Trace amine metabolism in Parkinson's disease: Low circulating levels of octopamine in early disease stages

Recent evidence suggests that trace amines such as tyramine and octopamine, alternative products of tyrosine metabolism (an aminoacid parent of dopamine and noradrenaline), play a role in the homeostasis of the extrapyramidal system. However, the relevance of these trace amines in the pathogenesis of Parkinson's disease is still largely unknown. Here, we assessed the plasma levels of octopamine and noradrenaline in three sub-groups of PD patients, namely de novo, non-fluctuating and fluctuating patients, versus age-matched control subjects. We show that octopamine is detectable in plasma of all subjects, the mean levels of which are significantly lower in PD patients, including de novo patients, when compared to controls (p < 0.001). Unlike this, no changes in plasmatic noradrenaline levels were found in the de novo patients, but only in plasma of fluctuating and non-fluctuating PD patients. These findings raise the possibility that Parkinson's disease is firstly characterized by abnormalities of tyrosine decarboxylase, rather than tyrosine hydroxylase, enzyme activity. Given the role of this enzyme in the production of trace amines, circulating octopamine levels may hold promise as a biomarker of early Parkinson's disease.     

Laparoscopic sacrocolpopexy with two separate meshes along the anterior and posterior vaginal walls for multicompartment pelvic organ prolapse

STUDY OBJECTIVE: To assess the feasibility and results of laparoscopic sacrocolpopexy (LSC) with two separate meshes along the anterior and posterior vaginal walls in correcting multicompartment pelvic organ prolapse (POP). DESIGN: Prospective study (Canadian Task Force classification I). SETTING: Tertiary care university-affiliated teaching hospital. PATIENTS: Forty-six consecutive women with radiologic diagnosis of multicompartment POP with or without genuine stress urinary incontinence and no history of surgery for either disorder. INTERVENTION: LSC with or without laparoscopic Burch colposuspension or tension-free vaginal tape procedure. MEASUREMENTS AND MAIN RESULTS: LSC was performed in 89% of patients. Mean operating and hospitalization times were 171 +/- 37 minutes and 4.0 +/- 2.1 days, respectively. Intraoperative complications were 7% of bladder injuries successfully treated by laparoscopic suture. The success rate for POP was 83%. The main recurrence was rectocele (12%), which occurred only among women undergoing LSC plus laparoscopic Burch colposuspension (P = 0.036). The LSC was effective in treating symptoms in 95% of women. Because of excessive mesh tension, one patient (2%) developed obstructed defecation, and two (5%) had de novo urinary incontinence. In no patient did occlusion or mesh infection and/or erosion in adjacent organs occur. CONCLUSION: LSC appears to be feasible and effective in treatment of multicompartment POP. Performing concomitant Burch colposuspension significantly enhances the risk of rectocele recurrence or development.     

Clinical management of non palpable breast lesions: experience about a series of 176 consecutive cases

OBJECTIVE: To propose a rational attitude to treat infraclinic breast lesions about a 176-case retrospective analysis. PATIENTS AND METHODS: Between January and December 2000, 176 patients were addressed for an infraclinic breast lesion. The epidemiologic and mammographic data, diagnostic management and histological results were collected. RESULTS: Patients were addressed for an ACR 2 lesion in 0.8% of cases, ACR 3: 34.8%, ACR 4: 43.2% and ACR 5: 21.2%. One hundred and sixteen patients underwent a stereotactic macrobiopsy: 55 Advanced Breast Biopsy Instrumentation (ABBI), 61 Minimal Invasive Breast Biopsy (MIBB). Histologically, 59.5% were benign, 33.6% malignant, 2.6% borderline and 4.3% suspicious or non contributive. Forty-two patients underwent an open surgical biopsy. Histologically 56.1% were benign, 41.5% malignant and 2.4% borderline. Eighteen patients were controlled by mammography. Among ACR 3s there were 90% of benign lesions and 46% of malignancy in ACR 4s. Patients with malignant, borderline or suspicious result in stereotactic biopsy, underwent one-time surgery in 97% vs 55% in surgical biopsy (P < 0.0001). DISCUSSION AND CONCLUSION: Infraclinic breast lesions must be radiologically classified with the ACR classification. Stereotactic macrobiopsies are reserved for ACR 4 and ACR 5 lesions. Because of their reliability, practice of macrobiopsies avoids surgery in about 50% of ACR 4 lesions which correspond to benign lesions. When the result is malignant, it allows most of times surgical procedure one-time.     

Migraine prevalence in eating disorders and pathophysiological correlations

Acute hemorrhagic leukoencephalitis (AHL) is a rare demyelinating disease mainly affecting children, characterized by acute onset, progressive course and high mortality. A 62-year-old man was admitted to our Unit for diplopia and ataxia ensuing 2 weeks after the onset of pneumonia. MRI T2-weighted images showed signal hyperintensities in the brainstem. Antibodies against Mycoplasma Pneumoniae and cold agglutinins were found. Two weeks later the patient had a worsening of his conditions: he developed left hemiplegia with motor focal seizures and the day after he was deeply comatose (GCS = 4). A second MRI scan showed extensive hyperintensities involving the whole right hemisphere white matter with a small parietal hemorrhagic area. The clinical and neuroimaging features suggested the diagnosis of AHL, Aciclovir in association with steroid therapy were administered and then plasmapheresis was started. After 30 days of coma, the patient gradually reacquired consciousness and motor functions; anyway a left hemiplegia persisted.     

Neoadjuvant chemotherapy with vincristine, bleomycin and methotrexate combined with radiotherapy in advanced head and neck squamous cell carcinoma

From September 1980 to August 1981, 25 patients with advanced head and neck squamous cell carcinoma were treated at the Centro Oncologico, Trento, by a chemo-radiotherapeutic combination. The treatment protocol consisted of 4-6 courses of VBM (vincristine, bleomycin and methotrexate) followed by conventional radiotherapy (65 Gy). Only to VBM responders (15 patients) were administered 10 cycles of vincristine-methotrexate. At the end of induction chemotherapy an overall response of 60% (12% complete, 48% partial) was obtained. At the end of radiotherapy the responses were 52.5% complete and 35.5% partial, for an overall response of 88%. The overall survival at 60 months was 8%. This combined approach, in spite of the satisfactory immediate local response rate, does not offer advantages for survival in comparison to conventional treatment modalities.     

Influence of dietary taurine on vitamin D absorption

To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25–hydroxyvita-min D3 (250HD3) and 1,25–dihydroxyvitamin D3 (1,250H2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 250HD3 and 1,250H2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged.     

Study of tyrosine metabolism in eating disorders. Possible correlation with migraine

In order to understand the possible role of tyrosine metabolism and in particular that of elusive amines in the pathogenesis of eating disorders (ED), we measured the plasma levels of dopamine, noradrenaline, tyramine (Tyr) and octopamine (Oct) in a large group of anorexic and bulimic patients. In comparison to the control group, the levels of nordrenaline were significantly lower and those of dopamine and Tyr higher in the ED patients. The plasma levels of Oct were in the same range in both subject groups. However when comparing the bulimic vs. the anorexic group, the Oct levels were significantly lower in the anorexic group, whereas those of Tyr were significantly higher in the bulimic patients, suggesting that different activation in the metabolism of elusive amines may underlie the shift from the anorexic into the bulimic state. These biochemical findings raise the possibility that abnormalities of the limbic and hypothalamic circuitries play a role in the pathogenesis of ED. In addition, the very high prevalence of migraine (>75%) in our group of ED sufferers, and the biochemical profile(s) reported in migraine, which appear similar to that found in ED patients, suggest that migraine constitutes a risk factor for the occurrence of ED in young females.     

"Method-specific" stability of serum C-peptide in a multicenter clinical study

A Central laboratory that participates in multicenter clinical studies must consider and study the parameters that condition the in vitro stability of the analytes. We evaluated the effect of temperature on serum C-peptide storage during transport from clinical research centers to the Central laboratory. In particular, the stability for storage lengths from 0 to 24-48 hours at temperatures of between -20 degrees C and +37 degrees C were studied: the C-peptide assay was performed by means of a chemiluminescence and a RIA method. The tests confirmed that sample freezing is the gold standard for accurate determination of serum C-peptide and that storage at 37 degrees C may decrease the analyte levels. Instead, C-peptide stability at 2-8 degrees C appeared "method-specific"; while no apparent alteration was obtained with the chemiluminescence method up to 24 hours of storage, the RIA showed an early slight increase in C-peptide that is proportionate to storage time. Our work highlights that before starting up a multicenter clinical study it is always necessary to optimize and standardize biological sample storage and transport conditions to guarantee a high quality sample for analysis. Beyond this, it is even very useful to check the reliability of technical and instrumental resources that the Central laboratory will use during the study because molecular alterations of the analytes due to variable storage conditions can cause misleading results.