Lung abscess in adults: clinical comparison of immunocompromised to non-immunocompromised patients

Information related to the clinical characteristics and isolated microbes associated with lung abscesses comparing immunocompromised (IC) to non-immunocompromised (non-IC) patients is limited. A retrospective review for 1984-1996 identified 34 consecutive adult cases of lung abscess (representing 0.2% of all cases of pneumonia), including 10 non-IC and 24 IC patients. Comparison of age, gender, tobacco use, pre-existing pulmonary disease or recognized aspiration risk factors were not significantly different between the two groups. Upper lobe involvement accounted for the majority of cases, although multi-lobe involvement was limited to IC patients. There were no differences in the need for surgical intervention, and mortality was very low for both groups. Anaerobes were the most frequent isolates for non-IC patients (30%), whereas aerobes were the most frequent isolate for IC patients (63%). Importantly, certain organisms were exclusively isolated in the IC group and multiple isolates were obtained only from the IC patients.Thus, comparing non-IC to IC patients, clinical characteristics may be similar whereas important differences may exist in the microbiology associated with lung abscess. These findings have important implications for the clinical management of these patient groups, and support a strategy to aggressively identify microbial agents in abscess material.     

Dichloroacetate,a selective mitochondria-targeting drug for oral squamous cell carcinoma: a metabolic perspective of treatment

Reprogramming of metabolism is a well-established property of cancer cells that is receiving growing attention as potential therapeutic target. Oral squamous cell carcinomas (OSCC) are aggressive and drugs-resistant human tumours displaying wide metabolic heterogeneity depending on their malignant genotype and stage of development. Dichloroacetate (DCA) is a specific inhibitor of the PDH-regulator PDK proved to foster mitochondrial oxidation of pyruvate. In this study we tested comparatively the effects of DCA on three different OSCC-derived cell lines, HSC-2, HSC-3, PE15. Characterization of the three cell lines unveiled for HSC-2 and HSC-3 a glycolysis-reliant metabolism whereas PE15 accomplished an efficient mitochondrial oxidative phosphorylation. DCA treatment of the three OSCC cell lines, at pharmacological concentrations, resulted in stimulation of the respiratory activity and caused a remarkably distinctive pro-apoptotic/cytostatic effect on HSC-2 and HSC-3. This was accompanied with a large remodeling of the mitochondrial network, never documented before, leading to organelle fragmentation and with enhanced production of reactive oxygen species. The data here presented indicate that the therapeutic efficacy of DCA may depend on the specific metabolic profile adopted by the cancer cells with those exhibiting a deficient mitochondrial oxidative phosphorylation resulting more sensitive to the drug treatment.     

GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC.     

Disease-Specific Quality of Life in Young Patients With Tourette Syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating “pure” Tourette syndrome from Tourette syndrome “plus” behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.     

Myotonic dystrophy type 1 and de novo FSHD mutation double trouble: A clinical and muscle MRI study

Here we describe the first case of myotonic dystrophy type 1 (DM1) associated with facio–scapulo–humeral dystrophy (FSHD). From a clinical point of view, the patient displayed a pattern of muscle involvement reminiscent of both disorders, including hand-grip myotonia, facial, axial and distal limbs muscle weakness as well as a bilateral winged scapula associated with atrophy of the pectoralis major muscle and lumbar lordosis; pelvic muscles were mostly spared. An extensive muscle MRI assessment including neck, shoulder, abdominal, pelvic and lower limb muscles documented radiological features typical of DM1 and FSDH. Molecular genetic studies confirmed that the proband carried both a pathologically expanded DMPK allele, inherited from his father, and a de novo shortened D4Z4 repeat fragment at 4q35 locus.     

Left-handedness is statistically linked to lifetime experimentation with illicit drugs

Handedness has been linked to an enhanced risk of alcohol abuse, while less is known about other drugs. A convenience sample of 1004 male and female Italian participants (females=58%) from the general community (18 to 65 years old: average age = 30; standard deviation = 10, median = 25) was asked about: handedness (preference in writing); lifetime use of alcohol, tobacco, and illicit drugs; levels of psychological distress, as measured by the General Health Questionnaire (GHQ); and levels of delusion proneness, as measured by the Peters et al. Delusions Inventory (PDI). Overall, 92 individuals (9.2%) were classified as left-handed, with no significant difference reported among genders. Lifetime use of illicit drugs, primarily cannabis, was reported by 20% of the sample. In a multiple logistic regression analysis, after taking into account sex, age, and caseness on GHQ and PDI, left-handed people in the sample were statistically more likely to report lifetime experimentation with heroin, ecstasy/amphetamine, and, marginally, hallucinogens, but not alcohol or tobacco. Different mechanisms might contribute to an explanation of greater lifetime experimentation with some illicit drugs among left-handed people as compared to right-handed people. However, replications with clinical samples are necessary before any definitive statements can be made.