Use of human fibrinogen and human thrombin for urethral reconstructive surgery

The objective of the present study is to test the use of a haemostatic sponge for urethral reconstructive surgery and to assess the relevant benefits. METHODS. The haemostatic sponge is made up of collagen with human fibrinogen and human thrombin. When the sponge gets in contact with fluids, such as blood, lymph or saline solution, the fibrinogen and thrombin are activated and form a fibrin net able to achieve local haemostasis and tissue regeneration. This kind of product was used in 30 selected patients (pts.), aged 19 - 70 (mean age: 35), who underwent single-stage anastomotic urethroplasty from January 2006 to March 2007: 22 bulbar end-to-end anastomoses and 8 bulbo- prostatic anastomoses. All operations were performed due to post-traumatic stricture of bulbar and posterior urethra. The main selection criterion for the use of the haemostatic sponge has always been the tendency to and/or the presence of bleeding in the different surgical stages. The sponge imbibed in saline solution and suitably modeled for all specific requirements was differently placed: sleeve-shaped in the case of bulbar anastomoses (16 pts.); as a "patch" in the centre of spongioplasty in bulbo-prostatic anastomoses (8 pts.), and within the widening incisions of the urethral roof performed between the two cavernous bodies at level of the intercrural septum (5 pts.). In 1 case (obese patient) a single sponge was placed after the deep perineal reconstruction on the bulbo-cavernous muscle- subcutaneous layers because of massive bleeding. RESULTS. In all cases a perfect control of haemostasis could be achieved, with immediate end of bleeding in the points where the haemostatic sponges were used. The dressings performed on day 3 upon removal of the compressive scrotum-perineal bandages did not show any late post-operative bleeding. The follow-up visits at month 1 and 3 yielded positive outcomes for all 30 patients, who achieved complete wound healing by first intention, and a perfect anastomosis especially in the bulbar end-to-end urethroplasty, confirmed by urethrografy at one month. CONCLUSIONS. The association of human fibrinogen and human thrombin in haemostatic sponges represents a manageable, useful product, apparently sure, not negatively interfering in repairing and regenerating tissue processes, and allowing a simple and direct control of important bleeding events occurring during urethral reconstructive surgery as well as other operations. It is therefore advisable to more widely use the product after a suitable followup period.     

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor

Background and aimsContinuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS).Methods and resultsSubjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS? glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day.Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38–20.65]% for the DG5 and 10.75% [5.15–19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14–14.30]% vs 11.4% [5.04–18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was ?0.5 to ?1.5 mg/dL/min, with median ARD of 7.34% [3.71–12.76]% vs 13.59% [4.53–20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09–15.29]% vs 12.73% [4.14–20.82]% (p-value = 0.02).ConclusionsDG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.     

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss

Background and aimsWe investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome.Methods and resultsEighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic + resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA_1c decreased in Groups B–D. VO_2max, HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO_2max and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D.ConclusionPhysical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.     

Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study.

Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.     

The retinoblastoma family member pRb2/p130 is an independent predictor of survival in human soft tissue sarcomas

PURPOSE: pRb2/p130, a member of the Retinoblastoma gene family, has been shown to be a powerful prognostic factor in several malignancies. We sought to evaluate pRb2/p130 protein expression and its clinical effect in patients affected with soft tissue sarcomas (STS). EXPERIMENTAL DESIGN: Expression of pRb2/p130 was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded sections in 41 STSs. Results obtained were correlated with clinicopathologic variables and disease-free and overall survival (OS) in univariate and multivariate analysis. RESULTS: Expression of pRb2/p130 was diminished in 25 (61%) tumors, whereas the remaining ones (39%) were classified as high expressors. No correlation between pRb2/p130 expression and clinicopathologic variables was observed. However, a direct relationship between pRb2/p130 expression and clinical outcome of the patients was found in the subgroup of nonmetastatic tumors (n = 31). In univariate analysis, reduced pRb2/p130 expression was a negative prognostic factor and correlated with shorter disease-free survival (P = 0.021) and OS (P = 0.017) survival. In multivariate analysis, reduced pRb2/p130 expression was confirmed to be an independent predictor of shorter OS when considered together with tumor stage and grading (risk ratio, 7.893; confidence interval, 1.618-38.509; P = 0.011). CONCLUSIONS: This study shows for the first time the potential prognostic value of pRb2/130 expression evaluated on formalin-fixed, paraffin-embedded sections in STSs patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with nonmetastatic STSs and, therefore, may represent a new prognostic marker.     

Selective lesions of rabbit extraocular muscles injected with the anti-AChR immunotoxin saporin-mAb 73

PURPOSE: To evaluate the effects on extraocular muscles of a skeletal muscle-specific immunotoxin, saporin-mAb 73, as an alternative to botulinum toxin to induce a permanent correction of oculo-facial dystonias or some forms of ocular motility disorders. METHODS: An immunotoxin was prepared with a monoclonal antibody (mAb 73) against acetylcholine receptors of skeletal muscle, linked to saporin, a type 1 ribosome-inactivating protein (RIP) from Saponaria officinalis. Sixteen New Zealand white rabbits were treated with a single injection of immunotoxin directly into the medial rectus muscle of one eye. Four different dosages of 2, 5, 20, or 50 ng saporin-mAb 73 were used. The rabbits were sacrificed at two, 7 and 14 days post-injection. The medial rectus muscle and the retractor bulbi muscle of both the injected and the fellow eyes were taken and serial sections were examined by light microscopy in a blinded manner. RESULTS: Saporin-mAb 73, even at the dosage of 2 ng, brought about focal damage in the extraocular muscles of rabbits without histological changes in adjacent muscles. The histological examination revealed necrotic/apoptotic lesions restricted to the sites of inoculation and largely infiltrated by macrophages. No evident inflammatory reaction was detected at any time and neutrophils were substantially absent. At 14 days after injection, necrosis/apoptosis was still evident and the sclerotic reaction was minimal. CONCLUSIONS: The immunotoxin saporin-mAb 73 injections into the extraocular muscles of rabbits caused focal damage to the muscles. There was no significant inflammatory reaction and muscle fiber loss was present even at the lower doses. Although the lesions were followed for only 14 days, our results suggest that saporin-mAb 73 has potential to cause safe focal muscle damage but longer-term follow-up are needed to investigate the persistence of muscle weakness.     

A randomised cross-over study on the haemodynamic effects of oral dofetilide compared with oral sotalol in patients with ischaemic heart disease and sustained ventricular tachycardia

OBJECTIVE: To assess the haemodynamic effects of short-term treatment with dofetilide in comparison with sotalol in patients with ischaemic heart disease. METHODS: Twelve patients with ischaemic heart disease and sustained ventricular tachycardia were treated with dofetilide [500 microg twice daily (b.i.d.)] or sotalol (160 mg b.i.d., randomised sequence separated by wash-out period) for 3-5 days. Right-heart catheterisation was performed at baseline and at the end of each short-term treatment phase. RESULTS: The main findings were a significant reduction in heart rate, mean systemic pressure and cardiac index (-13%) during treatment with sotalol. Conversely, cardiac index increased significantly during dofetilide (mean percentage change 11%) with no effect on heart rate and systemic blood pressure. CONCLUSIONS: Oral dofetilide exerts favourable haemodynamic effects in comparison with D,L-sotalol following short-term oral treatment. In view of these observations, the use of dofetilide may be proposed also in patients with ventricular tachyarrhythmias associated with impaired left-ventricular function. Whether the haemodynamic differences between dofetilide and D,L-sotalol are the basis for differences in tolerability remains to be evaluated.