Is there evidence of bradykinesia in essential tremor?

BACKGROUND AND PURPOSE: Essential tremor (ET) is a movement disorder primarily characterized by upper limb postural and kinetic tremor. Although still under-investigated, bradykinesia may be part of the phenotypic spectrum of ET. The aim was to evaluate bradykinesia features in ET through clinical examination and kinematic analysis of repetitive finger movements. Data collected in ET patients were compared with those recorded in Parkinson's disease patients and healthy controls. METHODS: Overall, 258 subjects participated in the study (90 ET patients, 84 Parkinson's disease patients and 84 healthy controls). Repetitive finger tapping was kinematically recorded using a motion analysis system. Movement velocity, amplitude and decrement (sequence effect) were measured. The three groups were first compared by one-way analysis of variance. A cluster analysis was also performed to better address the data variability observed in ET patients. Possible relationships between kinematic and clinical data were assessed in ET patients. RESULTS: Essential tremor patients were slower than healthy controls. Movement slowness in ET did not correlate with postural or kinetic tremor severity. It was also found that movement slowness in ET was not associated with a sequence effect, which instead is a common feature in Parkinson's disease. Cluster analysis showed that a proportion of ET patients may have movement abnormalities similar to those observed in Parkinson's disease. CONCLUSIONS: Movement slowness without sequence effect is a common feature in ET patients. The present findings are relevant when interpreted in the context of the new tremor classification system and in the development of a more accurate bradykinesia definition.

Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery.

BACKGROUND: Drugs that act on the platelet P2Y12 receptor are responsible for postoperative bleeding in cardiac surgery. However, protease-activated receptor (PAR) that reacts to thrombin stimulation might still be active in patients treated with P2Y12 inhibitors. Preoperative platelet function testing could possibly guide the timing of surgery. We investigated the association between P2Y12 receptor and PAR inhibition and bleeding after cardiac surgery. METHODS: A retrospective cohort study of 361 patients undergoing cardiac surgery and treated with P2Y12 anti-platelet agents was undertaken. All patients received a preoperative multiplate electrode aggregometry testing of platelet P2Y12 receptor activity (ADPtest) and PAR reactivity with thrombin receptor-activating peptide (TRAP) stimulation. ADPtest and TRAPtest data measured before surgery were analysed for association with postoperative bleeding (ml per 12 h) and severe postoperative bleeding. RESULTS: Both the ADPtest and the TRAPtest were significantly (P=0.001) associated with postoperative bleeding. A threshold of 22 U for the ADPtest yielded a negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 20%, and a threshold of 75 U for the TRAPtest yielded an NPV of 95% and a PPV of 23%. In the subgroup of patients with ADPtest <22 U, TRAPtest ≥75 U was not associated with severe bleeding (NPV of 100% and PPV of 37%). CONCLUSIONS: In patients taking P2Y12 receptor inhibitors, residual platelet reactivity to thrombin stimulation limits the risk of severe postoperative bleeding.

Physical self-perception and motor performance in normal-weight, overweight and obese children.

The aim of this study was to examine the relationships among physical self-perception, body image and motor performance in Italian middle school students. Two hundred and sixty children were categorized into normal-weight (n=103), overweight (n=86) or obese (n=71) groups. Perceived coordination, body fat and sports competence were assessed using the Physical Self-Description Questionnaire, while body image was measured using Collins' Child Figure Drawings. Individuals' perceptions of strength, speed and agility were assessed using the Perceived Physical Ability Scale. Tests involving the standing long jump, 2 kg medicine-ball throw, 10 × 5 m shuttle-run and 20 and 30 m sprints were also administered. Girls, when compared with boys, and overweight and obese participants, when compared with normal-weight peers, reported lower perceived and actual physical competence, higher perceived body fat and greater body dissatisfaction. Body dissatisfaction mediated all the associations between body mass index (BMI) and the different aspects of physical self-perception in boys, but not in girls. The same pattern of results was found for physical self-perception as a mediator of the relationship between BMI and body dissatisfaction. In conclusion, obesity proved to have adverse effects on both motor performance and physical self-perception.

Preoperative shift from glibenclamide to insulin is cardioprotective in diabetic patients undergoing coronary artery bypass surgery.

AIM: The cardioprotective effects afforded by volatile anesthetics, i.e. isoflurane, during heart surgery may be due to preconditioning of the myocardium through the activation of KATP channels. The aims of this study were to establish whether glibenclamide prevents the isoflurane-induced cardioprotection in diabetic patients undergoing coronary surgery (CABG) and whether this cardioprotective effect can be restored by preoperative shift from glibenclamide to insulin therapy. METHODS: We enrolled 60 patients undergoing CABG. Twenty consecutive non-diabetic patients were randomized to receive conventional anesthesia (CA) or conventional anesthesia plus isoflurane (ISO) (added to the inspired oxygen before starting cardiopulmonary bypass); 40 consecutive diabetic patients in chronic treatment with oral glibenclamide were randomized to conventional anesthesia (G-CA), conventional anesthesia plus isoflurane (G-ISO), conventional anesthesia after shifting to insulin (I-CA) or conventional anesthesia plus isoflurane after shifting to insulin (I-ISO). Serum levels of cardiac troponin I (CTnI) and CK-MB, as markers of ischemic injury, were obtained 1, 24, 48 and 96 hours, postoperatively. RESULTS: Postoperative peak levels of CTnI and CK-MB were lower in ISO than in CA (0.5+/-0.3 vs 2.8+/-2.2 ng/ml, p<0.05 and 61+/-27 vs 79+/-28 U/L, p<0.05, respectively), as well as in I-CA and I-ISO than G-CA and G-ISO groups (0.5+/-0.7 and 0.7+/-0.9 vs 3.5+/-3 and 2.7+/-2.5 ng/ml, p<0.05; 47+/-7 and 41+/-5 vs 85+/-28 and 50+/-23 U/L, p<0.05, respectively). No significant differences were detected in postoperative hemodynamic variables or in-hospital outcome. CONCLUSION: This prospective randomized study shows a cardioprotective effect of preoperative administration of isoflurane during CABG. Such an effect is prevented by glibenclamide, but can be restored in diabetic patients by preoperative shift from glibenclamide to insulin.

[Videolaparoscopic adrenalectomy in an unusual case of adrenal mycetoma]. / La surrenectomia video-laparoscopica in un raro caso di micetoma del surrene.

The authors report a rare case of mycetoma of the adrenal gland. Mycetoma is a chronic, localized, non-contagious infection of cutaneous and subcutaneous tissue characterized by tumefaction, aggregates of aetiological agents (Actinomyces or true fungi). Sometimes an unusual site (other tissues or organs) is described in the literature, but to date no cases of adrenal gland mycetoma have been reported. The treatment of choice is surgical with associated penicillin and/or antifungal drugs. In the case reported surgical treatment is performed with a laparoscopic approach. This technique constitutes the gold standard in cases of benign neoplasms of the adrenal gland and incidentalomas. This therapeutic choice is open to criticism if a malignant neoplasm is suspected.

A new aortic Dacron conduit for surgical treatment of aortic root pathology.

BACKGROUND: This article describes a new aortic Dacron conduit that has been designed for use in all types of surgery of the aortic root. Its use is aimed at facilitating the surgical procedure and obtaining a natural anatomical configuration of the aortic root. METHODS: The modified Dacron conduit is obtained by adding a smaller piece of Dacron tube that is resilient in the horizontal plane to one end of a standard Dacron conduit. Upon implantation, this small piece of Dacron conduit will stretch in the horizontal plane creating pseudosinuses and a new sinotubular junction. This modified conduit has been used in 4 cases for a Bentall operation in association with a mechanical or a biological valve, in 4 cases in a Yacoub type of valve sparing procedure and in 1 case in a David type I of valve sparing procedure. All patients had aortic root aneurysm with severe aortic regurgitation. There were 6 males and 3 females with a mean age of 61 +/- 16 years. In most cases a 28 mm Dacron conduit was used. RESULTS: All surgery was carried out without mortality or morbidity. The creation of pseudosinuses was confirmed intraoperatively by visual inspection. Transesophageal echocardiography in patients who had undergone the Bentall operation showed a normally functioning valve prosthesis with a suitably shaped aortic root. In patients who had undergone the valve sparing procedures it showed a competent aortic valve, the creation of pseudosinuses of normal shape and depth, and the presence of a well defined sinotubular junction. Angiography confirmed that the prosthetic aortic root perfectly resembled the normal root anatomy. CONCLUSIONS: This modified new aortic root conduit appears to perfectly reproduce a normal root anatomy without the need of modifying the original techniques.

16(R)-hydroxy-5,8,11,14-eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes.

Intact human polymorphonuclear leukocytes (PMNL) incubated with substimulatory amounts of arachidonic acid in the absence of a calcium ionophore formed four metabolites that were isolated by reverse-phase HPLC and characterized structurally by GC/MS. A major metabolite eluting as the most abundant peak of radioactivity lacked UV chromophores above 215 nm, and its formation was sensitive to 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF525A) but not 3-amino-1-[m(trifluoromethyl)phenyl]-2-pyrazoline (BW755C), suggesting that it was likely to be a product of cytochrome P450. The GC/MS analysis revealed the presence of two components: 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) and 16-hydroxy-5,8,11,14-eicosatetraenoic acid (16-HETE) in an approximate ratio of 4:1. The minor metabolites were identified as 15-HETE and 5-HETE. Although 20-HETE has been observed previously as a product of arachidonic acid metabolism in PMNL, the occurrence of 16-HETE was a novel finding. The stereochemistry of the hydroxyl group in PMNL-derived 16-HETE was established by analysis of 1-pentafluorobenzyl-16-naphthoyl derivatives on a chiral-phase chromatographic column and comparison with authentic synthetic stereoisomers. The PMNL-derived radioactive metabolite co-eluted with the synthetic 16(R)-HETE stereoisomer. Analysis of the total lipid extracts from intact PMNL followed by mild alkaline hydrolysis resulted in detectable amounts of 16-HETE (108+/-26 pg/10(8) cells) and 20-HETE (341+/-69 pg/10(8) cells), which suggested that these HETEs were formed from endogenous arachidonic acid and esterified within PMNL lipids. Thus, in contrast to calcium ionophore-stimulated neutrophils that generate large amounts of 5-lipoxygenase products, the intact PMNL generate 20-HETE and 16(R)-HETE via a cytochrome P450 omega- and omega-4 oxygenase(s).

Brain chirps: spectrographic signatures of epileptic seizures.

OBJECTIVE: A chirp is a brief signal within which the frequency content changes rapidly. Spectrographic chirps are found in signals produced from many biological and physical phenomena. In radar and sonar engineering, signals with chirps are used to localize direction and range to the signal source. Although characteristic frequency changes during epileptic seizures have long been observed, the correlation with chirps and chirp technology seems never to have been made. METHODS: We analyzed 19404 s (1870 s of which were from 43 seizures) of intracranially (subdural and depth electrode) recorded digital EEG from 6 patients for the presence of spectral chirps. Matched filters were constructed from methods in routine use in non-medical signal processing applications. RESULTS: We found that chirps are very sensitive detectors of seizures (83%), and highly specific as markers (no false positive detections). The feasibility of using spectral chirps as matched filters was demonstrated. CONCLUSIONS: Chirps are highly specific and sensitive spectrographic signatures of epileptic seizure activity. In addition, chirps may serve as templates for matched filter design to detect seizures, and as such, can demonstrate localization and propagation of seizures from an epileptic focus.

Independent value of tumor size and DNA ploidy for the prediction of disease progression in patients with organ-confined renal cell carcinoma.

BACKGROUND: Greater than 20% of patients with apparently localized renal cell carcinoma (RCC) present with disease progression after surgery. The objective of the current study was to improve the ability of clinicians to predict prognosis in patients with localized RCC. METHODS: The authors studied 154 patients with organ-confined RCC classified as pT1 to pT2-pN0-M0 who underwent radical nephrectomy. Follow-up ranged from 24-128 months (median, 72 months). Several morphologic parameters of the tumor were considered. DNA content was analyzed by flow cytometry and tumor size was determined from the surgical specimen. A Cox proportional hazards regression model was used to identify significant independent prognostic factors for disease progression. RESULTS: At 5 and 10 years of follow-up, disease free survival was found to be 87% and 86%, respectively. Univariate analysis revealed that DNA content, Furhman grade, and tumor size had a statistically significant predictive value for disease progression, whereas, with regard to grade, the difference was significant only between patients with Grade 3 tumors and all other patients with Grade 1-2 tumors (P < 0. 0001). Although DNA content was found to correlate with tumor size (P < 0.0001), multivariate analysis showed that these were the only significant independent predictors of disease progression. The sum of DNA content and tumor size therefore was considered to distinguish separate risk groups. For a patient with diploid RCC, the risk of progression increased from 4% if the tumor size was 3 cm to 43% if the tumor size was 10 cm. For a patient with nondiploid RCC, this risk was 32% if the tumor size was 3 cm, increasing to 99% for tumors measuring 10 cm. CONCLUSIONS: Stratification of organ-confined RCC according to tumor size and DNA content could possibly provide more information that could be useful in the selection of individuals with significantly different risks of disease progression.

[Laparoscopic surgical treatment of cholecysto-choledochal calculi. A single step solution]. / Trattamento chirurgico laparoscopico della calcolosi colecisto-coledocica. La soluzione in un unico atto.

The laparoscopic era has created a new basis for the management of choledocholithiasis. Many surgeons now regard laparoscopic cholecystectomy and exploration of the common bile duct as the "gold standard". The main advantages of single-stage treatment consist in a significantly shorter hospital stay, very low complication rates and a reduction of average hospital costs. Among 601 cases of cholelithiasis treated over the period from 1994 to 1999, we report 73 cases of common-bile-duct stones. Surgical sphincterotomy was performed in 20 cases and endoscopic sphincterotomy in 24; only in 7 cases was choledochotomy and/or hepaticojejunostomy (3 cases) performed for critical situations. Twenty-two cases of cholelithiasis were treated by laparoscopic cholecystectomy and exploration of the common bile duct. Stone extraction was obtained with a balloon catheter or Dormia basket via a choledochotomy. Surgery was completed by suturing, cholangiography and the placement of sub-hepatic drainages. No mortality or long-term complications were recorded with the laparoscopic procedure; only two immediate complications were reported, both of which were biliary leakages (9%) that resolved spontaneously. With the other procedures, high rates of mortality, morbidity, hospital admissions and technical failure were registered. We regard laparoscopic exploration of the common bile duct as the treatment of choice for bile-duct stones when combined with cholecystectomy. We reserve ERCP plus endoscopic sphincterotomy only for common-bile-duct stones alone, without a gallbladder or gallstones. Open surgery is performed in particular situations such as Mirizzi's syndrome or when other procedures have failed to yield satisfactory results.

Intermittent androgen deprivation (IAD) in patients with localized prostate cancer and a biochemical progression after radical prostatectomy.

BACKGROUND: To analyze the modifications in serum PSA levels during IAD in patients with an initial PSA progression after radical retropubic prostatectomy (RRP). METHODS: Between February 1994 and May 1996, 34 consecutive patients with an initial PSA progression (> 0.4 ng/ml) after RRP were selected. All men had localized adenocarcinoma of the prostate, stage pT2 pN0 M0. Patients were offered IAD when PSA progressed over 0.4 ng/ml. The initial treatment period with complete androgen deprivation (CAD) lasted 24 weeks in all cases. After, an acceptable nadir PSA level was considered to be a value < or = 0.4 ng/ml. CAD was then with held until serum PSA increased to a value over 0.4 ng/ml. RESULTS: Follow-up ranges from 144 to 228 weeks. The median time for the first 5 treatment cycles was 32, 24, 28, 32 and 32 weeks respectively, with a median time "off" therapy that increased from 8 weeks (first cycle) to 22 weeks (fifth cycle). The median nadir PSA value during "on" treatment period was 0.20 ng/ml in all 5 cycles. So far, in none of the patients did a serum PSA fail to decrease during "on" treatment period. CONCLUSIONS: We suggest that IAD may be an effective therapy in patients with an initial PSA progression after RRP. However, large prospective studies are needed to confirm these results and to better understand the meaning of PSA variations.

Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.

BACKGROUND: Experimental studies indicate that isoflurane, a commonly used volatile anesthetic, mimics the cardioprotective effects of ischemic preconditioning, probably through ATP-sensitive K+ (KATP) channel activation. The aim of this study was to evaluate the impact of isoflurane during coronary bypass surgery (CABG) on troponin I release. MATERIAL AND METHODS: Forty consecutive patients with chronic stable angina and multivessel disease undergoing isolated CABG were randomized to a control (16 men and 4 women, aged 51 to 73 years, mean 62) or isoflurane (15 men and 5 women, aged 51 to 77 years, mean 65) group before aortic cross-clamping and cardioplegia. Serum levels of troponin I and creatine kinase (CK)-MB, as markers of ischemic injury, were obtained at 24 hours after CABG. Regional wall motion score and left ventricular ejection fraction (LVEF) at transthoracic echocardiography were assessed 5 days postoperatively. Comparisons between groups were performed in the entire population and, subsequently, in those patients with preoperative LVEF < 50%. RESULTS: There were no significant differences between isoflurane-treated patients and controls in cross-clamp time (49 +/- 14 vs 51 +/- 13 min, p = ns), peak values of troponin I (0.9 +/- 0.7 vs 1.4 +/- 1.3 ng/ml, p = ns) and CK-MB (62 +/- 27 vs 64 +/- 27 U/l, p = ns), or postoperative echocardiographic score (26 +/- 7 vs 22 +/- 5, p = ns) and LVEF (53 +/- 10 vs 55 +/- 7%, p = ns). When the comparisons were restricted to those patients with preoperative LVEF < 50%, at 24 hours the isoflurane-treated patients exhibited a smaller release of troponin I and of CK-MB than controls (1.1 +/- 0.7 vs 2.3 +/- 1.3 ng/ml, p = 0.03, and 39 +/- 10 vs 57 +/- 22 U/l, p = 0.04, respectively). CONCLUSIONS: Isoflurane reduces myocardial injury in patients with impaired left ventricular function undergoing CABG; thus, it can be safely used as an additional cardioprotective tool during routine CABG in high-risk patients with poor left ventricular function.

Hormone-refractory prostate cancer? Anti-androgen withdrawal and intermittent hormone therapy.

OBJECTIVE: To separate hormone-dependent from hormonally relapsed prostate cancers, a D3 category has been proposed. The term has become synonymous with a hormone-refractory state with the implication that any further hormonal treatment would not be beneficial. In this review we examine some data on androgen receptor expression, anti-androgen withdrawal syndrome and intermittent androgen deprivation (IAD) in patients with advanced prostate cancer. MATERIALS: The literature on the mechanism of the withdrawal phenomenon in patients with prostate cancer submitted to hormone therapy was reviewed. Experimental and clinical data are reported. RESULTS: The progression of prostate cancer in patients treated with combined androgen blockade (CAB) is associated with the activation of previously androgen-repressed genes, some of which may code for autocrine and paracrine growth factors that substitute for androgens in maintaining the viability of the tumorigenic stem cells. If androgens are replaced before progression begins, the surviving stem cells should give rise to an androgen-dependent tumor, which would be amenable to retreatment by CAB. This theory provides the rationale for intermittent androgen deprivation. We suggest that IAD could be more effective in patients with initial prostate-specific antigen (PSA) progression after radical prostatectomy. CONCLUSIONS: Response to withdrawal therapies or second-line treatments is an example of a "hormonal" therapy that may benefit a proportion of patients with hormone-refractory disease, suggesting that the tumor is still androgen-dependent. Whether IAD enhances progression-free survival or overall survival must be verified in randomized clinical trials. Until further studies have been completed, the therapeutic concept of IAD should be treated as experimental.

[Limitations on the interpretation of prostate-specific antigen serum levels]. / Limiti nell'interpretazione dei livelli sierici dell'antigene specifico prostatico (PSA).

Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.

Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?

The efficacy of radical prostatectomy on localized prostate cancer is well documented. However if a high risk for patients suffering from prostate cancer and effectiveness of treatment would be documented, the advantage of the therapy on the natural history of the disease must be demonstrated. Johansson et al. analyzed the natural history of 223 untreated localized prostate cancer with a mean follow up of 123 months. Only 8.5% of the patients died of prostate cancer. The 10 year disease specific survival rate was 86.8%. The progression free survival rate was 53.1%. Zincke et al. reported that the disease specific survival of the T1 T2 submitted to radical prostatectomy at 15 years was 93% and the survival free of disease was 70%. Our data on localized prostate cancer submitted to radical prostatectomy showed that the disease specific survival and the progression free survival after 5 years of follow-up were 99% and 85.7% respectively. Fleming, focusing on life expectancy, demonstrated that radical prostatectomy provides some benefit compared with watchful waiting for patients younger than 70 years. The greatest marginal benefits of treatment arise when we assume higher metastatic rates and higher treatment efficacy. In fact in this case, radical prostatectomy offers 3.5 years of improvement in quality of life adjusted survival in younger patients with moderately or poorly differentiated tumors. Radical prostatectomy can particularly benefit selected groups of patients with localized prostate cancer. The grade of differentiation has been shown to be the most powerful predictor in several series. DNA ploidy and tumor volume may be other reliable prognostic factors. Among all the parameters considered, the two with greatest effect in determining the outcome of treatment compared to watchful waiting were the rate of progression to metastatic disease in untreated patients and the estimated efficacy of treatment in reducing the metastatic rate.