Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

[Decision-making regarding treatment limitation after severe traumatic brain injury: A survey of French neurosurgeons]. / Modalités de décision de limitation thérapeutique chez les traumatisés crâniens sévères : enquête auprès des neurochirurgiens en France.

BACKGROUND/INTRODUCTION: In France, the law defines and prohibits "unreasonable obstinacy" and provides a framework for the subsequent decision to limit or to cease treatment. It also gives the person the right to appoint a trusted person and to draft advance directives regarding this issue. There have been few studies of neurosurgeons' involvement in decision-making in regard to treatment limitation after severe traumatic brain injury. AIM OF THE STUDY: The first aim of the study was to assess French neurosurgeons' adherence to the law on patients' rights and end of life which governs such decision-making. The second aim was to assess the prognostic and decision-making criteria applied by neurosurgeons. METHODS: A declarative practice and opinion survey, using a self-administered questionnaire emailed to all practising neurosurgeons members of the French Society of Neurosurgery, was conducted from April to June 2016. RESULTS: Of the 197 neurosurgeons contacted, 62 filled in the questionnaire. Discussions regarding treatment limitation were in all cases collegial, as required under the law, and the patient's neurosurgeon was always involved. The trusted person and/or family were always informed and consulted, but their opinions were not consistently taken into account. Advance directives were most often lacking (68%) [56; 80] or inappropriate (27%) [16; 38]. The most frequently used prognostic criteria were clinical parameters, intracranial pressure, cerebral perfusion pressure, and imaging, with significant interindividual variation in their use. The main decision-making criteria were foreseeable disability, expected future quality of life, and age. CONCLUSIONS: Neurosurgeons showed good compliance with legal requirements, except in the matter of calling for the opinion of an external consultant. Furthermore, this survey confirmed variability in the use of prognosis predictors, and the need for further clinical research so as to achieve more-standardized practices to minimise the subjectivity in decision-making.

Maternal intra- and postpartum near-miss following assisted reproductive technology: a retrospective study.

OBJECTIVE: To assess whether risk of severe maternal morbidity at delivery differs for women who conceived using assisted reproductive technology (ART), compared with those with a spontaneous conception. DESIGN: A cohort study using a prospectively maintained institutional database. SETTING: A tertiary university maternity hospital. POPULATION: All women delivering at Del Ponte Hospital, Italy, between 2005 and 2016. METHODS: Data from 650 ART-conceived pregnancies were compared with 22 803 spontaneously conceived pregnancies. We used multivariable analysis to estimate the odds of severe maternal morbidity at delivery associated with ART conception, adjusting for maternal demographic and health factors, gestational age, and mode of delivery. MAIN OUTCOME MEASURES: The World Health Organization criteria for potentially life-threatening conditions and near-miss maternal mortality were used. RESULTS: The incidence of near-miss in the entire cohort was 3.3 cases per 1000 births (95% confidence interval, 95% CI, 2.6-4.1). The crude prevalences of potentially life-threatening conditions and maternal near-miss were higher among ART than among non-ART deliveries (27.1 versus 5.7% and 2.6 versus 0.3%, respectively). The three most common causes of maternal near-miss cases were peripartum hysterectomy, transfusion of ≥5 units of red blood cells, and cardiovascular dysfunction requiring vasoactive drugs. The odds of a maternal near-miss at delivery were increased for ART-conceived pregnancies compared with non-ART-conceived pregnancies (adjusted odds ratio, aOR 3.61, 95% CI 1.61-8.09, for ART-conceived pregnancies with autologous oocytes; aOR 13.57, 95% CI 5.45-33.77, for ART pregnancies conceived with donor oocytes). CONCLUSION: Although we cannot exclude unmeasured confounding, we found that pregnancies conceived via ART, especially those conceived with donor oocytes, are at increased risk of maternal potentially life-threatening conditions and near-miss at delivery. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. TWEETABLE ABSTRACT: Conceiving through assisted reproductive technology increases the likelihood of maternal near miss.

Intraoperative identification of the negative motor network during awake surgery to prevent deficit following brain resection in premotor regions.

INTRODUCTION: Surgical resection in premotor areas can lead to supplementary motor area syndrome as well as a permanent deficit. However, recent findings suggest a putative role of the negative motor network in those dysfunctions. Our objective was to compare the functional results in two groups of adult patients who underwent the resection of a frontal glioma with and without resection of the negative motor networks. MATERIAL AND METHODS: Twelve patients (total of 13 surgeries) were selected for awake surgery for a frontal glioma. Negative motor responses were monitored during surgery at the cortical and subcortical levels. Sites eliciting negative motor responses were first identified then spared (n=8) or removed (n=5) upon oncological requirements. RESULTS: In the group with removal of the negative motor network (n=5), all patients presented a complete supplementary motor area syndrome with akinesia and mutism. At 3months, they all presented bimanual coordination dysfunction and fine movement disorders. In the group with preservation of the negative motor network (n=8), all patients presented transient and slight disorders of speech or upper limb, they all recovered completely at 3months. DISCUSSION: The negative motor network is a part of a modulatory motor network involved in the occurrence of the supplementary motor area syndrome and the permanent deficit after resection in premotor areas. Then, intraoperative functional cortico-subcortical mapping using direct electrostimulation under awake surgery seems mandatory to avoid deficit in bimanual coordination and fine movements during surgery in premotor areas.

[Orbital tumors arising from paranasal sinuses]. / Tumeurs orbitaires d'origine sinusienne.

Orbital tumors arising from paranasal sinuses comprise mucoceles and malignant ethmoidal tumors. Most often, anamnestic, clinical, and radiological data as well as endoscopic biopsy performed by an ENT surgeon provide the preoperative diagnosis. If the tumor is benign, surgery can cure the patient. It is associated with chemotherapy and radiotherapy if the tumor is malignant.

[Imaging follow-up of post-traumatic myelomalacia]. / Evolution d'une myelomalacie post-traumatique vers une syringomyelie: suivi iconographique.

The authors report a case of secondary worsening of neurological symptoms in a patient 2 months after cord injury at T5 causing paraplegia. The MRI showed myeolomalacia, which appears as cord oedema, located in the grey matter, extending increasingly from the initial lesion (eighth thoracic vertebra) to the bulb. This cord lesion known as grey matter cytotoxic oedema, evolved into a syringomyelic cavity.

[Subdural empyema in children: therapeutic strategy. Five cases]. / Empyèmes sous-duraux de l'enfant: stratégie thérapeutique. A propos de cinq cas.

We report a series of five subdural empyema (SDE) in children and young adults treated in the same neurosurgical department. These five cases were reviewed retrospectively. There were four boys and one girl, aged from three months to 18 years at time of diagnosis (median age: 7 years). SDE following intracranial surgery were excluded from the study. All patients were treated surgically (burr hole evacuation or craniotomy, repeated in some cases), followed by intravenous antibiotic therapy (mean time: 52 days) adapted to the micro-organism. Only the two patients treated by large craniotomy at first had a single surgical procedure. Involved micro-organisms are as follow: Streptococcus intermedius (n=2), Streptococcus pneumoniae (n=1), Escherichia coli (n=1), absence of any identified micro-organism (n=1). The five patients are alive (median follow-up: 22 month) without any sequelae. We advocate an aggressive surgical treatment of SDE in children with a large bone flap to allow the surgeon to remove pus and membranes as much as possible, even in the interhemispheric fissure, followed by intravenous appropriate antibiotherapy and eradication of the source of infection. Even this "aggressive" treatment may sometimes not avoid re-operation. A careful follow-up is mandatory, because of the high risk of recurrence.

[Childhood diencephalic pilocytic astrocytoma. A review of seven observations]. / Les astrocytomes pilocytiques du diencephale de l'enfant. à propos de sept observations.

BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the central nervous system mostly arising in children and young adults. Management of diencephalic PA is a difficult challenge. Surgical treatment has to cope with both the difficulties of deep location and eloquent area tumors. MATERIALS AND METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3) of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age was 111 months. Median follow-up for the series was 125 months. Tumor locations were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a shunting procedure was performed in 3 patients, a direct surgical approach in 5 patients (gross total removal: 2; partial removal: 3) and one patient had only a biopsy. Three children were re-operated. Three patients were treated by radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children. RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184 months). Median survival rate was 42 months (3.5 years). Three children died, two by tumor progression and one death related to late side-effects of RT. Four patients have a good quality of life with GOS I (n = 3) or II (n = 1). We observed tumor regression in two patients at 1 and 17 years after the beginning of treatment. Correct diagnosis was only made for two cases at the initial pathological examination. CONCLUSION: The course of diencephalic PA is still unpredictable. The tumor can be controlled by a partial surgical removal, and a residual tumor can sometimes decrease in size after surgery. Gross total removal of these tumors, although difficult, may be performed. With cranial navigation systems, the risk is low. Pathological diagnosis is sometimes difficult to assess.

Oral cancer mortality trends in Brazilian geographical regions from 1996-2001

The purpose of this study was to analyse the oral cancer mortality trends in Brazil by geographic region, age and sex, from 1996 to 2001. The Brazilian Ministry of Health database DATASUS and the Brazilian Institute of Geography and Statistics were used as the source of data. Oral cancer mortality rates per 100,000 population were estimated. Statistical analyses comprised estimates of oral cancer mortality rates, grouped according to the study variables, in 1996, 1997, 1998, 1999, 2000 and 2001; also, the three-year periods 1996-1998 and 1999-2001 were analysed, allowing the oral cancer mortality trends between these two periods to be calculated. For comparison, in each geographical region, the ratio between two death rates (related to period or sex) was calculated. In the period 1996-2001, a total of 25,972 deaths due to oral cancer were reported, giving a mortality rate of 2.67. The rates for the periods 1996-1998 and 1999-2001 were 2.53 and 2.73, respectively, showing a slight increase in the rate. There was a predominance of oral cancer in males with a male/female ratio of approximately 4. All regions exhibited an increase in mortality rates, with the exception of the Southeast region. From 1996 to 2001, the average mortality rates were 3.55 and 3.58 for the Southeast and South regions, and 1.94, 1.41, and 0.86 for the Mid-West, Northeast, and North regions, respectively. Over the age of 40, oral cancer mortality rates were seen to increase rapidly with age. Oral cancer mortality increased in all regions, exceptin the Southeast, and was considerably higher among males and older individuals.

Molecular characterization and expression of p63 isoforms in human keloids.

Keloids are benign skin tumors that develop following wounding. A cDNA product from human keloid specimens was identified using the differential display technique. The full-length cDNA was cloned by RT-PCR using human keloid mRNA as template. The predicted product of the cDNA was found to be 99% identical to the DeltaN-p63 gamma isotype of p63, a transcription factor that belongs to the family that includes the structurally related tumor suppressor p53 and p73. The DeltaN-p63 isotype lacks the acidic N terminal region corresponding to the transactivation domain of p53. Since this can potentially block p53-mediated target gene transactivation, it may serve as a dominant-negative isoform. Real-Time RT-PCR analysis of RNAs from normal skin tissue and keloids showed that the DeltaN-p63 isotype is specifically expressed in keloids, but is virtually undetectable in normal skin. Immunostaining of p63 in normal skin revealed that only basal cells of the epithelium expressed the protein, while in keloid tissues the antigen was detected in the nuclei of cells scattered through all layers of the epithelium and in fibroblast-like cells in the dermis. These results may indicate that aberrant p63 expression plays a role not only in malignant tumors but also in benign skin diseases that show hyperproliferation of epidermal cells in vivo. Moreover, this isoform of p63 could serve as a specific molecular marker for this human disease.

[Pleomorphic xanthoastrocytoma. A review of five observations]. / Le xanthoastrocytome pléomorphe. A propos de cinq observations.

BACKGROUND AND PURPOSE: We present a review of five patients who developed pleomorphic xanthoastrocytomas, presenting the clinical features, pathology findings and therapeutic approach of these rare tumours which almost always occur in children and young adults. METHODS: This paper is a retrospective study of five patients (three males and two females), treated from 1985 to 1996. RESULTS: Seizure was the most frequent symptom. The tumor was located in the temporal or temporo-parietal lobe in two patients, in the parietal lobe in one, the frontal in one and in hypothalamus and third ventricle in the final patient. To our knowledge, no case of pleomorphic xanthoastrocytoma located in the area of hypothalamus/third ventricle has been reported in the literature. All patients underwent surgery which was complete for two patients, subtotal for two others and partial for one. Four were given post-operative cerebral radiation therapy (two recurrences and malignant transformation and two erroneous diagnoses) (mean dose: 44.75 Gy), for two patients surgery was followed by chemotherapy. One patient was lost for follow-up. Two patients presented at least one tumor recurrence. Two died from malignant transformation. Two patients are alive without recurrence at 12 and 16 years from diagnosis with excellent quality-of-life (Glasgow Outcome Scale=I). CONCLUSION: Surgery is the gold standard treatment. Prognosis is very good (except for malignant transformation), so that a close long-term clinical and radiological follow-up is mandatory.

[French neurosurgical practice in Neuro-Oncology (national survey--part I)]. / Neurochirurgie et neuro-oncologie: état des lieux (I). Généralités, plan cancer, enquête nationale.

OBJECTIVE: The aim of this work is to summarize the elements of the "Cancer Plan" applicable to neurosurgical practice, and to give the results of a national inquiry concerning the daily practice of Neuro-Oncology from the neurosurgical point of view. METHOD: The Neuro-Oncology Group of the French Society of Neurosurgery has submitted a questionnaire to every department of Neurosurgery in France. RESULTS: The response rate of the public centers was 96.5%. Moreover, responses were available from 7 private centers. The results are detailed in the text. CONCLUSION: This national survey highlights the interest and implication of French neurosurgeons in the field of Neuro-Oncology. But also, to be in accordance with the guidelines for good clinical practice, the importance of developing official neuro-oncological networks in order to offer the best access to clinical and fundamental data and hence optimise patient's care. The publication of the "Cancer Plan", the creation of a National Neuro-Oncology Group, and the results of this survey (actual multidisciplinary approach, better information and transparency, individualized care of the patients), are in the line with updating our daily practice, even though discrepancies remain among centers. French neurosurgeons must continue along the same path, but at the same time there is a need for additional help to definitely reach a truly, and homogeneous, optimized care of neuro-oncological patients.

Clinical evaluation of glass ionomers used as fissure sealants: twenty-four-month results.

This study evaluated the twenty-four-month retention and effectiveness in dental caries prevention, of Vitremer and Ketac-Bond glass ionomers used as occlusal sealants. The initial sample consisted of 200 school children ages six to eight years whose permanent first molars were sound. The children were divided into two experimental groups (group 1 Vitremer; group 2 Ketac-Bond) and a control group (group 3 unsealed molars). Statistical analysis (Mann-Whitney test) revealed that there were statistically significant differences between the retention levels of the experimental groups A and B in the three evaluation periods (six-, twelve- and twenty-four-month) with Vitremer showing superior results. As to caries incidence, there was a statistically significant difference (chi 2 test) between the experimental groups (A and B) and the control group indicating that glass ionomers are effective for prevention of caries in the occlusal surfaces. Two independent variables were correlated with the presence of caries or that of a restored tooth after twenty-four months (odds ratio) revealing that children who presented white spots (WS) had a probability of presenting caries or restorations that was 5.0, 3.07 and 1.93 times greater at six, twelve, and twenty-four months, respectively than that of children who did not show WS in the experimental groups A and B and in the control group, respectively. The variable represented by the "dmf" index showed a statistically significant correlation (chi 2 test) in the control group, in which there was a 3.26 times greater probability of children presenting a "dmf" index equal to or greater than 1 in the development of caries or who presented a restored tooth in relation to those who did not have a history of caries ("dmf" = 0).

Galanin-like immunoreactivity in the brain and pituitary of the "four-eyed" fish, Anableps anableps.

The distribution of galanin (GAL)-like immunoreactivity was investigated in the brain and pituitary of the "four-eyed" fish, Anableps anableps. GAL-immunoreactive (GAL-ir) perikarya were located in the area ventralis telencephali pars supracommissuralis, nucleus preopticus periventricularis, nucleus preopticus pars parvocellularis, nucleus preopticus pars magnocellularis, nucleus lateralis tuberis ventralis, nucleus lateralis tuberis lateralis, and nucleus lateralis tuberis posterior. A few scattered, GAL-ir neurons were also observed in or adjacent to the nucleus recessus lateralis, nucleus recessus posterioris and lobus facialis (VII). GAL-ir fiber networks were widespread in the brain, with a comparatively higher density in the ventral telencephalic, preoptic and infundibular regions. The neurohypophysis showed GAL-ir innervation and there were GAL-ir cells in the adenohypophysis. The presence of GAL-ir cells in the hypothalamus and in the pituitary is an important asset for the supposed role of GAL-like peptide in neuroendocrine regulation of brain and pituitary functions.

FMRFamide in the amphibian brain: a comprehensive survey.

Mapping of FMRFamidergic neural circuitry in the amphibian brain has been done by immunohistochemical methods. Comparative evidence suggests that there are similarities and differences in the overall pattern of distribution of FMRFamide-ir elements in the brain among the three amphibian orders and within each order. FMRFamide is expressed in neurons in some circumscribed areas of the brain. A part of these neurons is concentrated in classical neurosecretory areas of the hypothalamus in a bilaterally symmetrical fashion. Similar neurons occur occasionally in the midbrain, but are virtually absent from the hindbrain. Anurans are unique among amphibians to show FMRFamide neurons in the medial septum and diagonal band of Broca. A viviparous gymnophione is known to possess a small population of such neurons in the dorsal thalamus. Together, the FMRFamide neurons contribute to an extensive fiber network throughout the amphibian brain. Descriptive developmental studies suggest that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the route of the vomeronasal-olfactory-terminal nerve complex. Olfactory placodal ablation in an anuran and a urodele provide experimental support to this contention. Other FMRFamide neuronal cell groups, in the hypothalamus and dorsal thalamus, are supposed to arise from non-placodal precursors. The neuroanatomical distribution (projection of immunoreactive processes to areas of the fore-, mid-, and hindbrain as well as to cerebrospinal fluid, co-localization with other neuropeptides, and presence in the median eminence) has furnished morphological correlates of possible functions of FMRFamide in the amphibian CNS. While amphibian FMRFamide-like or structurally related peptides remain to be isolated and characterized, the sum of the distribution pattern of FMRFamide-like immunoreactivity suggests that it may act as a neurotransmitter or a neuromodulator, and also may have endocrine regulatory functions.

Intrasexual and intersexual dimorphisms of the red salmon prosencephalon.

Intrasexual as well as intersexual dimorphisms were found in the prosencephalon and mesencephalon of adult Oncorhynchus nerka (red/sockeye salmon). These dimorphisms are concerned with the position of the preoptic nucleus, nucleus lateralis tuberis, habenula, third ventricle, tectal ventricles, preoptic recess, recessus lateralis, horizontal commissure, posterior commissure, and toral commissure. The intrasexual dimorphism was characterized by either a rostral ("r"-pattern) or a caudal ("c"-pattern) position of the preoptic region as well as varying locations of other structures within the prosencephalon. As compared to "c"-pattern fish, the preoptic nucleus and nucleus lateralis tuberis were located more rostral, and the habenula was positioned further caudal, in "r"-type animals. The intersexual dimorphism was also characterized by different positions of the structures listed above. With the exception of the preoptic nucleus, all of these were located further rostral in "r"-pattern females than in type "r" males. In "c"-pattern females, they were positioned further caudal than in type "c" males. The number of neurons in the parvocellular and in the magnocellular portion of the preoptic region differed in the two genders with respect to "r"- as well as "c"-pattern fish. Males had more neurons than females in both the magno- and the parvocellular subdivisions of the preoptic region. In "r"- and "c"-pattern fish, the average size of magnocellular preoptic neurons was larger in females than in males. The observed intersexual variations may reflect gender-specific differences in the control of the pituitary. Functional correlates of intrasexual dimorphism are obscure.

Localization of FMRFamide-like immunoreactivity in the brain of the viviparous skink (Chalcides chalcides).

Neuroanatomical distribution of FMRFamide-like immunoreactivity was investigated in the brain and olfactory system of the viviparous skink, Chalcides chalcides. In the adult brain FMRFamide immunoreactive (ir) perikarya were observed in the diagonal band of Broca, medial septal nucleus, accumbens nucleus, bed nucleus of the anterior commissure, periventricular hypothalamic nucleus, lateral forebrain bundle, and lateral preoptic, subcommissural, suprachiasmatic and lateral hypothalamic areas. This pattern was seen in both male and female brains. Though all major brain areas showed FMRFamide-ir innervation, the densest ir fiber network was observed in the hypothalamus. During development, ir elements were observed for the first time in embryos at mid-pregnancy. FMRFamide perikarya were located along the ventral surface of the vomeronasal nerve, in the olfactory peduncle mediobasally, as well as in the anterior olfactory nucleus and olfactory tubercle. Furthermore, some ir neurons were observed in the rhombencephalic reticular substance; however, the ir fiber network was poorly developed. Later in development FMRFamide-ir neurons appeared also in the bed nucleus of the anterior commissure as well as the rhombencephalic nucleus of solitary tract and the dorsal motor nucleus of vagus nerve. In juveniles, the distribution profile of FMRFamide immunoreactivity was substantially similar to that of the adults, with a less widespread neuronal distribution and a more developed fiber network. Ontogenetic presence of FMRFamide immunoreactivity in the nasal area has been linked to the presence of a nervus terminalis in this reptile.

Development and distribution of FMRFamide-like immunoreactivity in the toad (Bufo bufo) brain.

By using immunohistochemistry, we studied the development and distribution of the FMRFamide-like immunoreactive (ir) neuronal system in the toad brain during the ontogeny. In addition to this, experimental evidence was provided to show that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the olfactory pathway. During early development, within the brain, FMRFamide-ir perikarya first appeared in the periventricular hypothalamus. Later in development, FMRFamide-ir cells were visualized in the rostralmost forebrain simultaneously with similar ir cells in the developing olfactory mucosa. Selective ablation of the olfactory placode(s), prior to the appearance of the first FMRFamide-ir cells in the brain, resulted in the total absence of ir cells in the telencephalon (medial septum and mediobasal telencephalon) of the operated sides(s). The preoptic-suprachiasmatic-infundibular hypothalamus-located FMRFamide-ir neurons were not affected by olfactory placodectomy, arguing that they do not originate in the placode. This result points to the placode as the sole source of such neurons in the rostral forebrain.