Impact of a specialized outpatient heart failure follow-up program on hospitalization frequency and functional status of patients with advanced heart failure.

BACKGROUND: High rates of morbidity and mortality are observed in patients with advanced heart failure (AHF). AHF is now considered the most costly syndrome in cardiology owing to the substantial economic burden associated with hospitalizations for acute decompensation. A management program that involves specialized follow-up by a multidisciplinary team has been suggested as a desirable strategy for improving outcomes for these patients. ObjectivE: To evaluate the impact of a specialized outpatient heart failure (HF) follow-up program for patients with AHF on frequency and duration of hospitalization for HF and functional status. METHODS: We retrospectively studied 167 consecutive patients with AHF who were referred to the outpatient HF follow-up program in our institution between January and November 2002, of whom 147 followed for > or =30 days were included in the analysis. In addition to demographic and baseline clinical characteristics, HF medication and NYHA functional class, the number and duration of hospitalizations for HF during the previous 12 months were recorded and compared at the time of referral and after a follow-up period of 6.5+/-3 months. RESULTS: Of the 147 patients analyzed (aged 60.8+/-13 years; 79% male; left ventricular ejection fraction 27+/-11%), 67% were in NYHA functional class III, 20% in class II and 13% in class IV at the time of referral. There was a significant improvement in functional class during the mean follow-up period: 55% of the patients were in class III, 37% in class II, 5% in class I and 3% in class IV (p<0.0001). The proportion of patients on beta-blockers or spironolactone increased from 33% and 51% at the time of referral to 69% and 71% respectively after referral (p<0.0001). In the 12 months before referral, 39% of the patients had been hospitalized for acute decompensation of HF (87 hospitalizations - mean 7.2/month) versus 13% of the patients during the mean follow-up period (25 hospitalizations - 3.8/month, p<0.0001). No significant differences were found in the proportion of patients on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, digoxin or diuretics, or in the mean duration of hospitalization before and after referral. ConclusioN: The specialized follow-up of patients with AHF by a team with expertise in HF resulted in significant therapeutic optimization. Increased use of beta-blockers and spironolactone was associated with significant improvement in functional capacity and significant reduction in hospitalizations.     

Hybrid tumours of the salivary glands. A report of two cases involving the palate and a review of the literature

Hybrid tumours are very rare salivary gland lesions composed of two or more different tumoural entities in a single neoplasm that arise within a definite topographical region. In most cases adenoid cystic carcinoma has been the predominant component in these lesions. In this study we describe two patients with hybrid tumours located in the palate, one in a 49-year-old woman and one in a 71-year-old man. The first case involved adenoid cystic carcinoma and mucoepidermoid carcinoma, and the patient in the second case exhibited adenoid cystic carcinoma and epithelial-myoepithelial carcinoma. Both patients were treated with surgery and radiotherapy, and there has been no evidence of recurrence after 13 and 36 months of follow-up, respectively. The recognition of the histologic component with the higher grade of malignancy in every case of hybrid tumour of the salivary glands is a necessary step to determine the biological behaviour and, consequently, to determine the proper therapeutic approach.     

Comparing reconstruction with ileocecal graft to jejunal interposition pouch after total gastrectomy in rats.

After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation.     

Catalase enzyme mutations and their association with diseases.

Enzyme catalase seems to be the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide at high concentrations is a toxic agent, while at low concentrations it appears to modulate some physiological processes such as signaling in cell proliferation, apoptosis, carbohydrate metabolism, and platelet activation. Benign catalase gene mutations of 5' noncoding region (15) and intron 1 (4) have no effect on catalase activity and are not associated with disease.Catalase gene mutations have been detected in association with diabetes mellitus, hypertension, and vitiligo. Decreases in catalase activity in patients with tumors is more likely to be due to decreased enzyme synthesis rather than to catalase mutations.Acatalasemia, the inherited deficiency of catalase has been detected in 11 countries. Its clinical features might be oral gangrene, altered lipid, carbohydrate, homocysteine metabolism and the increased risk of diabetes mellitus. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. However, there are only limited reports on the syndrome causing these mutations.These data show that acatalasemia may be a syndrome with clinical, biochemical, genetic characteristics rather than just a simple enzyme deficiency.     

Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide.

The goal of this study was to evaluate the potential of albumin nanoparticles as a delivery system for antisense oligonucleotides. Nanoparticles were prepared by a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO) and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO-NPB and PS-NPB). When PO-loaded nanoparticles were incubated with phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization capability for at least 60 min. The antiviral activity was evaluated in MRC-5 fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO nanoparticle formulations significantly increased the antiviral activity of free PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the other hand, PS exhibited significant higher activity than free PO (P<0.001), however, no significant differences were found between PS-nanoparticle and PO-nanoparticle formulations. These findings were well correlated with the intracellular distribution observed for fluorescent oligonucleotide-loaded albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and major nuclear accumulation. In summary, albumin nanoparticles partially protected a PO against enzymatic degradation and improved their presence in the nucleus and thus, increased its efficiency.     

The patella and tibial condyle position after combined and after closing wedge high tibial osteotomy

High tibial osteotomy changes the patella and tibial condyle position, which makes the subsequent total knee replacement technically demanding. From 1 January 1993 to 31 December 2000, combined osteotomy [After the first osteotomy made 2 cm distally to the joint line, a bone wedge is removed based laterally. Its tip ends at the center of the tibial condyle (half bone wedge). The distal part of the tibia is placed into the valgus position and the half bone wedge is placed into the gap opened medially.] was performed on 103 knees and closing wedge osteotomy was performed on 47 consecutive knees. Eighty combined (group A) and 41 closing wedge (group B) osteotomy were studied. All knees were assessed radiologically before surgery, in the 10th postoperative week, in the 12th postoperative month and at the time of the final follow-up (in group A—66.15 months, in group B—66.61 months). We examined the change of the femorotibial angle, of the patellar height according to the method of Insall and Salvati, of the tibial slope angle according to the method of Bonnin, of the tibial condylar offset according to the method of Yoshida and of the distance between the lateral tibial plateau and the top of the fibular head. In group A and B, the recurrence of the varus deformity was not noted and valgus alignment did not increase in any case. In group-A, the Insall–Salvati ratio remained unchanged in 65% of knees. The tibial slope angle decreased in both groups. There was correlation between the change of the tibial condylar offset and the angle of the correction in both groups. There was correlation between the change of the distance between the lateral tibial plateau and the top of the fibular head. After combined osteotomy, the transposition of the tibial condyle and the decrease of the distance between the lateral tibial plateau and the top of the fibular head was less than after closing wedge osteotomy, although the average angle of correction was more after combined osteotomy (11.835°), than after closing wedge osteotomy (9.465°). Theoretically, the recurrence of the varus deformity, the increase of the valgus alignment and (in majority of cases) the shortening of the patellar tendon do not compromise the likelihood of successful conversion to the subsequent total knee replacement, either after combined or after closing wedge osteotomy. The combined osteotomy does not lead to considerable transposition of the tibial condyle and to considerable lateral tibial bone loss; therefore, theoretically, the combined osteotomy does not impair the subsequent total knee replacement.     

In vitro physiological evidence of enhanced antioxidant and neuroprotective action of 2,3-dihydromelatonin, a melatonin analogue.

As the capacity of the endogenous antioxidative system is limited, pharmacological treatment with antioxidants may help to protect neuronal tissue against increased amount of reactive oxygen species produced during oxidative stress. We attempted to improve resistance of rat hippocampal slices exposed to ischaemia in vitro (hypoxia (HYP) accompanied with decreased glucose concentration followed by reoxygenation (ROX)) and thus to diminish the impairment of synaptic transmission after HYP/ROX. We compared the protective features of the melatonin analogue 2,3-dihydromelatonin (2,3-DHM) with melatonin itself. In preliminary experiments, the compound 2,3-DHM compared to melatonin revealed enhanced antilipoperoxidation action in rat brain homogenates exposed to Fe/ascorbate system (-logIC(50) = 4.76 +/- 0.01 versus -logIC(50) = 2.51 +/- 0.02, respectively). In this study, 2,3-DHM (from 0.3 to 10 micromol l(-1)) applied at 30 min before the beginning of HYP and remaining all over the 6-min HYP as well as 20-min ROX, exerted a protective effect demonstrated by improvement of the population spike amplitude (PoS) recovery during ROX, with the maximum effect at 3 micromol l(-1). In accordance with this, the ratio of irreversibly damaged slices after HYP/ROX was decreased in the groups treated with 2,3-DHM. Moreover, a significant delay of PoS decay during HYP (expressed as half time, t(0.5)) was revealed at 2,3-DHM concentration 1 and 3 micromol l(-1)). An equipotent effect of melatonin and 2,3-DHM was achieved by a 100-times lower concentration of the latter (0.3 and 1 micromol l(-1)) compared to that of melatonin (30 and 100 micromol l(-1)). Further, compared to the highest effect of 2,3-DHM in the concentration 3 micromol l(-1) on the percentage of irreversibly damaged slices (only 20%), melatonin did not exert such pronounced effect, either in the concentration 30 or 100 micromol l(-1) (67 and 50%, respectively). We conclude that hydrogenation of the melatonin molecule significantly improved its antihypoxic effect in our model of rat hippocampal slices exposed to ischaemic conditions in vitro, similarly as it enhanced the antilipoperoxidation action of 2,3-DHM in our previous studies. These findings suggest that 2,3-DHM deserves more attention concerning its neuroprotective effect in oxidative stress-associated tissue damage.