Foix-Chavany-Marie-syndrome — neurological,neuropsychological, CT,MRI, and SPECT findings in a case progressive for more than 10 years

Summary In a 66-year-old woman signs and symptoms of bilateral opercular syndrome (Foix-Chavany-Marie-syndrome) developed progressively over a period of more than 10 years. Facio-linguo-velo-pharyngeo-masticatory diplegia with automatic-vol-untary dissociation was accompanied by motor aphasia and oral apraxia leading to a state of almost complete anarthria. Although it initially resembled the anterior biopercular syndrome there are also features indicating involvement of the posterior opercula. Although the aetiology remains obscure without pathological data, a bilateral focal brain atrophy is assumed. This is probably the first case documented by MRI and SPECT.Supported by the Hirnliga, Heidelberg, Federal Republic of Germany     

Piezoelectric shock wave lithotripsy of salivary gland stones: an in vitro feasibility study

The feasibility of fragmentation of salivary stones by a new extracorporeal piezoelectric lithotripter was investigated. A total of 40 salivary stones were submitted to piezoelectric shock wave treatment. The diameter, weight, and volume of all the stones were determined prior to shock wave administration. After shock wave administration the chemical composition of the stones was investigated by X-ray diffractometry. Fragmentation was achieved in 35 out of the 40 (87.5%) stones. Twenty-five of the 40 (62.5%) stones were disintegrated "therapeutically adequate" (residual fragments less than 1.5 mm). A statistically significant correlation was not observed between the number of discharges required for disintegration and the diameter, weight, volume, or the chemical composition of the stones.     

Cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells as compared to connective tissue fibroblasts

The cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells cloned from the hypopharynx (FaDu) and benign connective tissue cells (fibroblasts) were investigated in vitro. Sonication was carried out using an experimental piezoelectric, self-focusing burst-signal transducer. To increase the induction of cavitation, the transducer used was specifically designed to produce multiple oscillations with a high negative pressure amplitude. In both cell lines tested, the application of 100, 800 and 2000 pulses resulted in a high reduction of vital cells. After 2000 pulses, 4.0 ± 1.1% of the fibroblasts but only 2.0 ± 0.4% of the FaDu cells survived HEPUS exposure. A postexposure inhibiting effect of HEPUS for 10 days on the proliferation of surviving cells was noted for the FaDu cells exposed to 2000 pulses, but not as much for the fibroblasts. These findings support the hypothesis that human squamous cell carcinoma cells of the hypopharynx might be more sensitive to HEPUS than fibroblasts and that total tumor cell ablation might be possible in vitro given a sufficient number of HEPUS pulses. Received: 18 November 1997 / Accepted: 21 April 1998     

Effect of intravenous nitroglycerin on lipid peroxidation after thrombolytic therapy for acute myocardial infarction

Free oxygen radicals are produced after coronary artery occlusion and reperfusion. Polyunsaturated fatty acids are oxidized by free radicals to lipid peroxides. Measurements of plasma malondialdehyde (MDA) formed by the breakdown of lipid peroxides are often used as markers of lipid peroxidation. The effect of intravenous nitroglycerin on plasma MDA levels was studied in 43 patients who received thrombolytic therapy for acute myocardial infarction. Plasma MDA levels in patients were elevated on admission to the hospital compared with healthy controls, and normalized within 48 hours. A greater increase in plasma MDA concentrations after thrombolysis was found in patients with noninvasive signs of reperfusion than in patients judged to have a persistent occlusion. In the 23 patients receiving immediate intravenous nitroglycerin infusion, plasma MDA levels did not change from baseline to 90 minutes (0.92 ± 0.22 and 0.92 ± 0.23 μmol/L, p = 0.99), whereas a significant increase was found in the 20 control patients who did not receive nitroglycerin (from 0.83 ± 0.22 to 1.01 ± 0.30 μmol/L, p = 0.0004) (p = 0.036 for the difference between groups). Successful reperfusion after thrombolytic therapy entails increased lipid peroxidation. Intravenous nitroglycerin reduces lipid peroxidation during myocardial ischemia and reperfusion.     

In Vitro Activity of wALADin Benzimidazoles against Different Life Cycle Stages of Plasmodium Parasites

wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.     

Direct observation of prefreezing at the interface melt–solid in polymer crystallization

Crystallization is almost always initiated at an interface to a solid. This observation is classically explained by the assumption of a reduced barrier for crystal nucleation at the interface. However, an interface can also induce crystallization by prefreezing (i.e., the formation of a crystalline layer that is already stable above the bulk melting temperature). We present an atomic force microscopy (AFM)-based in situ observation of a prefreezing process at the interface of a polymeric model system and a crystalline solid. Explicitly, we show an interfacial ordered layer that forms well above the bulk melting temperature with thickness that increases on approaching melt–solid coexistence. Below the melting temperature, the ordered layer initiates crystal growth into the bulk, leading to an oriented, homogeneous semicrystalline structure.The fundamental process of crystallization from the liquid or gaseous state is of importance in many areas of condensed matter physics and materials science. In practice, crystallization is, in most cases, initiated at an interface to a solid. Crystal growth on solid substrates from the gaseous state has been studied in depth, and detailed understanding of different growth modes as well as interfacial thermodynamics has been achieved (1–3). Much less experimental data are available for crystallization occurring at the interface from the solid to the melt. Generally, crystallization can be initiated at the solid–melt interface by two processes: heterogeneous nucleation or formation of a crystalline wetting layer (so-called prefreezing) (4–6). In terms of thermodynamics, these processes are very different. Whereas nucleation takes place under nonequilibrium conditions at finite supercooling below the melting temperature T_m of the bulk material, the formation of a wetting layer is an equilibrium phenomenon taking place above T_m (4). It is often assumed that heterogeneous nucleation is the more relevant process (7), but in simulations, nucleation as well as prefreezing have been shown to occur (4, 8). Prefreezing is expected for strongly attractive surfaces or epitaxial systems for which the lattices of the substrate and the crystallizing materials match well (9–12). In the case of polymers, prefreezing can also manifest itself in the conformational degrees of freedom, leading to an interfacial layer with nematic order, which was recently shown in simulations (13). Because of the difficult accessibility of the buried interface between a melt and a solid, direct observation of crystallization of molecular systems at the interface is lacking, and there is only limited, indirect evidence that, in some cases, prefreezing at the solid interface exists (e.g., for the growth of aluminum crystals on TiB₂ particles) (14, 15). Recently, it has been suggested that prefreezing also plays a role during epitaxial crystallization in some polymeric systems (16). It is well-known, however, that one or sometimes several ordered layers of organic molecules can form on suitable substrates at temperatures above the bulk melting point, which was observed for, for example, alkanes or similar molecules on graphite by scanning tunneling microscopy (17), atomic force microscopy (AFM) (18–20), or scattering methods (21, 22; review in ref. 23). A related but more special phenomenon is surface freezing of liquids (22). In some liquids, an ordered monolayer forms at the free surface in a finite temperature range above the bulk melting temperature [e.g., alkanes (24), alkylated side chain polymers (25), and AuSi alloys (26)]. It is an open question, however, which exact role all of these structures play for the initiation of crystal growth (27) and in most cases, the temperature range around melt–solid coexistence, where crystallization starts has not been studied in detail. Only for colloidal model systems has crystallization by prefreezing been directly observed (28) and studied in simulations (8, 10, 11).We here present direct AFM observations of an ordered wetting layer at the interface to a solid close to coexistence of the solid and the liquid phases of a polymeric model system. We show evidence for a temperature-dependent thickness of the wetting layer and its disappearance at a prewetting transition at finite superheating above T_m. Our observations are in line with a divergence of the layer thickness at the bulk melting temperature as expected for complete wetting. Below T_m, crystal growth into the film is initiated by the interfacial layer.     

Biomarkers for Type 2 Diabetes and Impaired Fasting Glucose Using a Nontargeted Metabolomics Approach

Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10⁻⁹) and was moderately heritable (h² = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10⁻⁶) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10⁻³). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication.     

Outcomes of transoral laser microsurgery and transoral robotic surgery in oropharyngeal squamous cell carcinoma

ObjectiveTransoral robotic surgery (TORS) has evolved to a standard therapy modality for oropharyngeal carcinoma, especially in T1/ T2 tumors involving the base of the tongue due to its advantages compared with open surgery. However, knowledge about its benefits compared with transoral laser microsurgery (TLM) are scarce. This study compares oncological and functional results of TLM or TORS in the treatment of oropharyngeal squamous cell carcinoma (OPSCC).MethodsThis retrospective analysis comprises all patients with OPSCC treated with TLM (n = 30) or TORS (n = 24) between April 2003 and May 2018 (follow-up 43 ± 38.3 months). Both treatment groups (TLM and TORS) were comparable in terms of the stage of the disease, prognosis-determining factors, and adjuvant therapy modalities.ResultsThere were no significant differences regarding to the resection status (p = 0.272), the rate of local- (p = 0.834) and distant- recurrence (p = 0.416), with a disease-free survival of 86.7 % and 87.5 %, respectively (p = 0.892). In addition, we could not confirm any differences regarding to operating time (p = 0.860), intraoperative blood loss (p = 0.660), inpatient stay (p = 0.585) and postoperative bleeding rate (p = 0.245). The frequency of tracheostomy and percutaneous endoscopic gastrostomy between both groups is comparable, with a longer duration of tube feeding in patients who have received TLM (p = 0.030).ConclusionIn conclusion, TORS allows for similar oncological outcomes compared with TLM at comparable perioperative risks. The postoperative swallowing function may benefit from TORS.