Nonfermentative gram-negative bacilli in cancer patients: increasing frequency of infection and antimicrobial susceptibility of clinical isolates to fluoroquinolones

Despite a decline in the frequency of gram-negative infections in cancer patients, there has been an increase in the proportion of such infections caused by nonfermentative gram-negative bacilli (NFGNB). We tested the in vitro activity of several quinolones against NFGNB isolated from cancer patients between February 2000 and February 2003, using a broth microdilution method. Ciprofloxacin was the most potent agent tested against Pseudomonas aeruginosa, although only 80% of isolates were susceptible to it. The newer quinolones (gatifloxacin, moxifloxacin, and garenoxacin) had better activity than ofloxacin, levofloxacin, and ciprofloxacin, against many other nonfermenters (Stenotrophomonas maltophilia, P. fluorescens, and P. putida).     

Autonomic antecedents to variant angina exacerbation after beta-blockade withdrawal

We describe a patient with nonsignificant coronary artery disease who experienced variant angina after beta -blockade withdrawal. Standard therapy with nifedipine and nitrates aimed at suppressing symptoms and typical transient ST-segment elevations was superseded by the reinstitution of metoprolol. The autonomic alternations before and after readministration of metoprolol were analyzed by time and spectral indices of heart rate variability (HRV). Metoprolol reduced the HRV and reversed the low-frequency/high-frequency power ratio toward a more physiological autonomic balance. We conclude that the reinstitution of beta -blocker acted protectively by preventing surges of sympathetic activity on an underlying basis of parasympathetic predominance.     

Brain metastases from epithelial ovarian cancer. The Hellenic Cooperative Oncology Group (HeCOG) experience and review of the literature

BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. A retrospective study of all patients diagnosed with brain metastases from EOC over the last 20 years, according to the Hellenic Cooperative Oncology Group (HeCOG) tumor registry, was conducted. PATIENTS AND METHODS: A total of 1450 patients with EOC were treated within various HeCOG protocols from 1983 to 2004. Seventeen (1.17%) of them developed brain metastases. RESULTS: The median age at diagnosis of brain metastases was 58 years (range, 24 to 77). At initial diagnosis, 2 patients had stage II, 12 had stage III and 3 had stage IV disease. Serous papillary adenocarcinoma was the most common histological subtype [12 patients (71%)]. All patients had received initial cisplatin-based chemotherapy. The median time from initial diagnosis to central nervous system (CNS) relapse was 15.9 months (range, 1.4 to 70.8). The CNS was the only site of disease in 13 (76.5%) patients, whereas 4 (23.5%) patients had additional extracranial disease. Two (12%) patients with isolated single brain lesions underwent surgical excision of the metastases, followed by whole brain radiation therapy (WBRT) and chemotherapy. Four (24%) patients were treated with WBRT alone, 6 (35%) patients with WBRT plus chemotherapy and 2 (12%) had only supportive care, while 3 (18%) patients decided not to have any further treatment after the diagnosis of brain metastases. The median survival time from diagnosis of CNS relapse was 5.7 months (range, 0.2 to 22.6) and the median survival time from diagnosis of EOC was 27.4 months (range, 3.0 to 71.4). In patients with CNS recurrence as the only site of disease, the median survival time from diagnosis of CNS relapse was 5.3 months (range, 0.6 to 22.6) and in those with both CNS and extracranial disease, the median survival time was 3.9 months (range, 0.2 to 11.9) (p=0.5597). There was a statistically significant difference in survival for those treated with WBRT plus chemotherapy (10.0 months) versus those treated with WBRT alone (1.5 months) and those who had only supportive care (0.2 months) (p=0.0003). CONCLUSION: The incidence of cerebral metastases in our patients with EOC was 1.17%, which is consistent with the mean value of all series reported in the literature. The prognosis of patients with brain metastases from EOC is poor. Patients who had WBRT and chemotherapy fared better than those who received WBRT alone.     

A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient?

The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDE5 inhibitors have differences in their pharmacological profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDE5 inhibitors, and its use is limited to patients with mild ED. Treatment failures with oral drugs may be due to medication, clinician and patient issues. The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options.Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited efficacy. Vacuum constriction devices may be offered mainly to elderly patients with occasional intercourse attempts, as younger patients show limited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high satisfaction rates in properly selected patients.All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisation.     

Developing treatment options for metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) represents a devastating lysosomal storage disease characterized by intralysosomal accumulation of the sphingolipid sulfatide in various tissues. Three types of the disease are currently distinguished: the late-infantile, which is the most commonly observed, the juvenile and the adult type. Demyelination represents the main histopathological feature of the disorder, leading to neurological impairment with no curative treatment currently available. Nevertheless, the increased scientific interest on the disease has led to the experimental use of innovative therapeutic approaches in animal models, aiming to provide an effective therapeutic regimen for human patients, as well. This paper provides an overview of developing treatment options among patients with MLD. Apart from hematopoietic stem cell transplantation, already in use for decades, other recent data discussed includes umbilical cord blood and stem cell transplantation, enzyme replacement therapy, gene therapy and autologous hematopoietic transplantation of genetically modified stem cells. Gene therapy with oligodedroglial, neural progenitor, embryonic and microencapsulated recombinant cells represents add-on treatment options still on experimental level.     

HIV‑1 molecular epidemiology in the Balkans: a melting pot for high genetic diversity

The Balkans is a gateway between Europe, Asia, and the African continent, a fact with potential important consequences on the epidemiology of HIV?1 infection in the region. The duration of the HIV?1 epidemics in many countries of the Balkans is similar to the one in the Western European countries. However, striking differences exist in several countries of the region in both the epidemic situation and, even more so, in our knowledge about it. In particular, the molecular epidemiology of HIV in the Balkans is largely unknown. In order to gain some preliminary insight into HIV?1 diversity in the region, we reviewed the available molecular epidemiology data about HIV?1 diversity in 10 countries of the region: Albania, Bulgaria, Croatia, Greece, Montenegro, Romania, Slovenia, Serbia, Turkey, and Hungary, a neighboring country to four Balkan countries. The data were obtained either from published studies or in direct communication with the participating members. The existing molecular epidemiology data revealed a broad diversity in subtype distribution among Balkan countries. In several countries, subtype B is predominant (e.g. Serbia, Slovenia, and Hungary), while in others the proportion of non?B subtypes is much larger (Albania subtype A, Romania subtype F). In some areas, HIV?1 subtype distribution is marked by divergence between different risk groups or transmission routes (e.g. Croatia). Recently, HIV?1/AIDS epidemics in Eastern Europe have been among the fastest growing in the world. Many major contributing factors for the breakout and spread of these epidemics are present in many of the Balkan countries, as reflected through the process of social transition, wars, unemployment, extensive drug use, high sexual risk behavior, as well as other factors. Yet, in the Balkan countries the prevalence rate of HIV?1 infection is low, under 0.1 percent. Concomitantly, the molecular epidemiology of HIV?1 in the Balkans has not been thoroughly studied so far. The review and analysis of the available data indicate a broad diversity of circulating HIV?1 subtypes in the region, with the predominance of non?B clades in some countries, underscoring the need for an ongoing surveillance of HIV?1 diversity. The setup of a collaborative network might provide important information for the better management and control of the HIV?1 epidemic in the area.     

“Is obesity linked to aging?”: Adipose tissue and the role of telomeres

Obesity is a condition in which excess or abnormal fat accumulation may present with adverse effects on health and decreased life expectancy. Increased body weight and adipose tissue accumulation amplifies the risk of developing various age-related diseases, such as cardiovascular disease, type 2 diabetes mellitus, musculoskeletal disorders, respiratory diseases and certain types of cancer. This imbalance in body composition and body weight is now recognized as a state of increased oxidative stress and inflammation for the organism. Increasing oxidative stress and inflammation affect telomeres. Telomeres are specialized DNA-protein structures found at the ends of eukaryotic chromosomes and serve as markers of biological aging rate. They also play a critical role in maintaining genomic integrity and are involved in age-related metabolic dysfunction. Erosion of telomeres is hazardous to healthy cells, as it is a known mechanism of premature cellular senescence and loss of longevity. The association of telomeres and oxidative stress is evident in cultured somatic cells in vitro, where oxidative stress enhances the process of erosion with each cycle of replication. Shorter telomeres have been associated with increasing body mass index, increased adiposity, and more recently with increasing waist to hip ratio and visceral excess fat accumulation. Furthermore, many of the metabolic imbalances of obesity (e.g. glycemic, lipidemic, etc.) give rise to organ dysfunction in a way that resembles the accelerated aging process. This article is a non-systematic review of the evidence linking obesity and accelerated aging processes as they are regulated by telomeres.