Reduced mortality by meeting guideline criteria before using recombinant activated factor VII in severe trauma patients with massive bleeding.

BACKGROUND: Management of trauma patients with severe bleeding has led to criteria before considering use of recombinant activated factor VII (rFVIIa), including haemoglobin >8 g dl-1, serum fibrinogen ≥1.0 g l-1, platelets >50,000 x 109 l-1, arterial pH ≥ 7.20, and body temperature ≥34 °C. We hypothesized that meeting these criteria is associated with improved outcomes. METHODS: In this prospective cohort study of 26 French trauma centres, subjects were included if they received rFVIIa for persistent massive bleeding despite appropriate care after severe blunt and/or penetrating trauma. RESULTS: After surgery and/or embolization as haemostatic interventions, 112 subjects received a first dose of 103 µg kg-1 rFVIIa (82-200) (median, 25th-75th percentile) at 420 min (285-647) post-trauma. Of these, 71 (63%) "responders" were still alive at 24h post-trauma and had their transfusion requirements reduced by > 2 packed red blood cell units after rFVIIa treatment. Mortality was 54% on day 30 post-trauma. There were 21%, 44% and 35% subjects who fulfilled 0-1, 2-3 or 4-5, respectively, of the guidelines before receiving rFVIIa. Survival at day 30 was 13%, 49% and 64% and the proportion of responders was 39%, 64% and 82%, when subjects fulfilled 0-1, 2-3 or 4-5 conditions, respectively (both P <0.01). CONCLUSIONS: In actively bleeding trauma patients, meeting guideline criteria before considering rFVIIa was associated with lower mortality and a higher proportion of responders to the rFVIIa.

Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects.

Population-based association studies have identified several polymorphic variants in genes encoding ion channel subunits associated with the electrocardiographic heart-rate-corrected QT (QTc) length in healthy populations of Caucasian origin (KCNH2 rs1,805,123 (K897 T) and rs3,815,459, SCN5A rs1,805,126 (D1,819D), 1,141-3 C>A, rs1,805,124 (H558R), and IVS24+116 G>A, KCNQ1 rs757,092, KCNE1 IVS2-128 G>A and rs1,805,127 (G38S), and KCNE2 rs2,234,916 (T8A)). However, few of these results have been replicated in independent populations. We tested the association of SNPs KCNQ1 rs757,092, KCNH2 rs3,815,459, SCN5A IVS24+116 G>A, KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 with QTc length in two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2,008 healthy subjects. All polymorphisms were in Hardy-Weinberg equilibrium in both groups. The minor allele SCN5A IVS24+116 A was more frequent in the group of subjects with the shortest QTc, whereas the minor alleles KCNQ1 rs757,092 G and KCNH2 rs3,815,459 A were more frequent in the group with the longest QTc. There was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 between the two groups. Haplotype analysis showed a twofold increased risk of QTc lengthening for carriers of the haplotype, combining alleles C and A of the two common KCNE1 SNPs, IVS2-129 C>T (rs2,236,609) and rs1,805,127 (G38S), respectively. In conclusion, our study confirms the reported associations between QTc length and KCNQ1 rs757,092 and KCNH2 rs3,815,459.

[Neonatal forms of congenital long QT syndrome]. / Formes néonatales du syndrome de QT long congénital.

UNLABELLED: The neonatal congenital long QT syndrome (LQTS) is rare and of bad prognosis due to the presence of severe ventricular arrhythmia and conduction abnormalities. METHODS: we included 24 propositus newborns from our population with LQTS. Genetic study was possible in 19 cases. RESULTS: the diagnosis of LQTS was made according to a QT prolongation associated with a sinusal neonatal bradycardia (n=9) or a 2/1 AV block (n=15). The onset presentation consisted of syncope (n=2), torsades de pointes (n=7), cardiovascular collapse (n=5), cardiac arrest (n=1). The mean QTc was at 550+60 ms. During the neonatal period the treatment consisted of beta-blocking agents in all cases, associated with a definitive pacemaker implantation in 10 cases with 2/1 AV block. Three newborns with a 2/1 AV block died during the first month of life (one case due to a septecemia after implantation of a pacemaker, and two who were waiting for that implantation). All survivors remained asymptomatic during a follow-up period of 7 years. In all cases with a 2/1 AV block we identified mutations in HERG (n=8). Newborns with isolated sinusal bradycardia presented all a mutation in KCNQ1 (n=9). CONCLUSION: the LTQS with 2/1 AV block is preferably associated with mutation in HERO with a bad initial prognosis.

[Homozygotous mutation of the SCN5A gene responsible for congenital long QT syndrome with 2/1 atrioventricular block]. / Mutation homozygote dans le gène SCN5A responsable d'un syndrome de QT long congénital avec bloc auriculo-ventriculaire 2/1.

Long QT syndrome is characterized by a prolongation of the QT interval on the surface ECG. This clinically and genetically heterogeneous cardiac disease is potentially lethal due to ventricular polymorphic tachyarrhythmias leading to syncope or sudden death. It is transmitted according to different mendelian modes due to mutations in several genes coding for cardiac ion channels. Heterozygous mutations in KCNQ1, HERG, SCN5A, KCNE1 and KCNE2 genes are responsible for the dominant form without deafness whereas homozygous mutations in KCNQ1 and KCNE1 are responsible for the recessive form (Jervell and Lange-Nielsen syndrome) associated with congenital deafness. We report the case of a 5 year-old boy referred for syncope with a prolongation of the QTc interval (526 ms) and a 2/1 Atrio-Ventricular (AVB) block on the surface ECG. Under beta-blocking therapy, the sinus rate decreased and the 2/1 AVB disappeared. Electrophysiological study evidenced an infra-hisian block and a unipolar ventricular endocardial pacemaker was implanted. A V1777M missense mutation was identified in the C-terminal part of SCN5A, cardiac sodium channel gene, at the homozygous state in the proband and at the heterozygous state in both parents and 2 sibblings. Only the proband had a severe phenotype with syncope and AV conduction anomalies. All other genetically affected subjects were asymptomatic. This study provides evidence for the involvement of homozygous LQT3 forms in "functional" AVB.

[T wave abnormalities on Holter monitoring of congenital long QT syndrome: phenotypic marker of a mutation of LQT2 (HERG)]. / Anomalies de l'onde T au Holter dans le syndrome du QT long congénital: marqueur phénotypique d'une mutation dans LQT2 (HERG).

The two genes which code for the potassium channels, KCNQ1 and HERG, are responsible for the most common forms of the long QT syndrome, LQT1 and LQT2. Abnormalities of duration and morphology of the ventricular repolarisation are amongst the diagnostic criteria of this syndrome. The morphology of the T waves was studied by 24 hour Holter monitoring in 190 subjects with a long QT syndrome due to KCNQ1 (LQT1) [N = 133] or HERG (N = 57) and in 100 controls, and it was compared with the ECG T wave. The T wave was characterised according to 3 morphological features: grade 0 (G0) = normal, grade 1 (G&) = slight ST depression and grade 2 (G2) = presence of ST elevation of the descending phase of the T wave. The T wave morphology on Holter ECG was normal for most LQT1 and control subjects compared with LQT2 (92%, 96% and 19% respectively, p < 0.01). Grade 1 appearances were observed more often in LQT2 (18 vs 8% for LQT1 and 4% for controls, p < 0.01). Grade 2 appearances were only observed in the cases of LQT2 (63%). The predictive factors of G2 were young age and an anti-sense mutation of the transmembrane domaines of HERG. The authors conclude that Holter monitoring improves detection of T wave changes compared with the ECG. Grade 2 changes seem to be a phenotype marker for a HERG mutation, especially those situated in the transmembrane domaines.

Homozygous SCN5A mutation in long-QT syndrome with functional two-to-one atrioventricular block.

Heterozygous mutations in genes encoding cardiac ionic channel subunits KCNQ1, HERG, SCN5A, KCNE1, and KCNE2 are causally involved in the dominant form of long-QT syndrome (LQTS) while homozygous mutations in KCNQ1 and KCNE1 cause LQTS with or without congenital deafness. In addition, two homozygous HERG mutations have been associated with severe LQTS with functional atrioventricular conduction anomalies in young children. A 2:1 atrioventricular block (AVB) with a major QTc prolongation (526 ms) was evidenced in a 5-year-old boy referred for syncope and seizure. LQTS was diagnosed and beta-blocking therapy initiated leading to normal atrioventricular conduction. Electrophysiological study provided support that location of the AVB was infra-Hisian. DNA analysis was performed in the proband and in asymptomatic family members. A novel missense mutation, V1777M, in the early C-terminal domain of SCN5A was identified. The proband was homozygous while the parents and two siblings were heterozygous carriers. Homozygote and heterozygote expression of the mutant channels in tsA201 mammalian cells resulted in a persistent inward sodium current of 3.96+/-0.83% and 1.49+/-0.47% at -30 mV, respectively, which was dramatically reduced in the presence of tetrodotoxin. This study provides the first evidence for a homozygous missense mutation in SCN5A and suggests that LQTS with functional 2:1 AVB in young children, a severe phenotype associated with bad prognosis, may be caused by homozygous or heterozygous compound mutations not only in HERG but also in SCN5A. The full text of this article is available at http://www.circresaha.org.

Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations.

BACKGROUND: The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients. METHODS AND RESULTS: The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P:<0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P:<0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG. CONCLUSIONS: This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.

Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

UNLABELLED: Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct human hereditary cardiac diseases known to cause ventricular tachyarrhythmias (torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death. OBJECTIVE: In this study we have identified and electrophysiologically characterized, in patients having either LQTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene). METHOD: The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique. RESULTS: The R1512W mutation found in our first patient diagnosed with Brugada syndrome produced a slowing of both inactivation and recovery from inactivation. The R4132G mutation found in our second patient who also presented Brugada syndrome, resulted in no measurable sodium currents. Both Brugada syndrome patients showed ST segment elevation and right bundle-branch block, and had experienced syncopes. The E1784K mutation found in the LQTS showed a persistent inward sodium current, a hyperpolarized shift of the steady-sate inactivation and a faster recovery from inactivation. CONCLUSION: The different clinical manifestations of these three mutations most probably originate from the distinct electrophysiological abnormalities of the mutant cardiac sodium channels reported in this study.

[Congenital long QT syndrome. The value of genetics in prognostic evaluation]. / Syndrome du QT long congénital. Apport de la génétique dans l'évaluation pronostique.

The congenital long QT syndrome (QTL) is a heterogenic clinical and genetic entity characterised by prolongation of the QT interval which may be complicated by syncope and sudden death. Four genes have been identified for the cardiac potassium (KCNQ1, HERG and KCNE1) and sodium (SCN5A). The aim of this study was to assess the prognosis of the disease by the site of mutation identified on the morbid gene. Thirty-two genotyped families participated to this study. Each subject gave a clinical history, an ECG and a search for genetic mutation. Eighteen mutations in the transmembrane domains of KCNQ1 were identified in 25 families and 2 mutations in the C-terminal part were found in 4 families. The phenotype was less severe in C-terminal part mutations: less syncopes and sudden deaths (22 vs 55%, p < 0.001) and a shorter QTc (458 +/- 31 ms vs 479 +/- 31 ms, p = 0.0003). Three mutations were detected in the C-terminal part of HERG in 3 different families. Their phenotype was less severe with syncoped related to hypokalemia. The authors also report the case of a family in which two subjects who were the most severely affected had two mutations, one in HERG and the other in KCNQ1. This study confirms the value of a genetic research in assessing the severity of the congenital long QT syndrome.

C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.

BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in which 4 genes encoding ion-channel subunits have been identified. Most of the mutations have been determined in the transmembrane domains of the cardiac potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3' part of HERG for mutations. METHODS AND RESULTS: New specific primers allowed the amplification of the 3' part of HERG, the identification of 2 missense mutations, S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp insertion, 3108+1G. Hypokalemia was a triggering factor for torsade de pointes in 2 of the probands of these families. Lastly, in a large family, a maternally inherited G to A transition was found in the splicing donor consensus site of HERG, 2592+1G-A, and a paternally inherited mutation, A341E, was identified in KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The discovery of mutations in the C-terminal part of HERG emphasizes that this region plays a significant role in cardiac repolarization. Clinical data suggests that these mutations may be less malignant than mutations occurring in the pore region, but they can become clinically significant in cases of hypokalemia. The first description of 2 patients with double heterozygosity associated with a dramatic malignant phenotype implies that genetic analysis of severely affected young patients should include an investigation for >1 mutation in the LQT genes.

KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome.

BACKGROUND: KVLQT1, the gene encoding the alpha-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhythmias leading to recurrent syncopes and sudden death. However, there is considerable variability in the clinical presentation, and potential severity is often difficult to evaluate. To analyze the relationship between phenotypes and underlying defects in KVLQT1, we investigated mutations in this gene in 20 RWS families originating from France. METHODS AND RESULTS: By PCR-SSCP analysis, 16 missense mutations were identified in KVLQT1, 11 of them being novel. Fifteen mutations, localized in the transmembrane domains S2-S3, S4-S5, P, and S6, were associated with a high percentage of symptomatic carriers (55 of 95, or 58%) and sudden deaths (23 of 95, or 24%). In contrast, a missense mutation, Arg555Cys, identified in the C-terminal domain in 3 families, was associated with a significantly less pronounced QT prolongation (459+/-33 ms, n=41, versus 480+/-32 ms, n=70, P=.0012), and significantly lower percentages of symptomatic carriers (7 of 44, or 16%, P<.001) and sudden deaths (2 of 44, or 5%, P<.01). Most of the cardiac events occurring in these 3 families were triggered by drugs known to affect ventricular repolarization. CONCLUSIONS: Our data show a wide KVLQT1 allelic heterogeneity among 20 families in which KVLQT1 causes RWS. We describe the first missense mutation in the C-terminal domain of KVLQT1, which is clearly associated with a fruste phenotype, which could be a favoring factor of acquired LQT syndrome.

Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome.

The KCNE1 gene encodes a small protein, IsK, of 14.4 kDa, with a single transmembrane domain, and is part of a potassium channel expressed in the heart. This channel is thought to underly the very slow component of the cardiac delayed rectifying current which controls the duration and the degree of ventricular repolarization. This suggested that KCNE1 could be the morbid gene responsible for an autosomal recessive cardio-auditory disease, the Jervell and Lange-Nielsen syndrome, characterized by ventricular repolarization abnormalities and recurrent syncopes leading eventually to sudden death associated with a bilateral congenital deafness. By linkage analysis in four consmanguinous families, using microsatellite markers of chromosome 21 as well as KCNE1 intragenic polymorphisms, we excluded KCNE1 as a candidate gene for Jervell and Lange-Nielsen syndrome. In addition, we described a new polymorphism, a G-to-A substitution at position 253, in the KCNE1 coding sequence detectable by SSCP analysis or RFLP.

A mutation in HERG associated with notched T waves in long QT syndrome.

Long QT syndrome (LQT) is a genetically heterogeneous inherited disorder that causes sudden death from cardiac arrhythmia. Four loci have been mapped to chromosomes 3, 4, 7 and 11 and three specific mutated genes for LQT syndrome have been identified. LQT2 results from mutations in the human ether-a-gogo-related gene, HERG, a cardiac potassium channel, whose protein product likely underlies Ikd the rapidly activating delayed rectifier current. By SSCP analysis and direct sequencing, we determined a new missense mutation in the HERG coding sequence, a G to A transition at position 1681 resulting in the substitution of threonine for a highly conserved alanine at codon 561. This mutation, Ala561Thr, in the coding sequence of the fifth membrane-spanning domain (S5) of the HERG protein seems to convey a risk of cardiac events in affected family members. In addition to a prolonged T wave of low amplitude on the surface ECG, a distinctive biphasic T-wave pattern was found in the left precordial leads of all affected subjects with the Ala561Thr mutation regardless of age, gender and beta blocking therapy.

Characterization and localization of an immunoreactive growth hormone-releasing hormone precursor form in normal and tumoral human anterior pituitaries.

Arguments favor an in situ synthesis of GH-releasing hormone (GHRH) in the normal and tumoral human anterior pituitary. These tissues may express human (h) GHRH messenger RNA, contain hGHRH-(1-44)-NH2, and secrete in vitro an immunoreactive form (ir-form) of the peptide. Here, we characterize and localize the precursor of hGHRH in human anterior pituitary tissues using RIAs specific for the C-terminus or the midportion of hGHRH-(1-44)-NH2, size-exclusion chromatography, HPLC, Western blotting, and immunocytochemistry. The anterior pituitary ir-forms were compared to those found in hypothalamus, posterior pituitary, and GHRH-secreting endocrine pancreatic tumors. Three ir-forms of hGHRH with mol wt of 30-45, and 5 kilodaltons (kDa) were detected. The 30- to 45-kDa ir-form was very likely to consist of hGHRH bound to proteins. The 5-kDa ir-form represented mature forms of hGHRH. It was the major form in tissues actively synthesizing and/or secreting hGHRH. Nontumoral anterior pituitaries contained significant amounts of mature hGHRH. The 10-kDa form was identified as a hGHRH precursor ir-form. In addition to its expected presence in the hypothalamus and GHRH-secreting tumors, normal and tumoral human anterior pituitaries contained an identical ir-form of the hGHRH precursor. Cells immunoreactive for the hGHRH precursor were observed in pituitary adenomas. Evidence for precursor and mature ir-forms of hGHRH in anterior pituitary tissues provides conclusive arguments for the endogenous synthesis of the neuropeptide.

Stimulatory effect of gonadotropin-releasing hormone (GnRH) on in vitro prolactin secretion and presence of GnRH specific receptors in a subset of human prolactinomas.

The purpose of this study was to determine whether gonadotropin-releasing hormone (GnRH) may exert a direct action on human prolactinomas. On a series of 17 adenomas, we studied the effect of GnRH on the in vitro prolactin (PRL) secretion of dispersed and perifused cells of 10 cases and the [125I]GnRH agonist binding on frozen sections of three out of the adenomas studied in perifusion and on the membrane preparations of seven other cases. Two 20-min pulses of GnRH (10(-7) mol/l) stimulated the in vitro PRL secretion of three adenomas out of 10 (increase of 200, 444 and 205%, respectively, above basal levels). The GnRH receptors of three adenomas bound GnRH agonist (Des-Gly10-(D-Ala6)-GnRH ethylamide). The binding was specific, with a high affinity (Kd = 0.60, 0.48 and 0.40 nmol/l) similar to that of two human anterior pituitaries obtained post-mortem (Kd = 0.70 and 0.40 nmol/l). Indirect immunoperoxidase revealed that the majority of the cells (60-90%) in all the adenomas studied contained immunoreactive PRL. Four of them also contained cells immunoreactive to the alpha-subunit of the glycoprotein hormones. In none of the prolactinomas were cells immunoreactive to antiserum of anti-beta-luteinizing hormone, anti-beta-follicle-stimulating hormone or anti-beta-thyrotropin. All the prolactinomas that were responsive to GnRH in perifusion experiments and/or bound specifically to [125I]GnRH agonist were also immunoreactive for alpha-subunit. These results show that GnRH, via GnRH specific receptors, exerts a stimulation on in vitro PRL secretion in a subset of prolactinomas characterized by the presence of alpha-subunit.

Effect of the slow-release formulation of somatuline (BIM 23014) on estrogen-induced hyperprolactinemia and lactotroph hyperplasia in the female rat.

Somatuline, in common with other SRIH analogues, exerts antiproliferative and antisecretory activities on various tumors. Our purpose was to test the effectiveness of a slow-release formulation of somatuline on lactotroph hyperplasia and PRL hypersecretion induced by estrogens (17 beta E2) in rats. Female rats were primed with 17 beta E2 for 6 weeks before receiving somatuline (2 mg/kg) intramuscular injections every 10 days for one month. The mean anterior pituitary weight was 11.22 +/- 0.32 mg (mean +/- SEM) in non-estrogenized rats, 29.62 +/- 1.63 mg in 17 beta E2-primed rats and 23.58 +/- 1.26 mg in 17 beta E2-primed somatuline-treated rats. Mean plasma PRL level was 5.63 +/- 0.97 ng/ml, 182.37 +/- 27.55 ng/ml and 113.89 +/- 15.07 ng/ml in the same groups respectively. Thus, the 17 beta E2-induced pituitary enlargement and hyperprolactinemia were 20% and 38% lower respectively when animals were treated with somatuline during the last month of estrogenization. The 17 beta E2-induced increase in PRL cell density was also reduced by somatuline treatment. We conclude that the slow-release formulation of somatuline impedes 17 beta E2-induced hyperprolactinemia and pituitary enlargement concomittantly, at least in part by acting on lactotroph proliferation.

Evidence of gonadotropin-releasing hormone mRNA in the rat anterior pituitary.

We have previously reported the presence and the persistence of immunoreactive GnRH cells in the rat anterior pituitary in the absence of exogenous GnRH. To substantiate the hypothesis of its endogenous production, we have investigated the presence of GnRH mRNA in rat anterior pituitary tissue using a reverse transcription-polymerase chain reaction (RT-PCR) amplification protocol. Total RNA from rat anterior pituitary, hypothalamus (positive control), and muscle (negative control) was reverse transcribed to the first strand of cDNA and amplified by PCR using a set of three exon-specific primers for a target sequence of the GnRH gene, i.e. two external 5' and 3' primers and one internal 3' primer. UV light analysis of the size-fractionated RT-PCR products showed two bands of the predicted sizes [511 and 397 base pairs (bp)] hybridizing with GnRH probes in Southern analysis only in hypothalamus and in anterior pituitary but not in muscle. These two bands were far more intense in the hypothalamus than in the anterior pituitary. Restriction enzyme analysis evidenced that the two RT-PCR products included the HindIII endonuclease site of cleavage present in the GnRH cDNA sequence spanned by the primers, yielding two digested products of the anticipated sizes (86 and 425 bp for the 511-bp fragment, and 86 and 311 bp for the 397-bp fragment). The complementary sequences for the GnRH probes were conserved in the 425-bp and 311-bp fragments. Based on these results, we can conclude that the RT-PCR products generated from RNA tissue were the target GnRH sequences in the anterior pituitary as well as in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin cells in human somatotropic adenomas.

Data from our group have shown that the human adenomatous and normal anterior pituitary may be the source of somatostatin (SRIH). SRIH-producing cells were identified in two somatotropic adenomas. Immunoreactive SRIH cells were present in both cases. In case 2, material was available for RNA studies, in situ hybridization and electron microscopy. The size of the transcript identified by Northern blot analysis was identical to that of hypothalamic SRIH mRNA. In situ hybridization showed that the SRIH gene was expressed in a cell subset superimposable to that identified by immunocytochemistry. Co-localization studies revealed that SRIH and growth hormone (GH) immunoreactivities were not present in the same cells. Ultrastructural immunogold labelling showed that SRIH cells had features distinct from those of the somatotropes. The results confirm that the somatotropic adenomas have the ability to synthesize SRIH, indicate that SRIH expression is restricted to a subset of adenoma cells different from GH-producing cells, and imply that SRIH cells are involved in paracrine regulation of neighbouring somatotropes.

[Note on the detection of hemoglobin lepore in a Senegalaise (author's transl)]. / A propos de la découverte d'une hémoglobine Lepore chez un Senegalais.

After reviewing briefly the characteristic features of hemoglobins Lepore, their distribution and their clinical symptoms, the authors report on a senegalese case.