Percutaneous US-guided RF thermal ablation for malignant renal tumors: preliminary results in 13 patients

Minimally invasive treatment for small renal cell carcinoma (RCC) can be necessary in selected patients and, anyway, is desirable. In situ ablation techniques, including RFA, have been developed. The aim of this study is to evaluate the feasibility, safety and short-term local effectiveness of percutaneous US-guided RFA in a small series, as well as mid-term patient outcome. Thirteen patients with a total of 18 tumors (17 small lesions, 35 mm in size or less, and a larger one, 75 mm in size) underwent 19 RFA sessions. Seven patients had a solitary kidney, and three suffered from VHL disease, too. We treated four lesions in a patient with a bilateral tumor. In another patient, three lesions were ablated. Seventeen tumors were RCC; one was a metastasis from lung cancer. Eight lesions were parenchymal, six exophytic, two parenchymal/exophytic, one parenchymal/central and one central. A monopolar RF system with multitined expandable electrode needles was used. The 35-mm lesion underwent two sessions; the 75-mm lesion was treated with transcatheter arterial embolization before RFA. Tumors with complete loss of contrast enhancement at short-term CT (or MR) were considered successfully treated. Percutaneous US-guided RFA was always feasible without major complications. The success rate after a single treatment in tumors less than 35 mm in size was 88.2% (15/17) and rose to 94.1% (16/17) after the second treatment of the largest lesion. After a mean 14-month follow-up, no successfully treated lesions recurred locally. Only the patient with metastasis from lung cancer died from disease progression in a further location, while all other patients are alive, with renal function still sufficient to avoid dialysis. US guidance allows an easy and safe percutaneous approach for RFA of small non-parahilar RCC. The treatment is locally effective and can be proposed as a minimally invasive therapy for patients with contraindications to surgery or to those expressing an informed consent. Based on the results of this study and of the literature, mid-term results on the clinical usefulness are very encouraging.Presented at ECR 2003.     

Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS)

OBJECTIVE: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS). METHODS: A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51). Assessments included the Clinical Global Impression-Severity (CGI-S), parent and teacher versions of the Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale (SCS), Social Skills Rating System (SSRS), and Early Childhood Inventory (ECI), and Parenting Stress Index (PSI). RESULTS: Medication effects varied by informant and outcome measure. Parent measures and teacher SWAN scores did not differentially improve with MPH. Parent-rated depression (p < 0.02) and dysthymia (p < 0.001) on the ECI worsened with MPH, but scores were not in the clinical range. Significant medication effects were found on clinician CGI-S (p < 0.0001) and teacher social competence ratings (SCS, p < 0.03). CONCLUSIONS: Preschoolers with ADHD treated with MPH for 4 weeks improve in some aspects of functioning. Additional improvements might require longer treatment, higher doses, and/or intensive behavioral treatment in combination with medication.     

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.     

Factors associated with objective (actigraphic) and subjective sleep quality in young adult women

OBJECTIVE: The aim of this study was to describe factors associated with actigraphic and subjective sleep quality in young women. METHODS: Participants were 73 regularly menstruating women, 20-40 years old, who were not taking oral contraceptives, pregnant, or shift workers. Women contributed an average of 7 nights of actigraphy data during the luteal menstrual cycle phase, resulting in a total of 595 nights of data. RESULTS: One night of actigraphy data was unreliable for measuring total sleep time, sleep onset, and time in bed (intraclass correlation < or =.15) but was acceptable for measuring sleep efficiency and total wake time (intraclass correlation [ICC]=.52). Going to bed late, medication use, employment, increased daylight hours, longer menstrual cycle length, and higher body mass index (BMI) were associated with poorer actigraphic sleep measures. Employment, age, and perceived stress were associated with subjective sleep quality. CONCLUSION: Multiple factors were associated with sleep quality in these young women who were sleeping at home. However, the associations differed for subjectively versus actigraphically assessed sleep quality. Actigraphy is feasible for measuring sleep, but multiple recording nights may be needed to obtain reliable estimates.     

No findings of dental defects in children treated with minocycline

Forty-one children <8 years of age treated for brucellosis with oral minocycline (2.5 mg/kg) twice daily for 3 weeks were recalled and examined to check for dental staining and defects. Dental staining and defects were found in 14 of 41 exposed children (34.1%) and in 30 of 82 matched controls (36.6%), respectively (P > 0.2).     

A chimeric peptide composed of a dermaseptin derivative and an RNA III-inhibiting peptide prevents graft-associated infections by antibiotic-resistant staphylococci

Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K(4)-S4(1-13)(a) is a 13-residue dermaseptin derivative (DD(13)) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD(13)-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD(13)-RIP and DD(13) were equally effective, and that the chimeric peptide but not DD(13) was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD(13) act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections.     

Role of surface-exposed loops of Haemophilus influenzae protein P2 in the mitogen-activated protein kinase cascade

The outer membrane of gram-negative bacteria contains several proteins, and some of these proteins, the porins, have numerous biological functions in the interaction with the host; porins are involved in the activation of signal transduction pathways and, in particular, in the activation of the Raf/MEK1-MEK2/mitogen-activated protein kinase (MAPK) cascade. The P2 porin is the most abundant outer membrane protein of Haemophilus influenzae type b. A three-dimensional structural model for P2 was constructed based on the crystal structures of Klebsiella pneumoniae OmpK36 and Escherichia coli PhoE and OmpF. The protein was readily assembled into the beta-barrel fold characteristic of porins, despite the low sequence identity with the template proteins. The model provides information on the structural features of P2 and insights relevant for prediction of domains corresponding to surface-exposed loops, which could be involved in the activation of signal transduction pathways. To identify the role of surface-exposed loops, a set of synthetic peptides were synthesized according to the proposed model and were assayed for MEK1-MEK2/MAPK pathway activation. Our results show that synthetic peptides corresponding to surface loops of protein P2 are able to activate the MEK1-MEK2/MAPK pathways like the entire protein, while peptides modeled on internal beta strands are unable to induce significant phosphorylation of the MEK1-MEK2/MAPK pathways. In particular, the peptides corresponding to loops L5 (Lys206 to Gly219), L6B (Ser239 to Lys253), and L7 (Thr280 to Lys287) activate, as the whole protein, essentially JNK and p38.