. Parmi les 56 cas à localisation supratentorielle 17 étaient dans le lobe frontal; 17 dans le lobe temporal, 4 dans le lobe pariétal et 2 dans le lobe occipital; dans 10 cas l'abcès s'étendait à deux lobes, dans 4 cas à trois lobes et dans 2 cas l'abcès envahissait tout un hemisphère cérébral.Un syndrome d'hypertension intracranienne dominait l'aspect clinique dans 80% des cas et environ la moitié des cas eurent une évolution afébrile.Les auteurs insistent sur les particularités cliniques des abcès cérébraux chez le nourrisson et sur ceux accompagnant une cardiopathie cyanogène congénitale.On discute les difficultés diagnostiques de l'abcès cérébral chez les enfants surtout avec l'encéphalite en foyer, avec la trombophlébite corticale, l'hydrocéphalie otogène et les tumeurs cérébrales.Parmi les investigations paracliniques, on souligne la valeur de l'electroencéphalogramme, de l'angiographie cérébrale et de l'abcessographie.Les auteurs insistent sur le caractère d'urgence neurochirurgicale et, de par leur expérience, sont d'avis que le seul traitement qui puisse assurer les meilleurs résultats aussi bien immédiats que tardifs (cicatrice cérébrale plus souple) est l'ablation totale de l'abcès.Une médication antibiotique et antioedémateuse aussi bien qu'une corticotherapie et, des anticonvulsivants ont été constamment associées au traitement chirurgical.Du nombre de 75 enfants opérés, 42 ont été complètement guéris et 12 ameliorés. Dans les derniers 5 ans, il n'y eut aucun decès parmi les 25 enfants opérés pour abcès cérébral.

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Riassunto Gli AA. fanno l'analisi clinica di 81 casi di ascessi cerebrali nei bambini, osservati nella Clinica Neurochirurgica di Bucarest, dal 1936 al 1964, e scelti tra 542 casi di ascessi osservati nello stesso periodo.Si nota un accrescimento notevole della casistica negli ultimi 10 anni e con l'età del malato; il sesso maschile è stato molto più frequentemente colpito (49 casi).Dal punto di vista dell'eziologia sono stati riscontrati: 56% di ascessi per contiguità, tra cui: 46% ascessi otitici, 6% ascessi rinogeni e 4% da altre cause; 17% associati a cardiopatie cianogene congenite, 15% ascessi post-traumatici e 12% ascessi d'origine sconosciuta.La sede degli ascessi è stata molto variabile: 56 ascessi erano sopratentoriali, 23 ascessi sottotentoriali e 2 sopra- e sottotentoriali insieme. Tra gli ascessi sopratentoriali sono stati osservati: 17 casi in sede frontale, 17 in sede temporale, 4 in sede parietale e 2 in sede occipitale. In 20 altri casi risultavano lesi 2 lobi cerebrali, in quattro 3 lobi ed in un caso un emisfero intero.In quadro clinico era dominato dclla sindrome di ipertensione endocranica (80% dei casi); il 50% dei malati era apirettico.Tra le forme cliniche dell'ascesso cerebrale nei bambini, si mettono in rilievo quello del neonato e quello associato alla cardiopatia cianogena congenita.Vengono indicate inoltre brevemente le difficoltà di una diagnosi differenziale tra encefalite a focolaio, tromboflebite corticale, l'idrocefalia otitica ed i tumori cerebrali. Tra le indagini paracliniche si sottolinea l'importanza dell'elettroencefalografia, dell'angiografia cerebrale e dell'ascessografia con aria.La terapia degli ascessi cerebrali nei bambini costituiscono, secondo gli AA., una necessità neurochirurgica urgente e, come tale, il metodo chirurgico di elezione è l'asportazione totale dell'ascesso, visto che i risultati, tanto immediati quanto a distanza, sono migliori dopo l'operazione: per es. si ha una gliosi cerebrale meno retrattile e quindi una minore frequenza dell'epilessia.Alla cura chirurgica si è associato la terapia antibiotica, la medicazione dell'edema cerebrale, i cortisonici ed i farmaci anticonvulsivi.Tra i 75 casi operati si notano: 42 guarigioni e 12 miglioramenti clinici. Negli ultimi 5 anni non si deplora nessun caso mortale nei 25 ascessi cerebrali operati.

     

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.     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。