Onset and progression of primary torsion dystonia in sporadic and familial cases

Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 ± 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 ± 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 ± 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.     

Seasonal plasma and intraovarian sex steroid profiles, and influence of temperature on gonadotropin stimulation of in vitro estradiol-17 beta and progesterone production, in Rana esculenta (Amphibia: Anura)

Seasonal plasma and intraovarian estradiol-17 beta (E) and progesterone (P) fluctuations were studied by specific radioimmunoassay in the frog, Rana esculenta. Moreover, incubations of ovine-luteinizing hormone (oLH)-stimulated ovarian pieces at two different temperatures (15 and 24 degrees) have been carried out in order to evaluate the dependence of E and P output on this exogenous factor. Estradiol showed similar changes in plasma and ovaries, while P profile was better evidenced in the gonads since this hormone fluctuated in plasma, giving pulses of difficult interpretation. A shift from E to P production by the ovary near the ovulatory period (February-March) was noted. In vitro experiments were carried out using approximately equal-sized ovarian fragments containing follicles ranging from 0.7 to 1 mm and classified as early vitellogenic. High temperature induced oLH-stimulated P production within 6 h, while E increased after 24 h concomitantly with a P decline. At 15 degrees the stimulatory effect of oLH was achieved only on E output in the incubation medium after 24 h. In conclusion, our results in the frog, R. esculenta, show that E and P intervene at peak values separately during the annual cycle and that the temperature has an important role in the regulation of the steroid hormone-releasing activity.     

Molecular forms of immunoreactive gonadotropin-releasing hormone in hypothalamus and testis of the frog, Rana esculenta

The hypothalamus and the testis of the frog, Rana esculenta, contain gonadotropin-releasing hormone (Gn-RH)-like peptides which are recognized by an antiserum raised against mammalian Gn-RH. Two molecular forms which coelute with synthetic chicken II and salmon Gn-RH from reverse-phase HPLC were distinguished in the hypothalamus. A single peak coeluting with synthetic chicken II Gn-RH was present in the testis.     

Analysis of blink rate in patients with blepharospasm.

The blink rate (BR) during rest, conversation, and reading was assessed in 50 patients with blepharospasm (BS) and in 150 healthy subjects. BR at rest and during conversation was higher in patients with BS. Moreover, 76% of patients had BR higher at rest than during conversation, whereas in 74% of controls, BR was higher during conversation than at rest. The sensitivity and specificity of two parameters (value of BR at rest and pattern rest-BR higher than conversation-BR) in discriminating patients and controls were computed. The best fit was obtained with a rest-BR above 27 blinks per minute. When the two parameters were combined (rest-BR above 27 blinks per minute together with the pattern rest-BR higher than conversation-BR), we obtained a 92.3% sensitivity and a 82.0% specificity in discriminating between BS patients and controls. These findings indicate that specific features of BR can be associated with BS, suggesting that the analysis of BR might be helpful for the diagnosis of BS in early stages.     

Diarrhoea in jaundiced neonates treated with phototherapy: role of intestinal secretion.

Thirty jaundiced neonates with diarrhoea who were being treated with phototherapy and 30 matched control infants were studied to try and find out the cause of the diarrhoea. Faecal osmolality and electrolyte concentrations were measured, which gave clear evidence that the diarrhoea arose from intestinal secretion. Rectal water and electrolyte absorption in 10 jaundiced infants receiving phototherapy, in 10 jaundiced infants not receiving phototherapy, and in 10 healthy controls was measured with a rectal dialysis bag. A further group of eight jaundiced infants was also studied both during and after phototherapy to document the reversal of ion transport changes. Absorption of water, sodium chloride, and potassium was significantly impaired in the patients receiving phototherapy compared with each of the control groups. Such impairment was transient, as it was not apparent when the jaundice faded and phototherapy was stopped. These data show that the colon plays a part in the pathogenesis of secretory diarrhoea and that both hyperbilirubinaemia and phototherapy are necessary for such an effect to develop.     

Endocannabinoid System in First Trimester Placenta: Low FAAH and High CB1 Expression Characterize Spontaneous Miscarriage

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were the first endocannabinoids to be characterized, that bind two G protein-coupled receptors, CB1 and CB2. AEA synthesized by multiple pathways, including NAPE-specific phospholipase D (NAPE-PLD) and degraded by the fatty acid amide hydrolase (FAAH). AEA levels are critical in regulating embryo development and the “window” of implantation. We examined the expression of nape-pld mRNA, CB1 and FAAH in human placenta hypothesizing that their altered signaling may contribute to spontaneous miscarriage. First trimester placentas from women with spontaneous miscarriage (group 1) were matched with placentas from women who underwent termination (group 2). Nape-pld expression was analyzed by RT-PCR; CB1 and FAAH expression by Western blot and immunohistochemistry. Nape-pld mRNA expression was higher in group 2 than in group 1. Western blot analysis revealed higher CB1 expression and lower or absent FAAH in group 1 than in group 2. Immunohistochemistry confirmed CB1 and FAAH signals in group 1 and group 2 placentas, respectively. Human placenta contains the enzymes to synthesize AEA. Moreover, placental tissue represents a target for endocannabinoids whose activity may regulate pregnancy outcome. In particular, very low or absent FAAH and high CB1 levels correspond with spontaneous miscarriage.