Body weight variation is not an independent factor in the determination of functional hypothalamic amenorrhea in anorexia nervosa.

OBJECTIVE: Functional hypothalamic amenorrhea (FHA) is one of the foremost manifestations in anorexia nervosa (AN), but a subset of patients have menses despite marked weight loss and underweight. The aim of our study was to investigate parameters potentially influencing FHA in AN. DESIGN AND METHODS: In this observational retrospective study, we selected 114 female patients with AN who completed a 12 months semi-residential rehabilitation program and a subsequent 12 months outpatient follow-up. We divided our sample into three groups: "Group 0" patients who experienced FHA and recovered their menses, "Group 1" persistent FHA, "Group 2" never experienced FHA, and looked for clinical and hormonal correlations. RESULTS: At the enrollment, the BMI was higher in Group 2 than in Group 1 (p = 0.0202), but the last follow-up weight was higher in Group 1 (p < 0.0001) despite persistent amenorrhea. At logistic regression, the higher BMI at which patients experienced amenorrhea was the main prediction factor for persistent FHA. Notwithstanding comparable leptin levels at admission, they improved significantly at discharge only in Groups 0 and 2 (p = 0.0054 and p = 0.0104, respectively). FT3 at admission was significantly higher in Group 2 than in Group 0 (p = 0.0249). CONCLUSIONS: FHA does not correlate strictly with body weight variations in AN patients, indicating a multifactorial origin, likely including an individual predisposition. Higher FT3 levels identify patients who continue having menses at extremely low BMI. AN patients with persistent FHA constitute a subgroup in whom estroprogestins should be considered after significant weight recovery to prevent prolonged tissue hypoestrogenism.

Stemming the Leak: A Novel Treatment for Gastro-Bronchial Fistula.

Laparoscopic sleeve gastrectomy (LSG) is a commonly used procedure in bariatric patients that often has excellent results. Despite its advantages, LSG is burdened by specific intraoperative and postoperative early and late complications. One of the life-threatening complications is gastric fistula, usually treated with a multidisciplinary surgical-endoscopic approach. In case of failure of the latter, alternative nonoperative techniques such as the use of autologous stem cells truly represents an innovative possibility, with only few cases described in literature. Here, we report the case of a 25-year-old man with post-LSG broncho-gastric fistula treated with application of autologous stem cells after the failure of the conventional surgical/endoscopic approach.

[Systemic sclerosis: Efficacy of intravenous immunoglobulins in severe cardiac involvement?] / Sclérodermie systémique : efficacité des immunoglobulines intraveineuses pour l'atteinte cardiaque sévère ?

BACKGROUND: The heart involvement in systemic sclerosis is frequent and can touch various sites. The prognosis in the presence of heart disease is poor, but few data are available about its management. CASE: We report the case of 48 years old woman with systemic sclerosis which presented severe heart involvement. She has severe heart failure, supraventricular arrhythmias and symptomatic pericarditis, which required surgical intervention and immunosuppressive drugs (steroids with rituximab). Despite this treatment, she has persistent severe heart impaired function and intravenous immunoglobulins have been initiated. She experienced progressively the improvement of dyspnea, of heart systolic ejection fraction and decrease of Rodnan scale. CONCLUSION: Our case illustrates a severe heart involvement in systemic sclerosis which have been improved by intravenous immunoglobulins.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. LEARNING POINTS: Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.

Genetic defects of ovarian TGF-ß-like factors and premature ovarian failure.

Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles; POF affects approximately 1-2% of women under the age of 40 yr, thus representing one major cause of female infertility. POF relevance is continuously growing because women tend to conceive always more frequently beyond 30 yr. Frequently, POF is the end-stage of an occult process [primary ovarian insufficiency (POI)]. POI is a heterogeneous disease caused by a variety of mechanisms. Though the underlying cause remains unexplained in the majority of cases, several data indicate that POI has a strong genetic component. These data include the existence of several causal genetic defects in human, experimental, and natural models, as well as the frequent familiarity. The candidate genes are numerous, but POF remains unexplained in most of the cases. Several recent evidences have driven the attention of researchers on the possible involvement of various elements belonging to the transforming growth factor ß family, which includes bone morphogenetic proteins, growth/differentiation factors, and inhibins. These peptides are produced by either the oocyte or granulosa cells to constitute a complex paracrine network within the ovarian follicle. Here, we review the studies reporting the genetic alterations of these factors in human and animal defects of ovarian folliculogenesis which support the fundamental roles played by these signals in ovarian morphogenesis and function.

Immunocytochemical localization of opsin, visual arrestin, myosin III, and calmodulin in Limulus lateral eye retinular cells and ventral photoreceptors.

The photoreceptors of the horseshoe crab Limulus polyphemus are classical preparations for studies of the photoresponse and its modulation by circadian clocks. An extensive literature details their physiology and ultrastructure, but relatively little is known about their biochemical organization largely because of a lack of antibodies specific for Limulus photoreceptor proteins. We developed antibodies directed against Limulus opsin, visual arrestin, and myosin III, and we have used them to examine the distributions of these proteins in the Limulus visual system. We also used a commercial antibody to examine the distribution of calmodulin in Limulus photoreceptors. Fixed frozen sections of lateral eye were examined with conventional fluorescence microscopy; ventral photoreceptors were studied with confocal microscopy. Opsin, visual arrestin, myosin III, and calmodulin are all concentrated at the photosensitive rhabdomeral membrane, which is consistent with their participation in the photoresponse. Opsin and visual arrestin, but not myosin III or calmodulin, are also concentrated in extra-rhabdomeral vesicles thought to contain internalized rhabdomeral membrane. In addition, visual arrestin and myosin III were found widely distributed in the cytosol of photoreceptors, suggesting that they have functions in addition to their roles in phototransduction. Our results both clarify and raise new questions about the functions of opsin, visual arrestin, myosin III, and calmodulin in photoreceptors and set the stage for future studies of the impact of light and clock signals on the structure and function of photoreceptors.

Regulation of arrestin mRNA levels in Limulus lateral eye: separate and combined influences of circadian efferent input and light.

Most animals experience daily changes in light and darkness. The retinas of many of these animals show concomitant rhythmic changes in the levels of mRNAs that encode proteins involved in the photoresponse. These changes may be circadian and independent of light, independent of circadian clocks and regulated by light, or regulated by a circadian clock and light. We have taken advantage of the organization of the Limulus visual system to examine the separate and combined effects of signals from a circadian clock and light on arrestin mRNA levels in photoreceptors. The clock that regulates photoreceptors in the lateral eye of Limulus is in the brain, and signals from the clock reach the lateral eye via activation of a well-characterized efferent projection in the lateral optic nerve. In the experiments described, clock-driven efferent input to the lateral eye was eliminated by cutting the lateral optic nerve, and light input to the lateral eye was eliminated by placing an opaque patch over the eye. Arrestin mRNA levels were quantified relative to 18s rRNA with a ribonuclease protection assay. We observed the following. In lateral eyes exposed to natural diurnal light and endogenous efferent nerve activity, the level of arrestin mRNA was higher during the day in the light than during the night in the dark. Circadian efferent nerve activity was necessary and sufficient to produce normal daily fluctuations in the level of arrestin mRNA. Light influenced arrestin mRNA levels only in eyes with intact and active efferent projections. We conclude that arrestin mRNA levels in lateral eye photoreceptors are controlled entirely by efferent nerve activity, and that light exerts its effects by modulating this output from the circadian clock. Light-stimulated changes in arrestin mRNA in the vertebrate retina may likewise require interactions between light-driven biochemical cascades and clock output.

All-optical switching and pulse routing in a distributed-feedback waveguide device.

Results of all-optical switching and pulse-routing experiments with a distributed-feedback multiple-quantum-well (MQW) nonlinear waveguide, operating at 1.55microm , are reported. The MQW material has been engineered, through the controlled introduction of defects, to lower the carrier lifetime from 2.5 ns to 280 ps. The energy required for switching is of the order of 1 pJ or less, the switching time is ~600 ps , and the on-off contrast exceeds 17 dB.

Does measurement of amniotic fluid index detect changes in amniotic fluid volume after second-trimester amniocentesis?

The objective of this study was to establish whether variations of amniotic fluid volume induced by second-trimester amniocentesis could be detected by serial measurements of amniotic fluid index. A total of 130 singleton pregnancies undergoing second-trimester amniocentesis for genetic indications were considered. Amniotic fluid index was measured at three different time intervals: 30-60 min before amniocentesis, immediately after the procedure, and 60 min after the procedure. Serial measurements were obtained either by a single operator (n = 55) or by the three independent operators (n = 75). Significantly lower amniotic fluid index values were demonstrated immediately after amniocentesis when compared with the pre-amniocentesis and subsequent measurements in the study design with both the single and multiple operators. No statistically significant changes were found between the first amniotic fluid index measurements and those obtained 1 h after amniocentesis. These results suggest that second-trimester amniocentesis induces a temporary decrease of amniotic fluid volume detectable by serial amniotic fluid index measurements, no longer evident 1 h after the procedure.

Evaluation of pulsatility index nomograms based on fetal biometry in small for gestational age fetuses.

Reference limits for the PI from the umbilical, middle cerebral, and renal arteries were constructed using BPD, AC, FL, and transverse cerebellar diameter as independent variables and their efficacy tested in a population of SGA fetuses. Therefore, 153 normal fetuses and 90 SGA fetuses with established dates between 20 and 40 weeks of gestation were considered. Normal fetuses showed a linear negative relationship between the PI from all the vessels investigated and all the biometric parameters considered. Although the BPD related better with the PI from the umbilical artery (r = 0.646) and the renal artery (r = 0.765) and the transverse cerebellar diameter related better with middle cerebral artery PI values (r = 0.510), no evident differences in fitting were found among the variables tested. In SGA fetuses the nomograms on BPD, AC, and FL significantly underestimated PI values in all the vessels studied when compared to the nomograms based on gestational age, while a similar ability in identifying abnormal PI values was found for nomograms based on gestational age and transverse cerebellar diameter. These newly developed nomograms based on transverse cerebellar diameter may prove useful in the evaluation of Doppler indices of fetuses with uncertain gestational age.

Analysis of factors influencing ventricular filling patterns in fetuses of type I diabetic mothers.

In an effort to determine the factors influencing the abnormal ventricular filling patterns of fetuses of type I diabetic mothers, Doppler flow velocity waveforms were recorded from fetal atrioventricular valves in 37 pregnancies complicated by type I diabetes immediately before an elective cesarean section. The ratio between the peak velocities during early passive ventricular filling and active atrial filling was calculated at the level of both atrioventricular valves and related to different factors including ventricular chamber wall thickness, heart rate, umbilical vein hematocrit and time to peak velocities values obtained at the outflow tract. Multiple stepwise regression demonstrated that the interventricular wall thickness, heart rate and hematocrit values significantly and independently affected the ratios between early and active ventricular filling from mitral and tricuspid valves. As a consequence all these factors should be taken into account in the interpretation of atrioventricular Doppler indices.

[Chemical and pharmacological research on pyran derivatives. XIII. Derivatives of 2H-pyrano/3,2-c/quinoline]. / Ricerche chimiche e farmacologiche su derivati piranici. XIII - Derivati della 2H-pirano[3,2-c]chinolina.

Treatment of N-alkylanilines or diphenylamine with N,N-dialkylethoxycarbonylacetamides in the presence of phosphorus oxychloride afforded 6-alkyl(phenyl)-4-dialkylaminopyrano [3,2-c] quinoline-2,5-(6H)-diones, two molecules of amide being involved in the reaction. In some instances 6-alkyl(phenyl)-4-alkylaminopyrano [3,2-c] quinoline-2,5(6H)-diones were obtained through a partial dealkylation of the amino group. Pharmacological evaluation of some compounds showed no activity on the CNS.

[Chemical and pharmacological research on pyran derivatives. VIII. Synthesis of 2-dialkylamino-7-methoxychromones and derivatives]. / Ricerche chimiche e farmacologiche su derivati piranici. Nota VIII - Sintesi di 2-dialchilammino-7-metossicromoni e derivati

2-Dialkylamino-7-methoxychromones were prepared by reaction of a m-methoxyphenol with N,N-dialkylethoxycarbonylacetamides in the presence of phosphorus oxychloride. Treatment of such compounds with 57% hydriodic acid resulted in the formation of the corresponding 7-hydroxy derivatives. These latter, treated with dialkylamines and formaldehyde, were transformed into the 8-dialkylaminomethyl derivatives. On the other hand the reaction of 2-dialkylamino-7-methoxychromones with morpholine and formaldehyde, in the presence of acetic acid, led to the formation of the corresponding 3-morpholinomethyl derivatives. Pharmacological investigation showed that 2-dialkylamino-7-hydroxy-chromones were without effect, whereas all other compounds tested had a clear, but generally weak, CNS stimulant activity.