Familial 1.1 Mb deletion in chromosome Xq22.1 associated with mental retardation and behavioural disorders in female patients.

We report on a 7-year-old girl with severe mental retardation (MR), autism, micro-brachycephaly, generalized muscle hypotonia with distal hypotrophy of lower limbs, scoliosis and facial dysmorphisms. Array-CGH analysis identified a 1.1 Mb deletion of chromosome Xq22.1. Further analysis demonstrated that the deletion was inherited from her mother who showed mild MR, short stature, brachycephaly, epilepsy and a Borderline Personality Disorder. Microsatellite segregation analysis revealed that the rearrangement arose de novo in the mother on the paternal X chromosome. The deleted Xq22.1 region contains part of the NXF gene cluster which is involved in mRNA nuclear export and metabolism. Among them, the NXF5 gene has already been linked to mental retardation whereas NXF2 protein has been recently found to be partner of FMRP in regulating Nxf1 mRNA stability in neuronal cells. The dosage imbalance of NXF5 and NXF2 genes may explain the severe phenotype in our patient.

Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.

BACKGROUND: Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. METHODS: To assess further the clinical implications of this novel 15q13.3 microdeletion syndrome, 18 new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. RESULTS: The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognisable phenotype, but psychiatric disease was noted in 2 of 4 patients. CONCLUSIONS: Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly used paradigm in the diagnostic setting that aberrations inherited from a phenotypically normal parent are usually without clinical consequences.

Serum leptin concentrations in obese women with Down syndrome and Prader-Willi syndrome.

We have evaluated serum leptin concentrations in two forms of genetic obesity. The subjects examined were eight women with Down syndrome and eight women with Prader-Willi syndrome. All patients were in the reproductive age range and were obese (body mass index > or = 27 kg/m2). Plasma leptin values, analyzed as a function of body mass index showed a statistically significant correlation in both Prader-Willi (r = 0.985; p < 0.001) and Down syndrome patients (r = 0.943; p < 0.001). Obese Down syndrome women exhibited significantly lower leptin values (10.8 +/- 1.1) as compared to patients with Prader-Willi syndrome (31 +/- 2.6; p < 0.01). The linear correlation between leptin and insulin in the two groups of patients was not statistically significant. The data suggested that obesity in Prader-Willi subjects could be caused by failure of leptin to reach its target in the brain, as a consequence of defects in the receptor or in postreceptor processing, whereas data on obese patients with Down syndrome could be due to a different pathogenetic origin.

[Mezlocillin in short-term obstetrico-gynecologic prophylaxis]. / La mezlocillina nella profilassi ostetrico-ginecologica short-term.

The present study examines a sample of 98 patients aged 18-77 (mean age 57) and awaiting obstetric or gynaecological surgery who were given short-term prophylaxis with mezlocillin. The overall success rate was 83.67%, partial success 14.28% (against 81% in the controls). In addition to the benefits of a shorter hospital stay and lower operating costs, the treatment produced no side effects.

Clinical experimental considerations on the presence of set uterine pacemakers.

The authors studied the physiology of human uterine muscle contraction. Clinical experimental results obtained from elementary electrophysiological, electrohysterographic and pharmacological studies using PGs suggested that uterine muscle contraction does not originate in "pacemaker" areas. These data also showed that the electric phenomenon is not propagated along preferential "rails".

Electromyographical study of uterine activity in the human during labour induced by prostaglandin F2 alpha.

In full-term pregnant women, electrical and mechanical activity of the uterus was monitored throughout the course of labour promoted by intravenous infusion of Pg F2 alpha. The recorded potentials were mostly biphasic and characterized by their long duration ranging from 1 to 2s. A wide range of potential amplitudes (100 microV to 1.8 mV) was observed according to the various patients. Early at the beginning of labour induction, the electrical complexes firing at various uterine sites were proved to be in close relationship and also well correlated with the mechanical events. This feature remained unchanged during labour. Potential amplitudes also remained unchanged during the same period of time. Under these conditions, improvement of uterine coordination does not appear to be the mechanism by which the increase of uterine contractile strength, necessary to expel the fetus, is obtained at the end of gestation.

A new cervical perfusion method for induction of labor with prostaglandins.

PIP: 144 patients aged 18-41 were observed to study a new method of cervical perfusion of prostaglandins (PGs) to induce labor and missed abortion. 46 patients were primigravidae, 86 had a normal pregnancy, and 58 had missed abortion. Duration of gestation was 37-42 weeks, and duration of amenorrhea in case of missed abortion was 16-34 weeks. Induction of labor with oxytocin had been unsuccessful in all patients. A new technique of local perfusion of PGs directly into the cervix was attempted. In pregnant women 10 mg of PGF2alpha was diluted in 1000 ml of saline and infused; the initial concentration of 1-2 mcg/minute was increased every 2 hours. In cases of missed abortion 40 mg of PGF2alpha was diluted in 800 ml of saline; initial concentrations ranged from 5 to 10 mcg/minute and were increased every 2 hours. Mean delivery time was 6 hours 50 minutes; mean abortion time was 9 hours 55 minutes. 6 patients underwent cesarean section. When the uterine activity was analyzed in terms of amplitude and frequency of contractions it showed a maximum from 1 1/2 hours from beginning of labor, up to the 3rd hour of observation. In patients with missed abortion the maximum activity was recorded after the 2nd hour. Cardiotocographic curves, fetal heart rate, and clinical tests were normal. There were no complications, but only vomiting in 4 patients, and mild diarrhea in 9 patients. Labor was immediate in all patients, the latent phase exceeding 6 minutes in only 1 case; a contractile response was normally obtained after 30-40 seconds. In patients with incomplete abortion, the basal tone increased more rapidly than in pregnant patients while staying within the limits of safety. There were no pathologic or other changes in the genital organs at check up. Further studies on the effectiveness and safety of PGs are needed.^ieng

HGH behaviour at term of pregnancy and during puerperium.

Human growth hormone (HGH) has been measured in the plasma of 30 subjects at term of pregnancy, at 96 and at 144 h after delivery. The subjects were then selected into three groups: 10 were studied in basal conditions, 10 were given pyridoxine, 10 were given enantate testosterone and valerianate estradiol. In the first group the correlation index (t of Student) was not significant showing the lack of correlation among the tested averages. IN the second group the index of Student was weakly significant (t = 2.36, p less than 0.05). In the third group the Authors found a high representative correlation between the term of pregnancy and the 144th hour after delivery (t = 3.81, p less than 0.01) and between the 96th and 144th hour after delivery (t = 2.95, p less than 0.01).

Hormone profile of T3, T4 at the end of pregnancy and during puerperium.

The Authors have studied the T3, T4 and TBG behaviour at the end of pregnancy and after 96 h and 144 h from delivery in 25 pregnant women. The patients have been randomly divided into two groups: the first was studied in basal conditions and the second after administration of enantate testosterone and valerianate estradiol. In the first group T3 and T4 values increased slightly. A higher increase was noticed from the 96th to the 144th h from delivery. In the second group T3 and T4 values were discording.