Therapist-aided exposure for women with lifelong vaginismus: A replicated single-case design.

Vaginismus is commonly described as a persistent difficulty in allowing vaginal entry of a penis or other object. Lifelong vaginismus occurs when a woman has never been able to have intercourse. A replicated single-case A-B-phase design was used to investigate the effectiveness of therapist-aided exposure for lifelong vaginismus. A baseline period (Phase A) was contrasted with exposure + follow-up (Phase B), using random switching between phases. The main outcome measure (intercourse ability) was assessed daily for 24 weeks. Ten women participated. The exposure consisted of a maximum of three 2-hr sessions during 1 week at a university hospital. The participant performed vaginal penetration exercises on herself, in the presence of a female therapist. Two follow-up sessions were scheduled over a 5-week period. Nine of the 10 participants reported having intercourse after treatment, and in 5 of the 9, intercourse was possible within the 1st week of treatment. The results remained at 1-year follow-up. Furthermore, exposure was successful in decreasing fear and negative penetration beliefs posttreatment and at 3-month and 1-year follow-ups. Therapist-aided exposure appears to be an effective treatment for lifelong vaginismus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmaceutical development of a parenteral lyophilized formulation of the investigational polymer-conjugated platinum anticancer agent AP 5280

AP 5280 is a novel polymer-conjugated platinum anticancer agent showing promising in vitro and in vivo activity against solid tumors. The aim of this study was to develop a parenteral pharmaceutical dosage form for phase I clinical trials. AP 5280 drug substance was characterized by using a wide range of analytical techniques and showed excellent solubility in water. However, as aqueous solutions of AP 5280 proved to be labile upon sterilization by moist heat, it was decided to develop a lyophilized dosage form. Initially, glass vials were used as primary packaging, but this led to a high breakage rate, which could be completely prevented by the use of CZ® resin vials. Stability studies to date show that the lyophilized product in glass vials is stable for at least 12 months when stored at 2-8°C in the dark and the lyophilized product in CZ resin vials is stable for at least 6 months under these conditions. Photostability testing revealed photolability of AP 5280 drug substance and lyophilized product in both types of primary container, necessitating storage in the dark. The first clinical experiences indicate that the proposed formulation is fully applicable for use in the clinical setting.     

A fast-settling CMOS op amp for SC circuits with 90-dB DC gain

A technique that combines the high-frequency behavior of a single-stage op amp with the high DC gain of a multistage design is presented. This technique is based on the concept that a very high DC gain can be achieved in combination with any unity-gain frequency achievable by a (folded-) cascode design. Bode-plot measurements for an op amp realized in a 1.6-μm process show a DC gain of 90 dB and a unity-gain frequency of 116 MHz (16-pF load). Settling measurements with a feedback factor of 1/3 show a fast single-pole settling behavior corresponding to a closed-loop bandwidth of 18 MHz (35-pF load) and a settling accuracy better than 0.03%. This technique does not cause any loss in output voltage swing. At a supply voltage of 5.0 V an output swing of about 4.2 V is achieved without loss in DC gain. The above advantages are achieved with a 30% increase in chip area and a 15% increase in power consumption     

The ultrapurification of tellurium

High-purity tellurium is used in the preparation of II–VI compounds, particularly CdTe and Cd_x Hg_1?x Te. Distillation of tellurium under low-pressure H₂ reduces the concentrations of iron and silicon. The addition of CdTe to tellurium prior to zone refining, in a quantity less than the eutectic concentration, has been observed to change the segregation behavior of Ca, K, Ga and As, which enables more efficient refining. Emission spectroscopy, spark source mass spectroscopy and the evaluation of Cd_0.21Hg_0.79 Te have been used to characterize these effects.     

A 21-mW 8-b 125-MSample/s ADC in 0.09-mm/sup 2/ 0.13-/spl mu/m CMOS

This paper presents an 8-b two-step subranging analog-to-digital (ADC) using interpolation, averaging, offset compensation, and pipelining techniques to accomplish an effective number of bits of 7.6 b at 125 MSample/s. The 0.13-/spl mu/m CMOS ADC occupies 0.09 mm/sup 2/ and consumes 21 mW.     

Design and analysis of CMOS analog signal processing circuits bymeans of a graphical MOST model

A graphical representation of a simple MOST (metal-oxide-semiconductor transistor) model for the analysis of analog MOS circuits operating in strong inversion is given. It visualizes the principles of signal-processing techniques depending on the characteristics of an MOS transistor. Several linearization techniques as well as a multiplying principle become transparent at the hand of the graphical representation. In the examples, special attention is focused on continuous-time filter techniques. The basis of MOSFET-C continuous-time filters and CMOS square-law circuits are explained using the graphical MOST characteristics representation     

No evidence for a Y chromosomal effect on alternative behavioral strategies in mice

This study takes the first step toward testing a Y chromosomal effect on both aggression and thermoregulatory nest-building behavior in mouse lines either bidirectionally selected for short (SAL) and long (LAL) attack latency or high (HIGH) and low (LOW) nest-building behavior. Using reciprocal crosses between SAL and LAL, and between HIGH and LOW, we found no indications for Y chromosomal effects on thermoregulatory nest-building behavior. As for aggression, we confirmed earlier studies on SAL and LAL, i.e., the origin of the Y chromosome influences attack latency, i.e., aggression. However, we did not find indications for a Y chromosomal effect on aggression in the HIGH and LOW lines. Since aggression and nest-building behavior have been shown to be characteristic parameters of two fundamentally different behavioral strategies, the present data underline the improbability of Y chromosomal genes underlying the genetic architecture of alternative behavioral strategies.     

Apoptosis and related proteins in different stages of human atherosclerotic plaques

BACKGROUND: The transition of a fatty streak into an atherosclerotic plaque is characterized by the appearance of focal and diffuse regions of cell death. We have investigated the distribution of apoptotic cell death and apoptosis-related proteins in early and advanced atherosclerotic lesions. METHODS AND RESULTS: Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy specimens (n=18). This approach allowed comparison of adaptive intimal thickenings, fatty streaks, and advanced atherosclerotic plaques of the same patient. The fatty streaks differed from adaptive intimal thickenings by the presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both regions were composed mainly of smooth muscle cells (SMCs), and macrophage infiltration was low and not different. Apoptosis, as detected by DNA in situ end labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ nick translation) was not present in these regions. Apoptosis of SMCs and macrophages, however, was present in advanced atherosclerotic plaques that were present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/-3% surface area) was present in these advanced atherosclerotic plaques. Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal lamina, were TUNEL negative and remained present in the plaques as matrix vesicles. CONCLUSIONS: We conclude that SMCs within human fatty streaks express BAX, which increases the susceptibility of these cells to undergo apoptosis. The localization of these susceptible SMCs in the deep layer of the fatty streaks could be important in our understanding of the transition of fatty streaks into atherosclerotic plaques, which are characterized by regions of cell death. Matrix vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can calcify and may be considered the graves of SMCs that have died in the plaques.     

The role of prostaglandin E2 and nitric oxide in cell death in J774 murine macrophages

We investigated the role of prostaglandin E2 (PGE2) and its interactions with nitric oxide (NO) on cell death and NO-mediated cytotoxicity in the murine macrophage cell line J774. Stimulation of the J774 cells with lipopolysaccharide together with interferon-gamma resulted in a dose-dependent cytotoxicity and production of PGE2 and NO, measured as nitrite. Our results showed a linear correlation between PGE2 release and cytotoxicity. The cyclooxygenase (COX) inhibitor indomethacin completely inhibited PGE2 biosynthesis, without affecting NO production or cell death. This supports previous reports suggesting that overproduction of endogenous PGE2 is mainly the consequence of cell death and does not cause it. In contrast, the NO synthase inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) gave a significant, though incomplete suppression of NO release and cell death. This points to the presence of other cytotoxic factors besides NO. To evaluate the toxic effect solely due to NO, macrophages were exposed to the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Incubation with SNAP also resulted in a concentration-dependent cell injury and PGE2 production. When exogenously added, PGE2 protected against SNAP-mediated cytotoxicity and simultaneously increased PGE2 release into the medium, without inducing COX-2. The cytoprotection and the stimulation of PGE2 release were both reversed by indomethacin. In conclusion, PGE2 biosynthesis may represent a mechanism by which inflammatory macrophages protect themselves against the cytotoxic effects of NO.     

Degradation kinetics of three gonadorelin analogues: developing a method for calculating epimerization parameters

PURPOSE: To develop a method for calculating epimerisation parameters, find out if the kinetics of the independent reactions can be established, and elucidate primary structure-chemical degradation relationships in the degradation kinetics of three gonadorelin analogues. METHODS: The influences of pH, temperature, and buffer concentration on the degradation of the three gonadorelin analogues buserelin, goserelin, and triptorelin were investigated using RP-HPLC. A method was developed to calculate epimerisation and hydrolysis rate constants independently. RESULTS: Explicit structure-degradation mechanism relations were found in the degradation of all three compounds. The L-serine residue was found to be involved in both a solvent-catalysed backbone hydrolysis and a hydroxyl-catalysed epimerisation whereas, the O-tertiary butyl D-serine residue was only involved in proton-catalysed ether hydrolysis. The kinetics of identical reactions in different analogues were generally comparable. CONCLUSIONS: The degradation of the gonadorelin analogues is located at a relatively small number of chemical residues and prediction of the degradation mechanisms and kinetics of other peptides with similar structural elements appears to be possible.