Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Validating screening instruments for neuroepidemiologic surveys: experience in Sicily. Sicilian Neuro-Epidemiologic Study (SNES) Group.

In a hospital setting in Sicily, we assessed a screening instrument developed for a prevalence survey of parkinsonism, peripheral neuropathies, stroke, and epilepsy. The subjects consisted of (1) hospital patients with any of the above-mentioned diseases, to investigate sensitivity; and (2) hospital visitors free of all these diseases, to investigate specificity. The standard for comparison was a clinical evaluation based on specified criteria. Trained interviewers administered the screening instrument, asking subjects to answer symptom questions and to perform simple physical tasks. For the questions and tasks together, the sensitivity estimates were 100% for parkinsonism (n = 21), 96% for peripheral neuropathies (n = 22), 96% for stroke (n = 22), and 96% for epilepsy (n = 22), while the specificity estimate was 86% (n = 21). Analogous estimates were computed for the set of questions, for the set of tasks, and for each question and task individually. Despite limitations in our approach, we concluded that the screening instrument would be adequate for its intended use.     

Clinical Pathological Findings in an Owl (Athene noctua) with Microfilaraemia in Italy

We report the first case of microfilaria infection in a free‐flying owl Athene noctua in Italy. A macroparasite, about 10.1‐mm long, was observed in the right chamber of the heart. On microscopic examination microfilariae were seen in liver, kidney, myocardium and lungs, although no cellular reaction was present in association with the parasites in any of these tissues. Because of the low pathogenicity of this parasite, infection with microfilaria may be not harmful in wild owls.     

Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition

We studied the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of interhemispheric connections in 13 right-handed healthy volunteers. TMS was performed using figure-eight coils, and surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor cortex (M1) followed by a test stimulus to the opposite M1 was used to study the interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles. After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049) and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre-RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly different. We conclude that 1-Hz rTMS reduces IHI in both directions but is predominantly from the stimulated to the unstimulated hemisphere. Low-frequency rTMS may be used to modulate the excitability of IHI circuits. Treatment protocols using low-frequency rTMS to reduce cortical excitability in neurological and psychiatric conditions need to take into account their effects on IHI.     

TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal,intermediate, and premutation alleles

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.     

Resting ECG is modified after oophorectomy and regresses with estrogen replacement therapy in premenopausal women

OBJECTIVE: To assess the effects of bilateral oophorectomy on the resting ECG and whether they regress with estrogen replacement therapy. STUDY DESIGN: Twenty-six premenopausal and 15 postmenopausal women were enrolled in the present study. All women had undergone hysterectomy and bilateral ovariectomy. All women underwent 12-lead ECG on admission to hospital. A second ECG was recorded 20-25 days after surgery. After this second ECG, premenopausal women were randomly divided into two groups. The women of Group A (n=14) received transdermal ethinyl estradiol (EE). The women of Group B (n=12) did not receive any therapy. A third ECG was performed in both groups 30-35 days after randomization. RESULTS: Bilateral oophorectomy did not induce any significant modifications in the ECG parameters of the postmenopausal women whereas in the premenopausal women, we observed a significant increment in mean duration of the T wave, a significant decrease in its amplitude and significant reduction in ST depression in V2, V3, V4 and V5. The third ECG showed regression of the ECG modifications in Group A. In the women of Group B, the second and third ECGs were not substantially different, but there were statistically significant differences between the first and third ECGs. CONCLUSIONS: The results of the present study show that ovariectomy induces significant though not clinically evident modifications in resting ECG. These ECG changes are probably due to the sudden reduction in sex hormone plasma levels after ovariectomy. Administration of estradiol induced regression of the ECG modifications.     

Parkinson disease survival: a population-based study

OBJECTIVE: To evaluate whether the survival of patients with Parkinson disease (PD) is shorter than that of the general population. DESIGN: Survival was investigated in a cohort of patients with PD previously identified during a population-based prevalence study (prevalence day, November 1, 1987, reference follow-up date, October 31, 1995). The survival of patients with PD was compared with that of a control sample randomly selected from the same population (2 controls for each case, matched for age, sex, and study municipality). The causes of death in the 2 groups were also compared. Both univariate and multivariate survival analyses were performed to investigate the association with disease-related variables. SETTING: A door-to-door 2-phase prevalence survey performed in 3 Sicilian municipalities. PATIENTS: Fifty-nine patients with PD and 118 controls. RESULTS: Patients with PD showed a high risk of death (relative risk, 2.3; 95% confidence interval, 1.60-3.39). Greater age at November 1, 1987, high Hoehn-Yahr score, and lack of levodopa therapy were associated with a lower survival on univariate analysis. Multivariate analysis confirmed the association between shorter survival among patients with PD and greater age on November 1, 1987. One-way analysis of variance indicated a different effect of levodopa therapy according to age. Multivariate analysis did not confirm this finding. Pneumonia was the cause of death most frequently associated with PD. CONCLUSION: This study indicates that patients with PD have a shorter survival time than the general population.