Surgery First and Clear Aligners on Relapsed Condylar Hyperplasia.

ABSTRACT: Condylar hyperplasia is (CH) a mandibular malformation that involves a change in the size and morphology of the condylar neck and head. The CH is an abnormality that usually occurs unilaterally and affects equally both men and women. Its etiology is controversial in its own right. Under this condition, mandibular growth occurs in all the 3 planes of space, but more predominantly in one of them. Treatment protocols are variable, but one of the best treatment choices is high condylectomy. Compared to the past, the change in the treatment protocol, as well as the innovations in both surgical and orthodontic technology, allowed a simplification of the therapeutic path, reduced patient discomfort and ensured more stable long-term postsurgical results.The authors present a case of a 40-year-old female patient with relapsed of unilateral CH, treated surgically for the second time and with orthodontic treatment with clear aligners. The clear aligners orthodontic treatment is now considered one the best treatment orthodontic options. In this case, considering the relapse of the hyperplasia and the need of a new orthodontic treatment we decide to use this technique to reduce patient discomfort and teeth force appliance.

Synthesis and evaluation of a superabsorbent-fertilizer composite for maximizing the nutrient and water use efficiency in forestry plantations.

Reducing fertilizer use is a priority in the quest for sustainable forestry systems. In short rotation Eucalyptus plantations, NPK pellets are routinely added to the seedling's top soil layer at planting, potentially leading to increased seedling mortality, nutrient loss and environmental degradation. To address this triple challenge, the development of efficient fertilization practices is essential. In the present work, we synthesized a crosslinked acrylic-cellulosic superabsorbent composite (SAPH-BAL) containing small amounts of specific nutrients integrated in the polymer matrix. We analyzed the composite's chemical and rheological properties, and assessed the viability of Eucalyptus plantations supplied with it at planting. Physiological measurements confirmed the suitability of SAPH-BAL in greenhouse-grown potted seedlings subjected to different growth conditions, showing that it efficiently delivers nutrients while protecting seedlings from drought stress. Field experiments carried out at ten South American locations covering an ample range of environmental conditions confirmed the beneficial effect of SAPH-BAL on growth and survival in comparison to the conventional fertilization scheme (superabsorbent + 75 g NPK). Furthermore, it was found that plants treated with SAPH-BAL were less affected by the differences in rainfall regimes during the experiments compared to those fertilized conventionally. To the best of our knowledge this is the first report describing the successful use of superabsorbents for root targeted delivery of fertilizers in forestry operations.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Substance P expression in the gingival tissue after upper third molar extraction: effect of ketoprofen, a preliminary study.

The aim of this study was to evaluate substance P (SP) levels and the effect of a non-steroidal anti-inflammatory drug (NSAID), ketoprofen, on SP in the pericoronal gingival tissue after extraction of upper third molars. A sample of 20 young non-smoking systemically healthy adults of both sexes, with a healthy upper third molar to extract for orthodontic purposes, was selected. After extraction, a sample of the gingival tissue of the pericoronal region was collected with a sterile scalpel, placed into test tubes and kept frozen at -20°C until the SP determination. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into two groups: group 1 received a single dose of ketoprofen 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration before extraction. The patients were asked to complete a diary on the postoperative pain. A relevant amount of SP was measured in all the gingival samples. No statistically significant difference could be detected in SP expression between the two groups. In group 1 pain appearance was significantly delayed (6.2±0.13 hours) in comparison with group 2 (3.95±0.2 hours). In this small selected group of subjects and limited study design, preventive administration of ketoprofen did not significantly affect the gingival levels of SP, the clinical recommendation emerging is that of NSAID administration postoperatively but before pain appearance in order to optimize the management of pain of the patient.

Late treatment of orbital fractures: a new analysis for surgical planning.

Surgical treatment of orbital fractures should be performed without delay; in some cases acute management is not possible due to general conditions and might be delayed for weeks or months. In the latter case, the fractured fragments can consolidate improperly, causing secondary deformities of the orbital region with aesthetic and functional alteration. Surgical planning of secondary deformities is critical for adequate pre-operative planning. In the last decade an increasing number of dedicated software applications for surgical planning have been developed. Standard computed tomography (CT) or the relatively new cone beam CT can be used for diagnostic purposes, pre-surgical visual treatment outcome and virtual surgery. In this report, the authors propose their pre-operative planning analysis for surgical correction of secondary deformities of orbital fractures. The treatment of orbital fracture must, in fact, analyse not only the bone structures but the soft tissue and surrounding periorbital region. The position of the orbit in the space should be determined in relation to the surrounding structures compared to the contralateral side, if this is not affected by the trauma or pre-existing malformations.

Use of irradiate animal pericardium membrane for prevention of Frey's syndrome after parotidectomy.

BACKGROUND: Frey syndrome is a common complication that appears few months after parotid surgery with flushing and sweating of the parotid-temporal area during mastication. It presumably originates from an aberrant nervous regeneration in which the parasympathetic fibers of the parotid gland would combine themselves with the sympathetic fibers of the sweat glands and with the cutaneous vessels. AIM: In the present study we analyze the effectiveness of a collagenous membrane derived from animal pericardium (APM) to prevent Frey's syndrome after parotidectomy. MATERIALS AND METHODS: We studied a total of 40 patients with benign tumors of the parotid gland, including 30 patients with pleomorphic adenoma, 7 patients with Warthin tumor and 3 with basal cells adenoma. The patients were divided into 2 groups: group 1 (experimental n=20) executed superficial parotidectomy with replacement of bovine pericardial matrix (BPM); group 2 (control n=20) underwent superficial parotidectomy followed by reposition of superficial musculoaponeurotic system (SMAS) flap. All patients were questioned over their subjective symptom and tested with Minor's test after 12 months from the intervention and introduced in a follow-up of 3 years. RESULTS: Subjectively Frey syndrome was referred in 5% of patients in group 1 and in 10% in group 2, while 0 cases were observed in group 1 after the starch-iodine test, 2 cases in group 2 (10%). CONCLUSIONS: Considering the present results, although this study needs further implementation, we can affirm that BPM is a valid option in preventing Frey's syndrome whereas SMAS flap is not available.

Prevalence of growth hormone deficiency in adult polytransfused ß-thalassemia patients and correlation with transfusional and chelation parameters.

BACKGROUND: Dysfunction of GH-IGF-I axis has been described in many patients affected by ß-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. AIM: The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused ß-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. SUBJECTS AND METHODS: We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. RESULTS: We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. CONCLUSIONS: This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

Volumetric response of vertebrate hepatocytes challenged by osmotic gradients: a theoretical approach.

In this study we use a theoretical approach to study the volumetric response of goldfish hepatocytes challenged by osmotic gradients and compared it with that of hepatocytes from another teleost (the trout) and a mammal (the rat). Particular focus was given to the multiple non-linear interactions of transport systems enabling hypotonically challenged cells to trigger a compensatory response known as volume regulatory decrease or RVD. For this purpose we employed a mathematical model which describes the rates of change of the intracellular concentrations of main diffusible ions, of the cell volume, and of the membrane potential. The model was fitted to experimental data on the kinetics of volume change of hepatocytes challenged by anisotonic media. In trout and rat hepatocytes, experimental results had shown that hypotonic cell swelling was followed by RVD, whereas goldfish cells swelled with no concomitant RVD (M.V. Espelt et al., 2003, J. Exp. Biol. 206, 513-522). A comparison between data predicted by the model and that obtained experimentally suggests that in trout and rat hepatocytes hypotonicity activates a sensor element and this, in turn, activates an otherwise silent efflux of KCl - whose kinetics could be successfully predicted - thereby leading to volume down-regulation. In contrast, with regard to the absence of RVD in goldfish hepatocytes the model proposed suggests that either a sensor element triggering RVD is absent or that the effector mechanism (the loss of KCl) remains inactive under the conditions employed. In line with this, we recently found that extracellular nucleotides may be required to induce RVD in these cells, indicating that our model could indeed lead to useful predictions.

Polymorphonuclear leukocyte: rheology, metabolism and integrin pattern in vascular atherosclerotic disease and in type 2 diabetes mellitus.

Leukocytes, and in particular polymorphonuclear cells (PMN), play a role in the organ injury that characterizes the progression of vascular atherosclerotic disease (VAD) and diabetes mellitus (DM). We enrolled subjects with VAD, subjects with type 2 DM (DM2) and subjects with VAD and DM2. We evaluated the initial relative flow rate (IRFR) of PMN, using the St. George Filtrometer, the PMN membrane fluidity, labelling intact PMN cells with the fluorescent probe 1.4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH), the PMN cytosolic Ca2+ content marking the cells with the fluorescent probe Fura 2-AM and the PMN integrin profile using the flow cytofluorimetry. All these evaluations were effected at baseline and after activation with 4-phorbol-12-myristate-13-acetate (PMA). At baseline and after activation the IRFR did not distinguish normal subjects from any group of patients. The PMN membrane fluidity at baseline differentiated only normal from DM2 subjects, while after activation no significant variation of this parameter was observed in normal, VAD, DM2 and VAD-DM2 subjects. The PMN cytosolic Ca2+ content, at baseline, discriminated only normal from VAD subjects with DM2, while after activation a significant increase of this parameter was evident in DM2 subjects and in VAD subjects with DM2. Regarding the PMN integrin pattern we observed, at baseline and after activation, a complex and non-univocal behaviour. In conclusion, the PMN rheological and metabolic pattern found in these groups of patients showed only small functional alterations while the integrin pattern was significantly different from that of normal subjects and added specific elements which may have potential therapeutical implications.

Volumetric and ionic responses of goldfish hepatocytes to anisotonic exposure and energetic limitation.

The relationship between cell volume and K(+) transmembrane fluxes of goldfish (Carassius auratus) hepatocytes exposed to anisotonic conditions or energetic limitation was studied and compared with the response of hepatocytes from trout (Oncorhynchus mykiss) and rat (Rattus rattus). Cell volume was studied by video- and fluorescence microscopy, while K(+) fluxes were assessed by measuring unidirectional (86)Rb(+) fluxes. In trout and rat hepatocytes, hyposmotic (180 mosmoll(-1)) exposure at pH 7.45 caused cell swelling followed by a regulatory volume decrease (RVD), a response reported to be mediated by net efflux of KCl and osmotically obliged water. By contrast, goldfish hepatocytes swelled but showed no RVD under these conditions. Although in goldfish hepatocytes a net ((86)Rb(+))K(+) efflux could be activated by N-ethylmaleimide, this flux was not, or only partially, activated by hyposmotic swelling (120-180 mosmoll(-1)). Blockage of glycolysis by iodoacetic acid (IAA) did not alter cell volume in goldfish hepatocytes, whereas in the presence of cyanide (CN(-)), an inhibitor of oxidative phosphorylation, or CN(-) plus IAA (CN(-)+IAA), cell volume decreased by 3-7%. Although in goldfish hepatocytes, energetic limitation had no effect on ((86)Rb(+))K(+) efflux, ((86)Rb(+))K(+) influx decreased by 57-66% in the presence of CN(-) and CN(-)+IAA but was not significantly altered by IAA alone. Intracellular K(+) loss after 20 min of exposure to CN(-) and CN(-)+IAA amounted to only 3% of the total intracellular K(+). Collectively, these observations suggest that goldfish hepatocytes, unlike hepatocytes of anoxia-intolerant species, avoid a decoupling of transmembrane K(+) fluxes in response to an osmotic challenge. This may underlie both the inability of swollen cells to undergo RVD but also the capability of anoxic cells to maintain intracellular K(+) concentrations that are almost unaltered, thereby prolonging cell survival.

Protoplasmic pH modifies water and solute transfer in beta vulgaris root vacuoles.

Volume changes were studied in Beta vulgaris storage root vacuoles, using video microscopy, when exposed to hypotonic conditions. The osmotic gradient was either step-applied or progressively imposed in perfusion experiments. Preincubation at low pH (6.6) or with HgCl2 strongly reduced the vacuoles' water permeability, measured in step experiments. Furthermore, the volumetric response depended on the rate with which the aniso-osmotic condition was established. In perfusion experiments a "plateau value" (osmotic equilibrium or steady-state volume value) was observed, which was significantly lower than the theoretically expected one. Furthermore, if vacuoles were preincubated in presence of HgCl2 or at low pH and then the hypo-osmotic challenge was applied in perfusion experiments, a still lower "plateau value" was observed. This reduction was concentration-dependent and completely reversible. In these conditions, when HgCl2 concentration was 300 mM or medium pH was 6.6, the volume change was abolished. In other experiments, when urea iso-osmotically replaced mannitol, a reversible, pH-dependent volumetric response was observed. These results can be interpreted accepting that 1) mercury-sensitive water channels, present in the studied structure, were blocked by low pH during the hypo-osmotic challenge; 2) modification of water permeability prevents excessive swelling during the osmotic shock; 3) the effectiveness of this last mechanism depended on the osmotic challenge rate; and 4) additionally, urea reflection coefficients were also modified by reduced medium pH.

Functional characterization and localization of AQP3 in the human colon.

Water channels or aquaporins (AQPs) have been identified in a large variety of tissues. Nevertheless, their role in the human gastrointestinal tract, where their action is essential for the reabsorption and secretion of water and electrolytes, is still unclear. The purpose of the present study was to investigate the structure and function of water channels expressed in the human colon. A cDNA fragment of about 420 bp with a 98% identity to human AQP3 was amplified from human stomach, small intestine and colon by reverse transcription polymerase chain reaction (RT-PCR) and a transcript of 2.2 kb was expressed more abundantly in colon than in jejunum, ileum and stomach as indicated by Northern blots. Expression of mRNA from the colon of adults and children but not from other gastrointestinal regions in Xenopus oocytes enhanced the osmotic water permeability, and the urea and glycerol transport in a manner sensitive to an antisense AQP3 oligonucleotide, indicating the presence of functional AQP3. Immunocytochemistry and immunofluorescence studies in human colon revealed that the AQP3 protein is restricted to the villus epithelial cells. The immunostaining within these cells was more intense in the apical than in the basolateral membranes. The presence of AQP3 in villus epithelial cells suggests that AQP3 is implicated in water absorption across human colonic surface cells.

Functional characterization and localization of AQP3 in the human colon

Water channels or aquaporins (AQPs) have been identified in a large variety of tissues. Nevertheless, their role in the human gastrointestinal tract, where their action is essential for the reabsorption and secretion of water and electrolytes, is still unclear. The purpose of the present study was to investigate the structure and function of water channels expressed in the human colon. A cDNA fragment of about 420 bp with a 98 percent identity to human AQP3 was amplified from human stomach, small intestine and colon by reverse transcription polymerase chain reaction (RT-PCR) and a transcript of 2.2 kb was expressed more abundantly in colon than in jejunum, ileum and stomach as indicated by Northern blots. Expression of mRNA from the colon of adults and children but not from other gastrointestinal regions in Xenopus oocytes enhanced the osmotic water permeability, and the urea and glycerol transport in a manner sensitive to an antisense AQP3 oligonucleotide, indicating the presence of functional AQP3. Immunocytochemistry and immunofluorescence studies in human colon revealed that the AQP3 protein is restricted to the villus epithelial cells. The immunostaining within these cells was more intense in the apical than in the basolateral membranes. The presence of AQP3 in villus epithelial cells suggests that AQP3 is implicated in water absorption across human colonic surface cells

Biophysical properties of epithelial water channels.

The biophysical models describing the structure of water pores or channels have evolved, during the last forty years, from a pure 'black box' approach to a molecular based proposal. The initial 'sieving pore' in which water and other molecules were moving together was replaced by a more restrictive model, where water is moving alone in a 'single file' mode. Aquaporins discovery and cloning [G.M. Preston, T.P. Carroll, W.B. Guggino, P. Agre, Science 256 (1992) 365] leaded to the 'hour-glass model' and other alternative proposals, combining information coming from molecular biology experiments and two dimensional crystallography. Concerning water transfers in epithelial barriers the problem is quite complex, because there are at least two alternative pathways: paracellular and transcellular and three different driving forces: hydrostatic pressure, osmotic pressure or 'transport coupled' movements. In the case of ADH-sensitive epithelia it is more or less accepted that regulated water channels (AQP2), that can be inserted in the apical membrane, coexist with basolateral resident water channels (AQP3). The mechanism underlying the so-called 'transport associated water transfer' is still controversial. From the classical standing gradient model to the ion-water co-transport, different hypothesis are under consideration. Coming back to hormonal regulations, other than the well-known regulation by neuro-hypophysis peptides, a steroid second messenger, progesterone, has been recently proposed [P. Ford, G. Amodeo, C. Capurro, C. Ibarra, R. Dorr, P. Ripoche, M. Parisi, Am. J. Physiol. 270 (1996) F880].

Progesterone inhibition of water permeability in Bufo arenarum oocytes and urinary bladder.

The ovarian oocytes from Bufo arenarum (BAO) but not those from Xenopus laevis (XLO) would have water channels (WC). We now report that the injection of the mRNA from BAO into the oocytes from XLO increased their water osmotic permeability (Pi) (reduced by 0.3 mM HgCl2 and reversed by 5 mM beta-mercaptoethanol). A 30-min challenge with progesterone induced, 18 h later, a reduction of the mercury-sensitive fraction of Pf in the BAO (but not in XLO). The mRNA from BAO pretreated with progesterone lost its capacity to induce WC in the XLO, but the hormone did not affect the expression of the WC in XLO previously injected with the mRNA from BAO. Pf was also measured in urinary bladders of BAO. Eighteen hours after a challenge with progesterone, a reduction in the hydrosmotic response to oxytocin was observed. Finally, the mRNA from the urinary bladder of BAO was injected into XLO. An increase in Pf was observed. This was not the case if, before the mRNA extraction, the bladders were treated with progesterone. We conclude that the BAO WC share progesterone sensitivity with the oxytocin-regulated water channel present in the toad urinary bladder.

A Cationic Channel in the Guard Cell Tonoplast of Allium cepa.

Stomatal movements depend on an osmoregulation process in which swelling or shrinking of the guard cells opens or closes the stomatal pore. Ions and water fluxes are an essential aspect of guard cell osmoregulation. Thus far, studies of these fluxes have focused on the guard cell plasma membrane. Guard cells, however, are a multi-compartment system that includes a prominent vacuole, which has a primary role in turgor regulation. This study reports on a detailed characterization of an ion channel at the guard cell tonoplast of Allium cepa (onion). We used patch-clamp methodology with isolated tonoplast patches to study conduction and gating at the single channel level. A voltage-dependent outward-rectifying cationic channel (210 picosiemens) was the dominant conductance. In symmetrical solutions the channel displayed an ohmic behavior in its current-voltage relationship. It also showed a very large rectification in the open probability. The channel was predominantly cationic and its sequence of ionic selectivity was weak (Na+ > K+ > Rb+ > Cs+). The channel conductance was not affected by intravacuolar pH. Analysis of membrane patches with multiple channels showed that the probability of a channel to open was independent of the opening of the other channels present in the patch and that there was a conservation of the open probability for different channels. Ensemble records generated using a pulse protocol showed slow activation and deactivation kinetics. A first-latency analysis of single-channel records in response to protocols with different prepulse duration indicated that this channel has more than one closed state.

Vanadate inhibits blue light-stimulated swelling of vicia guard cell protoplasts.

When supplied under low chloride concentrations, vanadate inhibits the blue light-stimulated swelling of Vicia faba L. guard cell protoplasts in a dose-dependent fashion. The volume of guard cell protoplasts incubated in 10 mm K-imino-diacetic acid, 0.4 m mannitol, and 1 mm CaCl(2) remained essentially constant under 1000 mumol m(-2) s(-1) red light, but increased an average of 27% after 8 min of the addition of 50 mumol m(-2) s(-1) blue light to the background red light. At 500 mum, vanadate completely inhibits the response to blue light. Vanadate also inhibits the swelling of guard cell protoplasts stimulated by the H(+)-ATPase agonist fusicoccin. The vanadate sensitivity of the blue light-stimulated swelling implicates a proton-pumping ATPase as a component of the sensory transduction of blue light in guard cells.

Varicocele and puberty. A transversal and longitudinal survey.

The interest for varicocele in the determination of male infertility has increased during the last decades. Most researchers consider varicocele as the primary cause of male infertility, but recently another group of authors give it a secondary role in the alteration of spermatogenesis. We think that the major part of the controversy depends on an absence of a systematic approach to the problem. We give a primary importance to an accurate epidemiological evaluation which consists in a transversal and longitudinal survey of male subjects in puberal age. Our data show that left varicocele is practically inexsistent before the onset of puberty; the percentage incidence of this alteration increases progressively with puberal maturity and the tends to decrease slightly when maturity is complete. By correlating this pathology with puberty we can obtain more precise informations than when it is correlated to the regestrated age. The young patients who result suffering from varicocele, must be controlled carefully and periodically for the evaluation of the period and the opportunity of a therapeutic treatment.

Concomitant gonadotropin-releasing hormone agonist and menotropin treatment for the synchronized induction of multiple follicles.

In an effort to overcome possible interference by endogenous gonadotropin-ovarian hormone dynamics, desensitization of the pituitary gonadotropins by a gonadotropin-releasing hormone agonist (GnRHa) was achieved in 12 women with repeatedly failed attempts at multiple follicular stimulation. Eight women were scheduled for in vitro fertilization (IVF) and embryo transfer (ET), and 4 for gamete intrafallopian transfer (GIFT). Stimulation failure was characterized by premature luteinization, poor estradiol (E2) response, or inadequate follicular growth. The agonist was administered by nasal spray 500 to 600 micrograms/day beginning on days 21 to 23 of the menstrual cycle. A rapid desensitization occurred by 7.6 +/- 0.6 days (mean +/- standard error [SE]) following the initial dose. Gonadotropin stimulation was begun when pituitary and ovarian suppression was judged to be adequate. In response to gonadotropin stimulation, a continuous rise of E2 was observed in all patients with a mean of 989 +/- 46 pg/ml on the day of hCG. A cohort of synchronized follicles was recruited and matured. The mean number of growing follicles per patient was significantly higher (P less than 0.0001) in combined therapy than in previously failed cycles (8.0 +/- 0.3 versus 3.2 +/- 0.1). All the patients underwent oocyte retrieval and 94.3% of the harvested oocytes were preovulatory. A high fertilization rate (89.7%) of the inseminated oocytes occurred in IVF patients.

Induction of ovulation in normo-androgenic women, affected by primary hypothalamic amenorrhea, with chronic pulsatile administration of GnRH, using an automatic portable pump (Zyklomat).

Pulsatile administration of GnRH appears to be the most rational and physiological treatment of infertility in patients affected by hypothalamic amenorrhea. The authors conclude that the results obtained with this method of treatment in patients with severe hypothalamic amenorrhea suggest that the choice of pulsatile GnRH therapy is an effective and practical method for induction of ovulation.