Evolutionary history of the Afro-Madagascan Ixora species (Rubiaceae): species diversification and distribution of key morphological traits inferred from dated molecular phylogenetic trees.

BACKGROUND AND AIMS: Previous work on the pantropical genus Ixora has revealed an Afro-Madagascan clade, but as yet no study has focused in detail on the evolutionary history and morphological trends in this group. Here the evolutionary history of Afro-Madagascan Ixora spp. (a clade of approx. 80 taxa) is investigated and the phylogenetic trees compared with several key morphological traits in taxa occurring in Madagascar. METHODS: Phylogenetic relationships of Afro-Madagascan Ixora are assessed using sequence data from four plastid regions (petD, rps16, rpoB-trnC and trnL-trnF) and nuclear ribosomal external transcribed spacer (ETS) and internal transcribed spacer (ITS) regions. The phylogenetic distribution of key morphological characters is assessed. Bayesian inference (implemented in BEAST) is used to estimate the temporal origin of Ixora based on fossil evidence. KEY RESULTS: Two separate lineages of Madagascan taxa are recovered, one of which is nested in a group of East African taxa. Divergence in Ixora is estimated to have commenced during the mid Miocene, with extensive cladogenesis occurring in the Afro-Madagascan clade during the Pliocene onwards. CONCLUSIONS: Both lineages of Madagascan Ixora exhibit morphological innovations that are rare throughout the rest of the genus, including a trend towards pauciflorous inflorescences and a trend towards extreme corolla tube length, suggesting that the same ecological and selective pressures are acting upon taxa from both Madagascan lineages. Novel ecological opportunities resulting from climate-induced habitat fragmentation and corolla tube length diversification are likely to have facilitated species radiation on Madagascar.

Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the entorhinal cortex exerts a main inhibitory effect on the olfactory input via the amygdala basolateral nucleus and to a lesser extent the piriform cortex. The potential role of these effects on the processing of olfactory information is discussed.

Evidence for the Involvement of Rat Olfactory Bulb in Processes Supporting Long-Term Olfactory Memory.

Current advances in the neurobiology of learning and memory suggest the existence of experience-induced plasticity in sensorial pathways conveying relevant information to higher integrative brain structures. For instance, olfactory learning is known to induce long-lasting modifications of neural activity at the level of the first relay structure of the olfactory system, the olfactory bulb. The observed forms of plasticity depend on the action exerted during learning by ascending neuromodulatory systems, such as the noradrenergic (NA) system originating from the locus ceruleus. This study was aimed at investigating the importance of olfactory bulb plasticity in learning and retention of an olfactory task. In a daily training schedule animals had to learn to use multi-site electrical stimulation patterns of the olfactory bulb as discriminative cues for choosing between a palatable and a nonpalatable solution. We first examined the effects of a continuous intrabulbar infusion of propranolol (a beta-NA receptor antagonist) carried out during the learning period. We found that this treatment neither impaired the retention of a previously learned task nor the learning of a new task. However, the animals presented a severe deficit in long-term retention (>5 days) of the task learned under perfusion. Unexpectedly, this effect cannot be ascribed to a selective blockade of beta-NA receptors since infusion of the drug vehicle (saline-ascorbate) produced exactly the same deficit while a saline solution remained without effect. A final experiment showed that the selective deficit in long-term retention was not observed when the infusion of the saline-ascorbate solution started on the day following completion of learning. Taken together, these results suggest that ascorbate-sensitive neural processes occurring within the olfactory bulb during learning are of functional importance for long-term storage of olfactory information.

Olfactory learning induces differential long-lasting changes in rat central olfactory pathways.

In the present work, we investigated lasting changes induced by olfactory learning at different levels of the olfactory pathways. For this, evoked field potentials induced by electrical stimulation of the olfactory bulb were recorded simultaneously in the anterior piriform cortex, the posterior piriform cortex, the lateral entorhinal cortex and the dentate gyrus. The amplitude of the evoked field potential's main component was measured in each site before, immediately after, and 20 days after completion of associative learning. Evoked field potential recordings were carried out under two experimental conditions in the same animals: awake and anesthetized. In the learning task, rats were trained to associate electrical stimulation of one olfactory bulb electrode with the delivery of sucrose (positive reward), and stimulation of a second olfactory bulb electrode with the delivery of quinine (negative reward). In this way, stimulation of the same olfactory bulb electrodes used for inducing field potentials served as a discriminative cue in the learning paradigm. The data showed that positively reinforced learning resulted in a lasting increase in evoked field potential amplitude restricted to posterior piriform cortex and lateral entorhinal cortex. In contrast, negatively reinforced learning was mainly accompanied by a decrease in evoked field potential amplitude in the dentate gyrus. Moreover, the expression of these learning-related changes occurred to be modulated by the animals arousal state. Indeed, the comparison between anesthetized versus awake animals showed that although globally similar, the changes were expressed earlier with respect to learning, under anesthesia than in the awake state. From these data we suggest that associative olfactory learning involves different neural circuits depending on the acquired value of the stimulus. Furthermore, they show the existence of a functional dissociation between anterior and posterior piriform cortex in mnesic processes, and stress the importance of the animal's arousal state on the expression of learning-induced plasticity.

Involvement of the olfactory bulb in consolidation processes associated with long-term memory in rats.

In a daily training paradigm, rats were trained to discriminate between spatially distinct electrical stimulations delivered to one olfactory bulb. Xylocaine injections were used to disrupt the olfactory bulb functioning in the region close to the electrode tips for 1 hr after training session. The treatment started either just after the session or 2 hr later. When compared with the performance of saline-injected rats, the performance of Xylocaine-injected rats was unimpaired except when the treatment started just after the daily session. In that case, acquisition of the task was slightly altered, and retention over a 5-day period was dramatically impaired. We therefore concluded that, within about 1 hr following training, the olfactory bulb is engaged in consolidation processes critical for long-term retention of learned olfactory cues.

Perceptive properties of the multi-site electrical microstimulation of the olfactory bulb in the rat.

Electrical microstimulation of the olfactory bulb in different locations has been shown to provide water-deprived rats with discriminative cues for selecting a palatable solution without tasting it in a two-choice test. Some perceptive properties of bulbar electrical stimulation were investigated. It was shown that the perceptive effect evoked by stimulating a given site could be recognized when this site was stimulated together with several others. The animals' perception of multi-site stimulation patterns seems therefore to be analytical rather than synthetic. Discrimination of stimulation patterns did not require presentation of concurrent patterns inside a short time interval. Identification of a multi-site pattern was possible when this pattern was presented alone in a test session. Individual characteristics of bulbar microstimulation appear to be perceived absolutely rather than differentially. A good retention of the discrimination learning of specific stimulation patterns was observed. Animals could identify stimulation patterns after complete interruption of the training for 17 days. The results are discussed with reference to the properties of the natural stimulation of the olfactory system.

On the ability of rats to discriminate between microstimulations of the olfactory bulb in different locations.

An investigation was made into the ability of rats to discriminate between electrical stimulations applied to the mitral cell layer of the olfactory bulb in different locations. Water-deprived rats implanted with permanent electrodes were trained to use single- or multi-site microstimulations as discriminative stimuli for selecting a palatable solution without tasting it in a two-choice test. Spontaneous reactions of the animals to stimulation with sinusoidal currents higher than 3 microA per electrode resembled sensory arousal. All rats were found to discriminate between the effects of concurrent microstimulations applied to bulbar sites separated by 500 micron. Changing the current intensity in the range 4-20 microA had no detectable effect on the discrimination. Discrimination was still possible, with a few exceptions, when electrodes were separated by 250 micron and even when they were closely adjacent. Spatial resolution of discrimination seemed not to vary in different regions along the rostrocaudal axis of the bulb. The discrimination of patterns of simultaneous stimulation at several sites was also investigated. Different multi-site patterns were easily distinguished, even when their respective components were closely adjacent or when some components occupied the same area. The findings are discussed with reference to the concept of spatial coding of odours in the olfactory bulb.

An investigation of some temporal aspects of olfactory coding with the model of multi-site electrical stimulation of the olfactory bulb in the rat.

Electrical stimulation of the olfactory bulb was used to investigate some temporal aspects of olfactory coding, with reference to respiration. Food-deprived rats implanted with permanent electrodes were trained to use bulbar multi-site stimulation patterns as discriminative stimuli for predicting the nature of an incoming reinforcement. Electrical pulse trains (100 Hz) were periodically delivered in phase with precisely defined moments of the respiratory cycle (during inspiration or expiration). Temporal aspects of olfactory coding were first considered through the measurement of the minimum duration of a stimulus necessary to identify this stimulus. The results showed that a bulbar stimulation lasting for 30 ms (3 pulses), and delivered during inspiration, was clearly identified by the rats. Stimulus identification induced a discriminative respiratory response which could manifest itself as early as the first cycle concomitant with the beginning of stimulation. It was then shown that a bulbar electrical stimulation pattern was identified with the same latency whether it occurred during expiration or during inspiration. Moreover, the perceptive events induced in those two conditions of stimulation were not different enough to be discriminated by the animals. The findings are discussed within the framework of olfactory information processing.

A study of the effects of noradrenaline in the rat olfactory bulb using evoked field potential response.

In the rat, the main olfactory bulb receives a strong noradrenergic (NA) input from the locus coeruleus which is critical for different types of olfactory learning. However, the resulting effect of NA modulation on on the olfactory bulb electrical activity and its pharmacology are not well understood. In this study, we investigated the action of NA on the bulbar neuronal population using evoked field potentials (EFP) elicited antidromically in the olfactory bulb of anesthetized rats, by stimulation of the lateral olfactory tract (LOT). EFPs in response to single and paired-pulse stimulation of the LOT were collected before, during and until 2 h after a 10 min perfusion of pharmacological agents through a push-pull cannula. Four concentrations of NA were tested ranging from 10(-5) M to 10(-2) M. NA induced a reversible dose-dependent effect. The major effect was observed at 10(-3) M. It consisted of an increase in Component 2 amplitude (depolarization of granules cell dendrites) and a decrease in Component 3 amplitude (depolarization of granule cell bodies). In parallel, paired-pulse inhibition of mitral cells by granule cells was increased. The alpha 1 agonist phenylephrine (10(-3) M) mimicked most of the effects of NA whereas the alpha 1 antagonist prazosin (10(-3) M) blocked its main action. Isoproterenol (beta agonist, 10(-3) M) and clonidine (alpha 2 agonist, 10(-3) M) could not reproduce the effects of NA. Thus mainly through the activation of alpha 1 receptors, NA enhances synaptic activation of granule cells and increases feed-back inhibition of mitral cells. Consequences of such effects in the context of learning and memory are discussed.

Behçet's syndrome and factor XII deficiency.

Several mechanisms have been proposed to explain thrombotic tendency in Behçet's syndrome. We report the case of a 43-year old woman presenting retinal-vein thrombosis, factor XII deficiency and Behçet's syndrome. This kind of association has thus far never been reported. Factor XII deficiency is known to possibly induce various types of thrombosis and might explain the prevalence of ocular symptoms in our patient.

Circulatory assist techniques after cardiomyoplasty. Determinants for clinical outcome and later consequences.

Cardiomyoplasty, in spite of recent improvements, remains a high risk operation. The early postoperative period is sometimes very critical, even for patients selected from preoperative New York Heart Association functional class IV. During the surgical period, poor hemodynamics may be responsible for early death, as well as influence latissimus dorsi muscle long-term viability. Circulatory assist, including pharmacologic support with enoximone, intraaortic balloon counterpulsation (IABP), and ventricular assist devices (VAD), may be needed. From February, 1993 to September, 1994, 14 clinical dynamic cardiomyoplasty procedures were performed using the Medtronic (Minneapolis, MN) system at Hôpital La Timone, Marseille, France. Eight patients suffered from early and severe postoperative heart failure. Enoximone was used in three patients and IABP in five patients. Two days after cardiomyoplasty, one of the IABP patients required an implantable left VAD (Thermocardio Systems, Woburn, MA) as a bridge to cardiac transplantation. Overall hospital mortality was 7%. The authors studied the preoperative clinical data and surgical techniques to find specific risk factors that could have influenced postoperative events. Another aim of this study was to evaluate long-term benefits in these particular patients. Results showed that cardiomyoplasty patients may require complex means to overcome postoperative hemodynamic failure, but without necessarily poor long-term results. This should be an important step in improving future patient selection.

[Percutaneous transluminal valvuloplasty in pulmonary stenosis. Apropos of 24 cases]. / Valvuloplastie transluminale percutanée des sténoses pulmonaires. A propos de 24 cas.

Twenty-four patients with moderate or severe valvular pulmonary stenosis were treated by percutaneous transluminal valvuloplasty (PTV). The age of the patients ranged from 24 hours to 27 years. Eighteen patients (group I) had a right ventricle-pulmonary artery (RV-PA) pressure gradient greater than 50 mmHg (measured simultaneously or during catheter withdrawal). Six patients (group II) had RV-PA pre-sure gradients of less than 50 mmHg. Twenty-seven PTV procedures were performed. Six of the 24 patients were under 2 months of age, including 4 who were less than 1 week old. The youngest patient (under 24 hours old) had valvular pulmonary stenosis, very nearly atresia. PTV was carried out using Rashkind's technique on 2 occasions and with a dilatation catheter with a balloon of 6 to 20 mm of diameter on the other 25 occasions. In 6 cases, 2 dilatation catheters were introduced and inflated simultaneously in the pulmonary valve. The overall results were satisfactory: RV pressure fell from 87.6 to 54.4 mmHg, the RV-PA gradient from 72.3 to 31.9 mmHg and the ratio of RV/systemic pressure from 104.4 to 51.1. The improvement was more marked in group I than in group II. The causes of failure are discussed: valvular dysplasia, severe infundibular hypertrophy, inadequate diameter of the balloon. Tolerance of PTV was very good. The value of this procedure is emphasised. It may save surgical valvotomy in high risk groups of patients, such as the newborn and infants. The haemodynamic results of PTV are maintained at long-term, but the number of cases is still too small.

[Mitral valve replacement with bioprosthesis in children]. / Remplacement valvulaire mitral par bioprothèse chez l'enfant.

Forty seven bioprostheses were used for mitral valve replacement between January 1975 and June 1980, with no operative mortality, in children under 19 years of age. This study was undertaken to evaluate the medium and longterm outcome of 43 patients followed up for at least 2 years. The late mortality was higher in children under 13 years of age (11.1% per patient/year) than in older children (3% per patient/year). The incidence of reoperation for deterioration of the bioprosthesis was 5,5% per patient/year. The actuarial longevity of bioprostheses without any complications was 48 +/- 16% at 5 years. After a review of the literature, the authors discuss their present therapeutic attitude: whenever possible, mitral valvuloplasty is the operation of choice, but when valve replacement is necessary, two criteria must be considered: the age of the patient and conditions of follow up. If medical follow-up facilities are good: mechanical prostheses are preferred in patients under 13 years of age: after puberty especially in girls, the bioprosthesis is the valve of choice. If medical follow-up facilities are poor: the valve of choice is a bioprosthesis at all ages because of the risk of thromboembolism and the relatively slow clinical aggravation in cases of bioprosthetic deterioration.

[Repeated heart valve replacements: prognosis and results]. / Remplacements valvulaires itératifs; pronostic et résultats.

In order to determine the prognosis of reoperation for valvular replacement, we reviewed the results of a consecutive series of 124 patients operated in the department between 1974 and 1992 (163 multi redo operations). There were 69 women and 55 men, with a mean age 48 years; 77% of the patients were in functional class III or IV. Operations were performed as an emergency in 30% of cases. Endocarditis was found in 24% of cases and was an important risk factor in this content. The main indications for reoperation were periprosthetic leakage in 28.8% of cases and failure of bioprostheses in 23.7%. The valvular replacement was simple in 61%, double in 32% and triple in 7% of cases. An associated procedure was necessary in 27% of cases. Mechanical devices were implanted in 62.3% of cases. Peroperative mortality was 3% and hospital mortality, mainly from cardiac causes, was 21.7% for the second, 20% for the third and 55.6% for the fourth reoperations. Operative mortality was dependent on the number or reoperations, functional class, emergency surgery, duration of bypass and cross-clamping time. Four per cent of patients were lost to follow-up and 30 patients died secondarily. The actuarial survival rate was 52% at 5 years and 33% at 10 years, actuarial survival rate without valvular complication was 41% at 5 years and 19% at 10 years but the functional results remained good with over 90% of patients in functional class I or II at the end of follow-up.

[18 and one-half years' survival after cardiac graft. Clinical course and anatomical findings]. / Survie de 18 ans et demi après greffe cardiaque. Evolution clinique et constatations anatomiques.

Operated upon in November, 1968, the last survivor of heart transplant recipients in those times has died on May 11, 1987, having survived 18 years and 6 months. The active life of this patient, however, was marred by episodes of graft rejection during the first post-operative years and by various incidents. It was mainly the complications of the immunosuppressive treatment that hampered his activities (osteoporosis) and provoked his death. Post-mortem examination confirmed that the heart was in good condition, found an active bronchial epithelioma and revealed iatrogenic lesions, namely adenomas, adenocarcinoma of the kidney and "regenerative" nodular hyperplasia of the liver with portal hypertension. Such lesions are observed in patients under long-term treatment with immunosuppressants. A "sleep apnoea" syndrome might have accounted for the formation of pulmonary hypertension lesions. The authors wish to pay their respects to this man who devoted himself to the service of other men.

[Reintervention on heart valve prostheses. Apropos of 78 cases]. / Les réinterventions sur prothèses valvulaires cardiaques. A propos de 78 observations.

78 patients with one or more prosthetic heart valves were reoperated on between 1972 and 1978, and comprised 12% of the work load of valvular surgery. There were two postoperative periods in which the incidence of reoperation was high: the first year, 38%, and the period between the 5th and the 8th year, 41%. The main causes of reoperation could be divided into two groups: those common to all valves with paravalvular leaks (25%), endocarditis (12%) being the principal causes, and those associated with particular valves: deterioration of Beall prosthesis 33%, and thrombosis mainly affecting the Bjork and Beall prostheses (25%). The operative mortality was 12%. The fact that urgent operation is required in severe cases is underlined. In the light of these results, the surgical indications of reoperation should be discussed at an earlier stage. These indications are based essentially on the clinical condition of the patient and objective confirmation by further investigation should not delay the operation, which, in our experience, has never been unnecessary.

[Ventricular arrhythmia following repair of Fallot's tetralogy. Apropos of 59 cases]. / Troubles du rythme ventriculaire après réparation de tétralogie de Fallot. A propos de 59 cas.

Fifty-nine patients operated for Fallot's tetralogy were reviewed over 3 years after surgery. The average age at surgery was 7.4 years (range 6 months to 37 years). The review included ECG, chest X-ray, echocardiography, exercise stress testing and Holter monitoring, completed by cardiac catheterisation in 10 cases and electrophysiological investigation in 4 cases. Forty-eight of the 59 patients (81.3 p. 100) had no signs of ventricular arrhythmia or only benign ventricular extrasystoles (Group I). Four patients (6.8 p. 100) had severe ventricular arrhythmias (Group II). Seven patients (11.9 p. 100) had one or more episodes of ventricular tachycardia (VT) (Group III) and, in 3 of these patients, VT was recorded during Holter monitoring or exercise stress testing. One patient in Group III died after reoperation, but there were no cases of sudden death in this series. The high risk patients Groups II and III) were operated late (after 5 years), had bi- or trifascicular block (7 out of 11 cases), ventricular extrasystoles on resting ECGs (9 out of 11 cases), cardiomegaly (6 out of 7 cases in Group III), echocardiographic dilatation of the infundibulum (6 out of the 8 patients undergoing echocardiography in Groups II and III). They had significant residual malformation but without right ventricular hypertension (as judged mainly by immediate postoperative data). Ventricular arrhythmias occurred over 6 years after surgery. However, none of the patients operated before 2 years of age had ventricular arrhythmias or VT with a mean follow-up period of 7.5 years, perhaps because LV function was protected.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical history and anatomic findings following the longest survival after cardiac transplantation]. / Histoire clinique et constatations anatomiques au terme de la plus longue survie après transplantation cardiaque.

The authors report the case history of the first patient in the world to have survived 18 and a half years with a heart transplant. This survival was marked by several episodes of rejection during the early years and various other incidents. The pathology encountered was primarily iatrogenic: diffuse osteoporosis sometimes limited the patient's activity. Two skin cancers and a lung cancer were diagnosed and treated. The patient died from progressive respiratory failure with pulmonary hypertension and signs of right ventricular failure. Pathological examination revealed a subnormal myocardium with a certain amount of overloading of the coronary arteries, confirmed the lung cancer and pulmonary hypertension and, most importantly, revealed the presence of nodular regenerative hepatic cirrhosis responsible for ascites during the last few months of life and a renal adenocarcinoma. These last two lesions are observed in immunosuppressed patients. The authors pay tribute to this patient who led an active and devoted life in the service of others.

[Selective tricuspid annuloplasty without prosthetic support]. / Annuloplastie tricuspidienne sélective sans support prothétique.

Two techniques of plastic surgery are currently used to treat tricuspid insufficiency: a prosthetic reductor or a continuous running suture. In the technique advocated here a double continuous suture is inserted into the tricuspid annulus, one running from the antero-septal to the antero-external commissures and the other, from the postero-septal to the antero-external commissures. When these two sutures are tied separately, the circumferences of the two parts of the annulus, which are diversely dilated, can be reduced. The authors have used this technique in 141 patients and a Carpentier's annulus in 41 patients. Perioperative mortality and 5-year survival were the same in both series, but the incidence of postoperative atrioventricular block was much lower in the first one. Another advantage of the double continuous suture technique is that foreign material is reduced to a minimum.

[Corneal changes in leprosy (report of an autochtonous case) (author's transl)]. / Les lesions cornéennes de la Lèpre. A propos d'un cas de lèpre autochtone.

The patient was affected by a lepromatous leprosy and had a unilateral oedema of the posterior layers of the cornea with a conjonctival hyperhemia. The authors review the various aspects of corneal changes in leprosy: -- paralytic and non specific changes in trigeminal paralysis; -- direct and specific changes: opacification of corneal nerves, a vascular keratitis, corneal leproma, disorders of the vascularisation either by pannus or by interstitial vascularisation. The epidemiological problems are briefly considered.