Prophylaxis of central venous catheter-related thrombosis with minidose warfarin: analysis of its use in 427 cancer patients

BACKGROUND: In the past few years, several studies have been performed to evaluate thrombosis prophylaxis with warfarin in cancer patients with central venous catheters (CVC), but the analysis of these studies does not allow firm conclusions to be drawn. PATIENTS AND METHODS: Four hundred and twenty-seven cancer patients were evaluated. Each received warfarin at a dose of 1 mg/daily as prophylaxis, starting the day after CVC positioning until its removal. RESULTS: The catheters were monitored for a mean of 168 days (range 22-706). There were 9 thrombotic events (1.8%). Overall, International Normalised Ratio (INR) elevation occurred in 55 (12.8%) patients. Bleeding was observed in 15 (3.5%) patients, 10 of whom had elevated INR levels. Of these, all were treated with continuous-infusion 5-Fluorouracil (5-FU)-based regimens. CONCLUSION: Minidose warfarin can protect from clinical thrombosis, but can induce an alteration in INR values and/or haemorrhagic symptoms in patients being treated with 5-FU-based regimens.     

Sudden cardiac death due to hypersensitivity myocarditis during clozapine treatment

The case concerns the sudden death of a 29-year-old male during clozapine therapy started 2 weeks before. He had a history of treatment-resistant chronic schizophrenia. A complete immunohistochemical study was performed on heart specimens. Histologically, the heart presented diffuse eosinophilic infiltrates located around perivascular structures and focal myocyte necrosis with numerous interstitial eosinophils admixed with histiocytes. The diagnosis of acute myocarditis with an eosinophilic infiltrate was established as the cause of death. The autopsy findings and a detailed medical history supported the conclusion that clozapine-induced hypersensitivity myocarditis was the most likely cause of death.     

The role of interleukin-6 and of its soluble receptors in the biocompatibility of dialysis treatment

Proinflammatory cytokines, in addition to their role in host defence, may be considered mediators of disease; a reduction of cytokine synthesis or effects is, therefore, becoming a target of many diseases. IL-6 is a pro-inflammatory cytokine that may play a role in several clinical problems related to dialysis treatment. An enhanced spontaneous production of IL-6 by Peripheral Blood Mononuclear Cells (PBMC) harvested from ESRD patients dialyzed with a poor biocompatible membrane has been first demonstrated by our group. These results were also obtained in patients undergoing continuous peritoneal dialysis, in absence of peritonitis. We have also demonstrated that IL-6 release was inversely correlated with serum albumin changes. Biological activities of IL-6 may be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R may enhance the inflammatory effects of IL-6 and is, therefore, an "agonistically" acting molecule. We have recently studied sIL-6R production in ESRD patients dialyzed with different membranes; the conclusion was that poor biocompatible membranes, via the sIL-6R, might further increase the inflammatory effects of IL-6. On the contrary, sgp130 can efficiently bind the IL-6/sIL-6R complex with "antagonistic" effects. We have evaluated plasma levels of sgp130 in 18 ESRD patients regularly dialyzed with hemophan membranes (HE) and in 15 patients dialyzed with more biocompatible synthetic membranes (BIO). Our results demonstrate that plasma levels of sgp130 in HE are 33% higher than in both healthy controls and BIO. Circulating levels of sgp130 were correlated positively with C-reactive protein (r: 0.338, p<0.05) and negatively with serum albumin (r: -0.334, p<0.05). These results suggest that higher circulating levels of sgp130 are likely associated with higher IL-6 levels. These higher amounts are probably insufficient to control the activity of IL-6 and may be considered only as a marker of PBMC activation.     

Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study

PURPOSE: We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy. MATERIALS AND METHODS: A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment. RESULTS: In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup. CONCLUSIONS: In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.     

Assessment of bladder and urethral sphincter function before and after radical retropubic prostatectomy

PURPOSE: In a prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on detrusor and urethral sphincter function by comparing urodynamic status preoperatively with that during longitudinal followup. MATERIALS AND METHODS: A total of 49 consecutive patients underwent urodynamics with pressure flow studies and Valsalva leak point pressure measurements 3 to 7 days before RRP (baseline), and then 1 and 8 months after surgery. We assessed bladder compliance, detrusor overactivity, detrusor contractility and intrinsic sphincter deficiency (ISD). RESULTS: There was no significant change in detrusor overactivity at 1 and 8 months of followup. Decreased bladder compliance was observed in 20.4% of patients at baseline, and in 38.7% and 30.6% at 1 and 8 months, respectively. De novo decreased compliance was detected in 18.4% and 10.2% of patients at the same points. Impaired bladder compliance was comparable to that before surgery in 20% of cases. Impaired detrusor contractility was detected in 42.8% of patients at baseline, and in 61.2% (p <0.05) and 42.8% at 1 and 8 months, respectively. De novo hypocontractility was observed in 28.6% and 10.2% of patients at 1 and 8 months, respectively. A strong association between detrusor overactivity and ISD was observed at 1 and 8 months (p <0.01). CONCLUSIONS: Following RRP detrusor hypocontractility and decreased bladder compliance represent de novo transient dysfunction probably due to bladder denervation and an established condition not influenced by the operation. The strong association between overactivity and ISD suggests that stress urinary incontinence increases urethral afferent nerve activity and induces involuntary detrusor contractions.     

Band Erosion after Laparoscopic Gastric Banding: Occurrence and Results after Conversion to Roux-en-Y Gastric Bypass

Background: Laparoscopic adjustable gastric banding is a popular bariatric operation. Unfortunately, long-term complications such as slippage, infection, and intragastric migration (erosion) may occur. With erosion, band removal is mandatory. Options to prevent weight regain are delayed implantation of a new band, or conversion to another bariatric procedure such as Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion. We present our experience with band erosion and immediate or delayed conversion to RYGBP. Methods: With a multidisciplinary team approach and prospective data collection, a comparison was made between patients with and without band erosion. The patients who were converted to RYGBP for band erosion were analyzed. Results: Gastric banding was performed on 347 patients between 1995 and 2002. Median follow-up is 52 months. Band erosion developed in 24 patients (6.8 %).The latter were heavier before gastric banding (BMI 45.9 vs 43.3, P <0,01). No band had ever been overinflated. Band erosion was diagnosed after a mean of 22.5 months (3-51). At time of diagnosis, mean BMI of 33.5 kg/m² (22.5-48) and average excess weight loss (EWL) of 52.9% (25-97) did not differ from that of the remaining patients at the respective time interval. The band was removed in all cases. Conversion to RYGBP was performed at the same time in 11, and a few months later in 2 patients. Operative morbidity included 1 leak (reoperation) and 4 wound infections. All but 1 patient lost further weight after reoperation, or at least maintained their weight. At last follow-up, mean EWL in relation to the pre-banding weight was 65.1%, and 69.2% of the patients had an EWL >50%, which compares favorably with the results obtained after primary RYGBP. Conclusions: In our series with a median follow-up >4 years, band erosion was more common than usually reported. Band removal with immediate or delayed conversion to RYGBP is feasible with an acceptable morbidity, and prevents weight regain in most cases. These results support further use of this approach for band erosion.     

Circulating CD34+, CD133+, and vascular endothelial growth factor receptor 2-positive endothelial progenitor cells in myelofibrosis with myeloid metaplasia.

PURPOSE: Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. We measured the number of circulating EPCs in patients with myelofibrosis with myeloid metaplasia (MMM), and we examined the relationship between the number of EPCs and severity of the MMM disease process. PATIENTS AND METHODS: The number of EPCs was measured by assaying the CD34+CD133+ vascular endothelial growth factor receptor 2 (VEGFR2) -positive cell phenotype in 110 MMM patients, 16 patients with other Philadelphia-negative chronic myeloproliferative disorders (Ph-negative CMPDs), and 14 healthy participants. In four MMM patients, the capacity of selected CD34+ cells to form endothelial colonies (CFU-End) in vitro was tested. RESULTS: CD34+, CD133+, and VEGFR2-positive EPCs were detectable in unselected peripheral-blood cells of 50.9% MMM patients, 37.5% control patients, and 21% healthy participants. Patients with MMM had a median of 0.26% EPCs, significantly higher than that in healthy controls (median, 0%) and in patients with other Ph-negative CMPDs (median, 0.1%). In 14.5% of MMM patients, the numbers of EPCs were greater than the highest value found in patients with other Ph-negative CMPDs. CD34+ selected cells produced colony-forming unit-endothelial (CFU-End), which were vascular endothelial (VE) -cadherin positive, CD31+, von Willebrand factor positive, and CD45-. In MMM patients, the larger the number of EPCs, the smaller the number of circulating immature myeloid cells and circulating CD45+CD34+ hematopoietic progenitor cells. Increased numbers of EPCs were associated with younger age and a diagnosis of prefibrotic MMM. CONCLUSION: Circulating EPCs are elevated in MMM patients in the early stage of the disease. Heightened mobilization of EPCs may represent an important mechanism for development of neoangiogenesis in MMM.     

Human herpesvirus 7 infection impairs the survival/differentiation of megakaryocytic cells

In vitro infection of CD61+ megakaryocytic cells with human herpesvirus-7 (HHV-7) induced a drastic increase of apoptosis. Moreover, cells surviving HHV-7 cytotoxicity showed enhanced megakaryocytic maturation with respect to control cultures. These data suggest that HHV-7 reactivation in the bone marrow of HIV-1 infected individuals may contribute to impair megakaryocytopoiesis.