Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF.

This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.     

Chlorhexidine in Cleft Lip and Palate Patients with Multibracket Appliances

AIM: The aim of this study is to reduce the caries risk in cleft lip and palate (CLP) patients with multibracket appliances via a compliance-independent method. PATIENTS, MATERIALS AND METHODS: Sixty-eight CLP patients with multibracket appliances were submitted to professional tooth cleaning at 4-week intervals. After randomization, patients in group A wore a splint filled with chlorhexidine (CHX) gel (Chlorhexamed) for 15 minutes (3 x 5 min) every 12 weeks. Patients in group B were treated with CHX varnish (EC40) every 12 weeks. Fluoride varnish (Fluoridin) was applied to all teeth 4 and 8 weeks after the respective CHX treatments. Regular salivary bacteria counts (CRT) were carried out to determine therapeutic effectiveness. Initial DMFS values were compared to the final ones. RESULTS: Initial findings of the salivary test and DMFS index confirmed the high caries risk. The DMFS value increased dramatically in both groups despite this systematic prophylaxis program. The bactericidal effect of both CHX preparations turned out to be markedly weaker than that described in the literature. CONCLUSIONS: Though the CHX and fluoride application had a limited effect (at least in this test population), one should keep in mind that it is precisely this population that requires very intensive prophylaxis, and that no antibacterial adjuvant is more effective than CHX. However, the application interval should be individually adapted to the bacteria count.     

Potential of a new cw 2 μm laser scalpel for laparoscopic surgery

The potential of a new continuous-wave (cw) thulium–YAG laser for laparoscopic small intestine resection was investigated in pigs in comparison to standard bipolar scissors.

Method

A diode-pumped solid-state thulium–YAG laser system emitting at a wavelength of 2.01 μm was used. Laser power up to 25 W in cw mode was transmitted via a quartz fibre (400 μm core diameter). In order to resect 1 m of the small intestine, the accompanied mesentery was dissected with both devices in 12 pigs (six each group). Arteries and veins of 0.25–3.2 mm inner diameter were dissected in vivo and the resistance of the occluded vessels to pressures up to 375 mmHg was measured by an in vitro set-up. Samples were prepared for histological evaluation.

Results

With respect to intestine resection with bipolar scissors, bleeding occurred significantly less (25%) and dissection time was reduced by 19% using the 2 μm laser scalpel. With the 2 μm laser scalpel, small vessels (<0.5 mm) were successfully occluded up to 100% (arteries) and 89% (veins), larger vessels (1–2.3 mm) to 74% (arteries) and 65% (veins) in vivo. In the in vitro pressure measurement with 375 mmHg, 30% of veins and 35% of arteries stayed closed. In conclusion, the first experiments show that the 2 μm laser scalpel is a promising dissection device for minimally invasive surgery.     

Kidney failure in Townes-Brocks syndrome: an under recognized phenomenon?

Though uncommon, kidney malformations are described in several cases of Townes-Brocks syndrome. By contrast, kidney failure has been reported as the presenting feature of Townes-Brocks syndrome on only one occasion. While the SALL1 gene, mutations of which result in the Townes-Brocks phenotype, is expressed in the developing kidney, the absence of other corroborative reports of kidney failure presenting in affected individuals suggests that the solitary observation of kidney failure is as likely due to chance as to causal association. In now reporting a further instance of this association, we review the literature, demonstrating that several other instances of kidney failure are in fact known, despite an incomplete dataset. These findings suggest that kidney failure may be a constituent element of the natural history of Townes-Brocks syndrome and raise the possible benefits of longitudinal survey for progressive kidney impairment in patients with this syndrome.     

Fifteen years of env C2V3C3 evolution in six individuals infected clonally with human immunodeficiency virus type 1

The study of the evolution of human immunodeficiency virus type 1 (HIV-1) requires blood samples collected longitudinally and data on the approximate time point of infection. Although these requirements were fulfilled in several previous studies, the infectious sources were either unknown or heterogeneous genetically. In the present study, HIV-1 env C2V3C3 (nt 7029-7315) evolution was examined retrospectively in a cohort of hemophiliacs. Compared to other cohorts, the area of interest here was the infection of six hemophiliacs by the same virus strain, that is, the infecting viruses shared an identical genome. As expected, divergence from the founder sequence as well as interpatient divergence of the predominant virus strains increased significantly over time. Based on the V3 nucleotide sequences, CCR5 usage was predicted exclusively throughout the whole period of infection in all patients. Interestingly, common patterns of viral evolution were detected in the patients of the cohort. Four amino acid substitutions within the V3 loop emerged and persisted subsequently in five (positions 305 and 308 of the HXB2 gp120 reference sequence) and six patients (positions 325 and 328 in HXB2 gp120), respectively. These common changes within the V3 loop are likely to be enforced by HIV-1 specific immune response.     

Water sorption and solubility of contemporary resin-based filling materials

PURPOSE: Evaluation of water sorption and solubility of contemporary resin-based filling materials. METHODS: Specimens of Herculite (HE), Point 4 (P4), TetricCeram (TC), Miris (MI), TetricCeram HB (HB), Solitaire 2 (SO), SureFil (SU), Definite (DE), Admira (AD), Dyract AP (DY), Compoglass F (CO), and TetricFlow (TF) were prepared according to ISO 4049. Water sorption and solubility were measured after water storage at 37 degrees C for 7 days. RESULTS: Water sorption was HE 14 microg mm(-3), P4 17 microg mm(-3), TC 12 microg mm(-3), MI 13 microg mm(-3), HB 9 microg mm(-3), SO 18 microg mm(-3), SU 9 microg mm(-3), DE 14 microg mm(-3), AD 27 microg mm(-3), DY 19 microg mm(-3), CO 23 microg mm(-3), and TF 19 microg mm(-3). Solubility was HE 3 microg mm(-3), P4 3 microg mm(-3), TC 1 microg mm(-3), MI 0 microg mm(-3), HB 0 microg mm(-3), SO 3 microg mm(-3), SU 0 microg mm(-3), DE 1 microg mm(-3), AD 2 microg mm(-3), DY 4 microg mm(-3), CO -2 microg mm(-3), and TF 1 microg mm(-3). CONCLUSION: All materials met the corresponding requirement in ISO 4049. Filler load negatively correlated with water sorption but not with solubility. There was an influence of the resin matrix, too. No significant differences were found between composites, ormocers, and compomers.     

Myoglobin plasma level related to muscle mass and fiber composition – a clinical marker of muscle wasting?

Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p < 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.     

2nd-generation HIV surveillance and injecting drug use: uncovering the epidemiological ice-berg

Summary Objectives: HIV/AIDS surveillance methods are under revision as the diversity of HIV epidemics is becoming more apparent. The so called “2^nd generation surveillance (SGS) systems” aim to enhance surveillance by broadening the range of indicators to prevalence, behaviors and correlates, for a better understanding and a more complete and timely awareness of evolving epidemics. Methods: Concepts of HIV SGS are reviewed with a special focus on injecting drug users, a major at-risk and hard to reach group in Europe, a region with mainly low or concentrated epidemics. Results: The scope of HIV/AIDS surveillance needs to be broadened following principles of SGS. Specifically for IDUs we propose including hepatitis C data as indicator for injecting risk in routine systems like those monitoring sexually transmitted infections and information on knowledge and attitudes as potential major determinants of risk behavior. Conclusions: The suggested approach should lead to more complete and timely information for public health interventions, however there is a clear need for comparative validation studies to assess the validity, reliability and cost-effectiveness of traditional and enhanced HIV/AIDS surveillance systems. Submitted: 24 October 2005; Revised: 19 June 2006; Accepted: 5 October 2006