Citicoline is not protective in experimental models of Huntington's disease

We have evaluated the neuroprotective effects of citicoline in relevant phenotypic models of Huntington's disease induced by either the mitochondrial inhibitor 3-nitropropionic acid or the N-methyl-d-aspartate agonist quinolinic acid, which, respectively, reproduce the metabolic defect or the excitotoxicity seen in the disease. We found that citicoline failed to reverse behavioural and histological alterations induced by both neurotoxins. In addition, citicoline did not reduce PC12 cell death induced by the expression of an N-terminal fragment of mutated Huntingtin. Altogether, our results suggest that citicoline is not a potential therapeutic agent for the treatment of Huntington's disease.     

Recurrent anterior shoulder instability. Results of the glenoid based inferior capsular shift

A total of forty consecutive patients suffering from recurrent traumatic anterior shoulder instability underwent stabilisation with a glenoid based inferior capsular shift. The patients were followed up prospectively by an independent observer (JM) using the Constant-Murley score and objective evaluation of shoulder movement and strength with an isometric dynamometer. The mean follow-up period was 50 months (range, 2 to 6.8 years). Three patients (7.5%) suffered a repeat, high energy, traumatic dislocation following an early return to sports activities. "Cybex" testing documented a minimal average loss of external rotation movement (4.4 degrees) and strength (4.3%) with the arm in neutral, which was higher with the arm at 90 degrees of abduction (i.e., 13.7 degrees and 15.6%, respectively). The deficit in internal rotation strength was similarly lower in neutral position (2%), when compared to the deficit with the arm at 90 degrees of abduction (13.5%). There was no measurable loss of internal rotation motion. Our study supports the use of a glenoid based inferior capsular shift, as there is a low recurrence rate and minimal deficit in shoulder movement and strength.     

Results of long term surgical treatment of isolated stenosis of the left descending coronary artery

The results of medical and surgical management of isolated stenosis (greater than or equal to 50%) of the left anterior descending artery were compared retrospectively in a series of 124 consecutive patients. 57 patients were managed medically (Group I). 28 (49%) presented with angina and 36 (63%) with a previous myocardial infarction. The stenosis was greater than 90% in 38 patients (67%) and was associated with severe left ventricular dysfunction in 28 patients (49%). The average ejection fraction was 53.8 +/- 2.5%. 67 patients were managed surgically (Group II): 58 (87%) presented with angina and 28 (42%) with previous myocardial infarction. The stenosis was greater than 90% in 58 patients (87%) and associated with severe left ventricular dysfunction in 19 patients (28%). The average ejection fraction was 61.7 +/- 2.4%. The average length of follow-up was 41.9 +/- 4.1 months in Group I and 46.2 +/- 3.5 months in group II. 6 patients died in Group I, 5 of a cardiac cause, compared to 4 patients (3 of a cardiac cause) in Group II, with an operative mortality of 1.6%. One patient in Group I had a new myocardial infarction compared to 6 in Group II, 3 of which (4.4%) occurred in the perioperative period. Angina regressed after therapy in 23 patients (40%) in Group I and in 48 patients (72%) in Group II (p < 0.01). Angina was unchanged or became more severe in 12 and 5 patients respectively. 34 patients (60%) on drug therapy were able to resume their professional activities as opposed to 26 (42%) in the surgical group (p < 0.05). It would therefore appear that surgery for isolated stenosis of the left anterior descending artery does not significantly reduce mortality, or prevent recurrence of myocardial infarction, but it does significantly improve anginal pain. The same conclusions are obtained when the patients are classified in different sub groups, "operable" patients or those with previous myocardial infarction or with poor left ventricular function. Finally, the surgical indications were "good" in 21 patients, symptomatic with a proximal stenosis greater than 75%, good ventricular contraction on angiography, an ejectionfraction of at least 50%, and good arterial run-off. In these cases surgery was successful with regression of anginal pain in 19 patients (90%) but complicated by secondary infarction in two of them. These results were better than those obtained in the other operated patients, in which the surgical indications were judged retrospectively to have been "inadequate". Therefore, in isolated stenosis of the left anterior descending artery, aorto-coronary bypass surgery should be reserved to patients with "good surgical indications".     

[<Superscript>18</Superscript>F]FPRGD<Subscript>2</Subscript> PET/CT imaging of integrin α<Subscript>v</Subscript>β<Subscript>3</Subscript> levels in patients with locally advanced rectal carcinoma

Purpose

Our primary objective was to determine if [¹⁸F]FPRGD₂ PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [¹⁸F]FPRGD₂ and [¹⁸F]FDG uptake, to evaluate the correlation between posttreatment [¹⁸F]FPRGD₂ uptake and tumour microvessel density (MVD) and to determine if [¹⁸F]FPRGD₂ and FDG PET/CT could predict disease-free survival.

Methods

Baseline [¹⁸F]FPRGD₂ and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63?±?8 years) with LARC before starting any therapy. A posttreatment [¹⁸F]FPRGD₂ PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 – 15 weeks) and before surgery (median interval 4 days, range 1 – 15 days).

Results

All LARC showed uptake of both [¹⁸F]FPRGD₂ (SUV_max 5.4?±?1.5, range 2.7 – 9) and FDG (SUV_max 16.5?±?8, range 7.1 – 36.5). There was a moderate positive correlation between [¹⁸F]FPRGD₂ and FDG SUV_max (Pearson’s r?=?0.49, p?=?0.0026). There was a moderate negative correlation between baseline [¹⁸F]FPRGD₂ SUV_max and the TRG (Spearman’s r?=??0.37, p?=?0.037), and a [¹⁸F]FPRGD₂ SUV_max of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p?=?0.029). In the 24 patients who underwent a posttreatment [¹⁸F]FPRGD₂ PET/CT scan the response index, calculated as [(SUV_max1 ? SUV_max2)/SUV_max1] × 100 %, was not associated with TRG. Post-treatment [¹⁸F]FPRGD₂ uptake was not correlated with tumour MVD. Neither [¹⁸F]FPRGD₂ nor FDG uptake predicted disease-free survival.

Conclusion

Baseline [¹⁸F]FPRGD₂ uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.

     

Worsening of Huntington disease phenotype in CB1 receptor knockout mice

Huntington's disease (HD) is a progressive neurodegenerative genetic disorder which leads to motor, cognitive and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. Cannabinoid CB1 receptors (CB1Rs) are particularly enriched in the striatum and previous works indicate their early loss of expression in HD, even before symptom occurrence. However, pathophysiological significance of this loss of expression remains unclear. In addition, whether specific modulation of CB1R is able to mitigate striatal neuron fate in HD remains currently controversial. In order to gain further insights on the potential role of CB1R in HD physiopathology, we evaluated the pathophysiological consequences of a genetic deletion of CB1R in the N171-82Q transgenic model and following 3-nitropropionic (3NP) intoxication. Taken together our data demonstrate that CB1R knockout (1) worsens motor performances in N171-82Q mice and (2) increases mouse susceptibility to 3NP. These results suggest that functional changes in CB1R may contribute to the physiopathological development of HD.     

Congenital absence of the circumflex artery. Association with an infarction without coronary disease]

A 31 year old man had a congenitally absent circumflex coronary artery, one of the least described of all the congenital abnormalities of the coronary arteries. Before confirmation of the diagnosis, an ectopie circumflex artery was excluded by the two angiographical signs observed by Page and by non-selective coronary arteriography. This abnormality was thought to have played a role in myocardial infarction in this young patient without coronary risk factors and with no obvious coronary artery narrowing on coronary arteriography.     

Interventricular septum. Angiographic and echocardiographic correlations

The diastolic thickness of the interventricular septum was measured by echocardiography and by biventricular angiography in 48 patients (40 male, 8 female) with age ranging between 15 and 67 years (average 44.4 years). These patients were classified in four groups according to clinical and paraclinical parameters:--normal subjects (29 cases),--patients with concentric hypertrophy (5 cases),--patients with asymmetrical septal hypertrophy without obstruction (4 cases),--patients with hypertrophic cardiomyopathy with obstruction under basal conditions or under stress (10 cases). Biventricular cineangiography was performed in 70 degrees left anterior oblique projection after measuring the intracavitary pressures. Analysis was performed by projecting the film and reproducing one or several diastolic frames on paper. Septal thickness was measured at the two levels suggested by Redwood. The septum was then divided into 5 parts and the thickness measured at the corresponding 4 levels. The values obtained were then corrected for magnification artefact. Qualitative comparison of the results obtained by echocardiography and angiocardiography showed a good correlation in 35 cases (73%) and less significant correlations in the other 13 cases (27%). The poorest correlations were observed in the groups of patients with concentric or asymmetrical hypertrophy without obstruction. Of these 13 cases, angiography confirmed the clinical diagnosis in 6 cases. In the remaining 2 cases, echocardiography and angiocardiography gave divergent diagnoses which also differed from the clinical diagnosis. The quantitative correlations between the echocardiographical and angiocardiographic measurements of diastolic septal thickness were quite satisfactory in most patients. The correlation improved when the echocardiographical measurement was compared to an average of the 4 angiographical measurements; (R = 0,74; p < 0.001). The correlation was poorer in groups 2 and 3 in patients with concentric or asymmetrical hypertrophy without obstruction. The disadvantages and limitations of these two methods are discussed. Possible ambiguity in the identification of segments of the septum measured by the two methods may be a significant factor especially in cases of asymmetrical hypertrophy.     

Ibopamine in very severe congestive heart failure: Pilot haemodynamic invasive assessment

The acute effects of ibopamine, a new, orally active dopaminergic agent, were assessed invasively in 8 patients with congestive heart failure (NYHA Class IV). The cardiac Index increased (P less than 0.01) and preload and afterload decreased (P less than 0.05) after a single mean dose of ibopamine 1.4 mg/kg. The peak effect occurred after 1 to 3 h and activity was still demonstrable after 4 to 6 h. There was no change in blood pressure, heart rate or rhythm. No clinical evidence of cardiac toxicity or side effects was noted. Oral ibopamine shows promise in the treatment of congestive heart failure, but more extensive studies after chronic treatment are desirable.