Mitochondrial and redox dysfunction in post-menopause as risk factor of neurodegenerative disease: a pilot study testing the role of a validated Japanese functional food.

During the menopause women may experience increased oxidative stress and decreased antioxidant capacity and, together with the decline of neurosteroids, this represents a risk factor for Alzheimer's disease. The aim of the present study was to test a functional food (FPP-ORI, Osato Research Institute, Gifu, Japan) on redox and mitochondrial efficiency in post-menopausal women. The study population consisting of 69 untreated post-menopausal women were given supplements as follows: Group A was given a multivitamin (MV) 1c 2 times a day, and group B was given FPP 4.5 g 2 times a day. Group C consisted of 23 fertile premenopausal women as the control group. The tests carried out on entry, and at 3 and 6 months were erythrocyte redox parameters, plasma oxidated proteins, brain-derived neurotrophic factor (BDNF) and peripheral blood mononuclear cell (PBMC) mitochondria cytochrome c oxidase Vmax activity. Menopausal women showed an increased malondialdehyde (MDA) (p<0.05 vs control) which was normalized by both treatments (p<0.05), but MV failed to do so in the BMI ≥26 subgroup (p<0.05). All other redox enzymes and BDNF were significantly lower in menopausal women and they responded only to FPP (p<0.05). Carbonyl protein level was higher in "BMI ≥ 26" subgroup (p<0.05) and reduced only by FPP (p<0.05). The PBMC cyclooxygenase to citrate synthase activity was reduced (<40%) in the menopausal group (p<0.01) and only FPP caused a significant restoration (p<0.05). Although preliminary, these data confirm the redox and mitochondrial dysfunction occurring in post-menopause and responsive to FPP but very poorly to high dosage antioxidants. This may lead to potential preventive opportunities in menopause-associated neurodegenerative disease.

Varicose vein stripping vs haemodynamic correction (CHIVA): a long term randomised trial.

OBJECTIVES: To compare the long-term results of stripping vs. haemodynamic correction (Ambulatory Conservative Haemodynamic Management of Varicose Veins, CHIVA) in the treatment of superficial venous incompetence resulting in chronic venous disease (CVD). DESIGN: Randomised comparative trial. PATIENTS: 150 patients affected by CVD, CEAP clinical class 2-6, were randomised to saphenous stripping or to CHIVA. METHODS: The clinical outcome was assessed by an independent observer who recorded the Hobbs clinical score for treated limbs. A subjective report of the outcome was provided by the patients. Recurrence of varices was assessed by both clinical examination and duplex ultrasonography. RESULTS: The mean follow-up was 10 years, 26 patients were lost to follow-up. The Hobbs score similar in the stripping and CHIVA groups. However recurrence of varicose veins was significantly higher in the stripping group (CHIVA 18%; stripping 35%, P<0.04 Fisher's exact test), without significant differences in the rate of recurrences from the sapheno-femoral junction. The associated risk of recurrence at ten years was doubled in the stripping group (OR 2.2, 95% CI 1-5, P=0.04). CONCLUSIONS: Recurrent varices occurred more frequently following saphenous stripping than after CHIVA treatment. The deliberate preservation of the saphenous trunk as a route of venous drainage in the CHIVA group may have been a factor reducing the recurrence rate.

Alternative saphenous vein sparing surgery for future grafting.

OBJECTIVE: Evaluation of long saphenous vein sparing surgical procedures alternative to high ligation and distal stab avulsion, in terms of effectiveness and suitability for eventual by-pass surgery. EXPERIMENTAL DESIGN: Prospective evaluation of 125 operations for primary varicose veins, 52 external valve-plasties of the sapheno-femoral junction (EV-SFJ) (42 performed using the hand sewing technique and 10 using the Veno-cuff device), mean follow-up 45 months, and 73 hemodynamic correction of varicose veins (French acronyms: CHIVA), mean follow-up 30 months. SETTING: Department of General Surgery, University of Ferrara. Institutional practice, one-day surgery. PATIENTS: Patients were selected using clinical, Doppler cw, and duplex scanning evaluations. Patients with early varices due to sapheno-femoral reflux with duplex scanning evidence of mobile valve leaflets underwent EV-SFJ. The other patients were operated on using the hemodynamic correction technique. Both groups underwent preoperative ambulatory venous pressure (AVP) and light reflection rheography-refilling time (LRR-RT) measurements. INTERVENTIONS: EV-SFJ restores valve function correcting vein wall dilitation by applying an external prosthesis. CHIVA consists of selected ligatures of the superficial veins that allow superficial blood aspiration in the deep veins through the perforators. MEASURES: The outcome was evaluated with clinical and ultrasonographic examinations, AVP and LRR-RT measurements. RESULTS: Long saphenous vein patency registered after EV-SFJ and CHIVA was 94.2% and 90.4%, respectively. Both treatments preserve the drainage function in the saphenous system. Varicose veins recurrence percentage rate was 9.6% and 10.9%, respectively. CONCLUSIONS: Following the proposed selection criteria, these two alternative procedures seem to be more effective in varices treatment than high ligation and have the advantage of preserving saphenous veins suitable for eventual by-pass surgery.

Intraoperative cholangiography in laparoscopic cholecystectomy during residency in general surgery.

BACKGROUND: The role of laparoscopic intraoperative cholangiography (IC) in the diagnosis of asymptomatic choledocholithiasis is still controversial. The aim of this study was to evaluate the diagnostic-therapeutic impact and the educational implications of this method for residents specializing in general surgery. METHODS: We reviewed the records of 835 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis without choledocholithiasis. IC was routinely performed by both expert surgeons and residents in general surgery. RESULTS: The cholecystectomy was completed laparoscopically in 804 cases, but conversion to open surgery was required in 31 cases. IC was not completed in 140 cases (17.4%), and in 44 cases it revealed a suspected choledocholithiasis. The stones were treated via laparoscopy in 36 cases, laparotomy in six cases, and endoscopic retrograde cholangiopancreatography (ERCP) in two cases. Five patients were not diagnosed wit h choledocholithiasis. In one case, a lesion of the choledochus was discovered and treated laparoscopically. A total of 610 IC were done by expert surgeons and 225 by residents. The duration of the cholecystectomy with IC was significantly different between the two groups (76.9 +/- 12 vs 92.4 +/- 11), as was the feasibility index (88.6% vs 80.6%). CONCLUSIONS: Laparoscopic IC is a safe and accurate procedure for the diagnosis of unrecognized choledocholithiasis. Teaching of this procedure as part of the specialization in general surgery would be opportune because it would provide surgical residents with an additional tool for the diagnosis and treatment of this pathology of the common bile duct.

Breast reconstruction with abdominal flaps after abdominoplasties.

After the reported safe transverse rectus abdominis myocutaneous (TRAM) flap after liposuction of the abdomen, two cases of bipedicled reconstruction with this flap after abdominoplasty were successfully performed. This operation has not previously been considered possible because of the transection of the perforator arteries during the undermining of the abdomen. To examine the possible reperfusion of the perforator arteries, the authors studied the perforator arteries of 10 patients before they underwent abdominoplasty and at 1 week, 3 months, and 6 months after the operation. The arteries were studied with color-duplex scanning and power Doppler, using 10-MHz superficial probes, and their position was marked on a map. A cadaver study of a woman who had had an abdominoplasty 10 years before her death is also presented. In every patient, reperfusion of all perforator arteries was documented, starting from the control at 1 month. In no case was the caliber of the reperfused vessels more than 40 percent of the original diameter (maximum: 0.53 mm). This was also confirmed by the cadaver study. In conclusion, after an abdominoplasty operation, constant reperfusion of the perforator arteries of the rectus muscles occurs. However, the diameter of the arteries may not be enough to provide the necessary blood supply for a TRAM flap, which is therefore strongly discouraged by the authors after abdominoplasty in favor of a vertical rectus abdominis muscle (VRAM) flap. A liposuction, which does not necessarily disrupt the perforators, is not an absolute contraindication for a TRAM flap, provided that an accurate color-duplex scanning study is done.

Saphenous vein sparing surgery: principles, techniques and results.

OBJECTIVE: Evaluation of saphenous vein sparing surgical procedures alternative to high ligation and distal stab avulsion, in terms of effectiveness and suitability for eventual bypass surgery. EXPERIMENTAL DESIGN: Prospective evaluation of 421 operations for primary varicose veins, 64 external valve-plasties of the sapheno-femoral junction (EV-SFJ), (42 performed using the hand sewing technique and 22 using the Veno-cuff device), mean follow-up 52 months, and 357 hemodynamic correction of varicose veins (French acronymis CHIVA), mean follow-up 49 months. Moreover, a subgroup of 27 patients was operated on using the CHIVA technique in two steps, mean follow-up 18 months. SETTING: Institute of General Surgery, University of Ferrara. Institutional practice, one-day surgery. PATIENTS: Patients were selected using clinical and duplex scanning evaluations, and classified according to CEAP criteria. Patients with varicose veins due to sapheno-femoral reflux with duplex scanning evidence of mobile valve leaflets underwent EV-SFJ. The other patients were operated on using the hemodynamic correction technique. INTERVENTIONS: EV-SFJ restores valve function correcting vein wall dilatation by applying an external prosthesis. CHIVA consists of selected ligatures of the superficial veins that allow superficial blood aspiration in the deep veins through the perforators as well as the preservation of saphenous drainage. MEASURES: The outcome was evaluated with independent clinical and ultrasonographic examinations; pre and postoperative AVP and LRR-RT measurements were assessed in 125 cases. Data from self-assessment of the functional and cosmetic result of the patients of the CHIVA group were also obtained using a scoring system. Moreover, scanning the preserved long saphenous vein the rate of long saphenous vein suitable as arterial conduit following sparing surgery was also evaluated. RESULTS: Overall long saphenous vein patency registered after EV-SFJ and CHIVA was 94%. Varicose veins recurrence rate was 12% and 11%, respectively. Postoperative AVP and LRR-RT improvement was statistically significant (p<0.001). CONCLUSIONS: These two alternative procedures seem to be effective in varices treatment following the proposed indications and techniques. In addition, they appear able to preserve a more significant rate of saphenous veins suitable for eventual bypass surgery than high ligation and multiple cosmetic avulsion.

Angiovideo-assisted hemodynamic correction of varicose veins.

OBJECTIVE: Evaluation of the feasibility and utility of angioscopy in the hemodynamic correction (French acronyms is CHIVA) of primary varicose veins disease. EXPERIMENTAL DESIGN: Prospective evaluation of 25 patients, undergoing hemodynamic correction of primary varicose disease with intraoperative videoangioscopic guide. Patients have been selected according to criteria emerged from a prospective study that we had previously conducted. Follow-up lasted 1 year (range 8-18 months). SETTING: Department of Surgery, University of Ferrara, Italy. Institutional practice. One-day surgery. PATIENTS: Their selection has been carried out in our Vascular Laboratory. The adopted clinical criteria of selection were: Primary varicose disease of the long saphenous vein territory, no previous thrombophlebitis and/or sclerotherapy. Doppler cw and Duplex criteria followed were: competent deep venous system, long saphenous vein diameter minor than 10 mm and incompetent perforating veins diameter minor than 4 mm. INTERVENTIONS: 25 hemodynamic corrections according to the CHIVA method described by Franceschi. An angioscope, introduced through a distal collateral of the long saphenous vein, permitted the precise interruption of the venous-venous shunts and of the superficial venous system, just below the perforators chosen as re-entry points in the deep venous system. MEASURES: Clinical: varices and symptomatology reduction. Duplex and Doppler cw: detection of the superficial blood flow re-entry, in the deep venous system, through the perforators and identification of recurrences or new refluxes. Pre and postoperative Ambulatory Venous Pressure and Refilling Time have also been measured. RESULTS: In 20 patients symptoms and varices relief were recorded (80%), in 5 patients varices reduction was observed only during walking (20%). In 2 of these latter patients there was no re-entry through the perforators, with a recurrent sapheno-femoral reflux in 1 of them. Early complications recorded were: 2 long saphenous vein thrombosis (8%); 7 ecchimosis (28%) when heparine/saline solution had been used for angioscopic clearance. CONCLUSIONS: Intraoperative angioscopy is feasible and useful when the hemodynamic situation is complex and the Duplex map is difficult to be interpreted by the surgeon. In this series the second look percentage rate has been minor compared to the percentage rates published so far by other authors.

The relationship between in vitro and in vivo venous compliance measurement.

OBJECTIVE: To assess the relationship between in vitro and in vivo venous compliance measurement. DESIGN: Prospective, blind study. MATERIALS AND METHODS: Patients affected by primary varicose veins and classified in accord with the new CEAP criteria (C2-6/S, Ep, AS1-4/p17-18, PR) underwent blind venous compliance measurements using two different methods. 1) In vivo assessment of the compliance of the greater saphenous vein by duplex scanning, for diameter, and a needle transducer, for venous pressure measurements. 2) In vitro standard compliance assessment of the same vein segment after its excision. RESULTS: The compliance values obtained with the two methods showed a significant degree of correlation, which improved with increasing intravenous pressures. CONCLUSIONS: In vivo compliance assessment of the saphenous vein was validated by the relationship with the standard in vitro measurement.

[Clinical and hemodynamic effects of external valvuloplasty of the sapheno-femoral junction]. / Effetti clinici ed emodinamici della plastica esterna delle valvole del giunto safeno-femorale.

Selected patients with primary varicose vein disease and sapheno-femoral reflux as the only point of regurgitation in the affected lower limb and duplex evidence of mobile valve leaflets underwent external valvuloplasty of the sapheno-femoral junction. Operations were performed under local anesthesia in one day-surgery. One PTFE sleeve 0.4 mm thick, in average 1.2 cm long and able to uncircle a circumference in average of 1.7 cm was put around the terminal Long Saphenous vein valve, located in the last centimeter of this vein. If also the subterminal Long Saphenous Vein valve site, located 5 cm below is dilated a second valvuloplasty was performed. In 15 case we used intra-operatory video-angioscopy guide. This examination allowed us to exclude two patients with valve damages not duplex demonstrable. Furthermore angioscopy permitted immediate demonstration of restored valvular function. Follow-up lasted on average 48 months: two early postoperative long saphenous vein thrombosis, and two late sapheno-femoral reflux recurrences were the main complications. We never observed graft infection. AVP was reduced and RT, measured by the means of LRR, had a prolongation after surgery. Both measurements had an highly significant difference from a statistical point of view, comparing pre and postoperative values. 95% of the operated patients have stable varices reduction. Long Saphenous Vein patency was recorded in 37 cases (92.5%). On the contrary, after high ligation, the fate of the saphenous vein in 21% of case is the occlusion. Symptoms of venous insufficiency disappeared completely in 80% of cases and improved in 95% of the operated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Our experience with lymphocytes activated against cancer: CTL cells]. / La nostra esperienza con linfociti attivati contro il cancro: le cellule CTL.

Our group, thanks to the considerable help offered by prof. S. Fujimoto, Chief of the Immunologic Oncology Department of the Kochi Medical School (Japan), developed a method of "in vitro" activation of cytotoxic T lymphocytes (CTL), which are directed against tumour-specific antigens MHC-linked of the tumor cells. A protocol of specific immunotherapy based on the use of the CTL cells appropriately manipulated as therapeutic agents is our goal. The protocol recognizes five essential points: 1) retrieve and culture of tumor cells; 2) retrieve of T Lymphocytes; 3) induction of CTL cells; 4) assay of CTL activity; 5) reinfusion of the activated CTL cells to the patient.

A double-blind, rct testing beneficial modulation of BDNF in middle-aged, life style-stressed subjects: a clue to brain protection?

INTRODUCTION: The aim of this prospective study was to see whether LD-1227, a quality-controlled marine nutraceuticals shown to protect experimental stress-induced hyppocampal degeneration, could beneficially modulate BDNF, as measured in the serum, in otherwise healthy but work-stressed individuals. MATERIALS AND METHODS: Forty-eight men and women between the ages of 38 and 62 reporting high-demanding work activity but with an overall positive attitude towards their personal life were recruited. Subjects were divided in two group (24 patients each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo. A third group of healthy non-stressed subjects was used as well. Blood samples were taken before and after the supplementation period. Unstimulated saliva was collected and tested for amylase while serum levels were used to measure BDNF. State Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI) and psychological well-being assessment (PSWB) were measured too. Patients with Val66Met functional polymorphism of BDNF excluded those given their reported association with an impaired release of BDNF. RESULTS: RESULTS showed that, as compared to healthy, non-stressed individuals, stressed ones has a trend decrease of BDNF and this was significantly increased by LD 12-1227 supplementation and the same inverse phenomenon occurred to salivary amylase (p<0.05). No change was noted in the PSQI score but, either STAI or PSWB tests scored better in LD-1227 supplemented subjects. CONCLUSION: The present data suggest that LD-1227 is beneficially affecting neuromodulation and related symptoms during common stressful life conditions and may have the potential as tools in a neuroprotective clinical strategy.

When CHIVA treatment could be video guided.

BACKGROUND: Hemodynamic correction (CHIVA) is a conservative, ambulatory, and controversial varicose vein treatment. It consists of selected ligatures of the superficial venous system decided by means of preoperative duplex mapping. OBJECTIVE: Prospective evaluation of 80 patients, operated on according to the CHIVA technique described by Claude Franceschi. Mean follow-up length was 30 months. METHODS: Fifty-five consecutive patients were operated on after clinical, ultrasonographic, ambulatory venous pressure and light reflection rheography evaluations. After a 3-year follow-up, another 25 consecutive patients were selected applying some exclusion criteria that emerged in the first part of the study. This second series was operated on by means of intraoperative angioscopy. The same preoperative evaluations have been used to study the outcome in all patients. RESULTS: CHIVA failed in the short saphenous vein territory varices and when the long saphenous vein and the insufficient perforating veins had a preoperative diameter greater than 10 and 4 mm, respectively. The procedure showed a long saphenous vein patency of 90.4% and registered a total recurrence rate of 18.7%. CONCLUSIONS: CHIVA seems to be a more effective varicose vein treatment than high ligation and distal stab avulsion. It also preserves a higher rate of long saphenous veins, suitable for bypass surgery.

Ultrasonographic assessment of ambulatory venous pressure in superficial venous incompetence.

PURPOSE: In spite of its invasiveness, measurement of ambulatory venous pressure (AVP) is widely considered the gold standard measurement of venous function. We studied a technique for noninvasive ultrasonographic AVP determination in superficial venous incompetence. METHODS: A linear relationship between venous pressure (measured by echo-guided venous puncture) and diameter (measured by transverse axis duplex imaging) was preliminarily demonstrated with multiple measurements in different conditions (supine, sitting, standing, and Trendelenburg positions, after exercise with and without cuff occlusion) in a saphenous tract at the thigh of 82 limbs in which reflux had been previously demonstrated. Then AVP was measured in another group of 44 patients who had demonstrated superficial venous incompetence, both with and without proximal occlusion, using again the same invasive method and a new noninvasive technique. The latter technique consisted in the construction of a linear diameter/pressure curve obtained after saphenous diameter (by high-resolution sonography) and noninvasive pressure (using hydrostatic values) determinations in the sitting and standing positions. Further measurement of saphenous diameter after standardized exercise permits extrapolation of the AVP values from the curve. RESULTS: Linear regression analysis demonstrates that (1) beginning from 20 mm Hg, the pressure/diameter relationship of the incompetent greater saphenous vein is linear; and (2) AVP values derived invasively and noninvasively are significantly correlated (r = 0.7347 and p < 0.0001 for AVP derived without occlusion; r = 0.7270 and p < 0.0001 for values recorded with occlusion). CONCLUSIONS: The proposed technique appears able to reliably assess noninvasively AVP values in superficial venous incompetence. In addition, it can be performed with equipment that is widely used for vascular investigations.

Enzymatic determination of faecal bile acids. A simple test for bile acid malabsorption.

A simple method for total faecal bile acid (FBA) determination was carried out. This test involves a 72 hour stool collection, homogenization and FBA determination by means of an enzymatic-fluorimetric method (3 -Hydroxysteroid-dehydrogenase). The reliability of this test was discussed. FBA levels were tested in twelve healthy volunteers. In addition, two patients with bile acid malabsorption syndrome due to terminal ileitis and one patient with cholegenic diarrhoea caused by biliocolonic fistula were examined. The mean +/- SD of FBA values in healthy subjects was 0.49 +/- 0.3 g/72 hours. However, all patients tested show a marked increase of FBA levels. In conclusion the present method for bile acid determination in the faeces seems to be a useful tool in the diagnosis of bile acid malabsorption syndrome and in cholegenic diarrhoea.

In vitro versus in vivo assessment of vein wall properties.

Venous compliance reflects the mechanical properties of the vein wall. Clinical methods of measurement have not been validated by comparison with the accepted in vitro measurement. Despite this, clinical assessment of vein compliance may have a series of useful applications: (1) to assess the progression of chronic venous insufficiency and the related hemodynamic forces acting on the saphenous vein wall; (2) to determine the suitability of the saphenous vein for replacement of an arterial conduit by testing its mechanical properties; and (3) to select the saphenous vein with preferable mechanical performance for coronary artery bypass. The aim of this study is to assess the relationship between in vitro and two in vivo methods of compliance measurement. Compliance of the saphenous vein was determined in 20 patients, using both an invasive and a noninvasive (A and B, respectively) method. Duplex scanning was used for diameter measurement. Venous pressure was derived either intravenously with a needle transducer, or noninvasively with limb length measurement. Patients underwent saphenous excision with further in vitro compliance measurement of the same vein segment (method C). The compliance values obtained with the three methods showed different degrees of correlation (r= 0.516, p = 0.0001 for method A versus method C; r = 0.658, p = 0.0001 for method B versus method C; r = 0.993, p = 0.0001 for method A versus method B). The relationships with the in vitro measurements that were determined validate both in vivo methods for assessment of saphenous vein compliance. Due to its completely noninvasive design, method B appears to have potential use for clinical assessment of saphenous vein wall properties.