Clostridium perfringens Septicemia and a Bleeding Ulcer of a Jejunal Interposition: A Case Report and Short Review of the Literature.

INTRODUCTION: We report a case of Clostridium perfringens septicemia in a patient presenting with a bleeding ulcer of a jejunal interposition. CASE PRESENTATION: An 81-year-old female patient was acutely admitted to our hospital due to hematemesis and melena. She had a history of metastatic gastrointestinal stromal tumor, for which she was receiving second line treatment with sunitinib. She had also undergone a Merendino procedure 4 years prior to presentation. The patient underwent emergency gastroscopy, which revealed a bleeding ulcer in the jejunal interposition. Despite initial endoscopic control of the bleeding and transfusion of blood products, the hemoglobin level continued to drop, and the patient was treated for an assumed hemolytic transfusion reaction. The patient died 3 days following admission, and the results of blood cultures later confirmed a Clostridium perfringens septicemia. The postmortem examination revealed a diffuse spread of Clostridium perfringens to multiple organs. CONCLUSION: This case is a reminder of the importance of considering septicemia, particularly in association with Clostridium perfringens, as a potential cause of hemolysis. It also demonstrates the extent of organ involvement in a case of diffuse clostridial myonecrosis.

Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

[Thermography of the skin covering a cochlear implant--temperature as an indicator for blood circulation]. / Thermographische Untersuchungen zur Durchblutungssituation der ein Cochlear Implant bedeckenden Haut.

BACKGROUND: Sufficient blood supply of the flap is a significant factor for proper wound healing and lifelong integration of a cochlear implant. Superficial temperature as an indicator of cutaneous blood circulation can be visualized easily by thermography. QUESTION: We examined the correlation between temperature distribution and the anatomic course of defined arteries, the significance of different types of incisions in this regard, and local irritations of skin temperature/blood circulation by the implant itself. MATERIALS AND METHOD: The partially shaved heads of 15 patients were examined by thermography after cochlear implantation, using the Agema thermovision system. RESULT: Temperature distribution of the skin can be closely related to the arterial blood supply. In our group of patients, no significant alterations could be found in the skin covering the implant. Hair growth in the area tested does not allow valid thermographies. DISCUSSION: By the pattern of temperature-distribution/blood circulation some conclusions about typical incisions can be drawn. While most types of incisions respect the patterns of blood circulation, the retroauricular C-incision may cause problems. Postoperative scars can be regarded as places of minor resistance. CONCLUSIONS: Thermography of the skin is an easy method for estimating the blood circulation of the skin above the implant. It is, however, limited to hair-free or shaved skin areas.

Pharmacokinetics and disposition of a novel NMDA glycine site antagonist (UK-240,455) in rats, dogs and man.

1. UK-240,455 ((+) 6,7-dichloro-5-[N-(2-hydroxyethyl)methanesulphonamido]-2,3 (1H,4H)-quinoxalinedione) is a potent, selective N-methyl D-aspartate (NMDA) glycine site antagonist that is being evaluated for the potential treatment of stroke. 2. UK-240,455 is predominately excreted unchanged in urine (58-68%) in rats, dogs and man following intravenous administration. The remainder of the dose is excreted unchanged in the faeces. It is considered that UK-240,455 is predominantly cleared by active renal tubular secretion and active hepatobiliary transport. In man, there is evidence that UK-240,455 undergoes glucuronidation. However, there is no evidence for this in rats and dogs. 3. UK-240,455 has a short elimination half-life in rats, dogs and man (0.4-1.4 h) and clearances of 12, 13 and 6 ml min(-1) kg(-1), respectively. The compound shows limited tissue distribution with volumes of distribution of 0.4-0.8 l kg(-1) in rats, dogs and man. The species' variation in pharmacokinetic parameters was related allometrically when plasma protein binding was taken in to account. Hence, active hepatic or renal clearance processes for this compound were conserved across species. 4. Cerebrospinal fluid and brain concentrations of UK-240,455 were determined in rats. The cerebrospinal fluid/plasma concentration ratio of UK-240,455 was 4.3%, which was similar to the plasma-free fraction of this compound (3%), indicating good blood-brain barrier permeability. Brain tissue concentrations were low (0.7% of the total plasma concentrations).

Heat radiation during caloric vestibular test: thermographic demonstration in temporal bone experiments.

Since Barany's descriptions in 1906, cold and warm irrigations of the external ear canal have been used for unilaterally testing vestibular excitability. The fluid kinetics within the endolymph have been studied thoroughly, whereas relatively few published articles deal with the mechanisms of heat transfer from the external to the internal ear. Even though heat conduction via the bone seemed to be well established in the textbooks, Feldmann and co-workers found heat radiation to be a very important factor. Using a rather uncommon method, we tried to make this heat radiation more apparent: in temporal bone experiments, temperature distribution was followed by thermography. Temporal bone specimens were prepared in such a way that heat distributions became visible after experimental caloric irrigations of the external ear canal. Temperature changes could well be verified by changes in coloration of the 2-dimensional thermograms. Conclusions were drawn from registrations performed in 2 projections, 90 degrees to each other, allowing cautious statements about 3-dimensional distribution. The velocity of heat transfer at the very onset of the reaction can only be explained by radiation, whereas later, other mechanisms, such as conduction via the bone or convection via the middle ear gas, may have some influence. Our results support Feldmann's findings and underline the significance of radiation in the heat transfer mechanism.

[Vertigo in suction of open mastoid cavities ("radical surgery cavities")]. / Untersuchungen zum Schwindel beim Absaugen von offenen Mastoidhöhlen ("Radikalhöhlen").

BACKGROUND: Vertigo during suction-cleaning of open mastoid cavities is caused by cold stimulation of the vestibular organ. In clinical and model-experimental measurements we tried to estimate the physical background and the dimension of this temperature drop. METHODS: Using different techniques like thermo-probes, thermovision, or additional model experiments temperature changes during suction were measured in 5 volunteers with open mastoid cavities. These registrations were carried out with special regard to the moisture of the cavity-walls. RESULTS: Distinct temperature changes during suction were observed. In moist cavities superficial temperature decrease was much higher than in dry ones. Using additional model experiments, temperature conduction towards e.g. the horizontal semicircular canal could be simulated. DISCUSSION AND CONCLUSIONS: Among other mechanisms like replacement of sucked-off air by colder air, or taking away warm air close to the cavity walls, effects of evaporative cold seem to be very significant. This could be demonstrated by moistening cavity walls in patients as well as in model experiments. The conclusion to keep the cavity walls as dry as possible is already a clinical demand. In this paper, the physical background and the dimensions of thermal effects during suction-cleaning could be elucidated.

The mutated human gene encoding hepatocyte nuclear factor 1beta inhibits kidney formation in developing Xenopus embryos.

The transcription factor hepatocyte nuclear factor 1beta (HNF1beta) is a tissue-specific regulator that also plays an essential role in early development of vertebrates. In humans, four heterozygous mutations in the HNF1beta gene have been identified that lead to early onset of diabetes and severe primary renal defects. The degree and type of renal defects seem to depend on the specific mutation. We show that the frameshift mutant P328L329fsdelCCTCT associated with nephron agenesis retains its DNA-binding properties and acts as a gain-of-function mutation with increased transactivation potential in transfection experiments. Expression of this mutated factor in the Xenopus embryo leads to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects are generated by overexpressing in Xenopus the wild-type HNF1beta, which is consistent with the gain-of-function property of the mutant. In contrast, introduction of the human HNF1beta mutant R137-K161del, which is associated with a reduced number of nephrons with hypertrophy of the remaining ones and which has an impaired DNA binding, shows only a minor effect on pronephros development in Xenopus. Thus, the overexpression of both human mutants has a different effect on renal development in Xenopus, reflecting the variation in renal phenotype seen with these mutations. We conclude that mutations in human HNF1beta can be functionally characterized in Xenopus. Our findings imply that HNF1beta not only is an early marker of kidney development but also is functionally involved in morphogenetic events, and these processes can be investigated in lower vertebrates.

[Thermographic detection of heat radiation in caloric vestibular function tests]. / Thermographischer Nachweis der Wärmestrahlung bei der kalorischen Vestibularisprüfung.

BACKGROUND: Since Bárány; caloric irrigations in the external ear canal have been used for unilateral stimulation of the peripheral vestibular system. However, the mechanism of heat transfer from the auditory canal to the vestibular organ is not completely known. From the physical point of view, three mechanisms may be discussed: heat conduction via the bone, convection via the middle ear gas, or radiation. Feldmann et al. (1991) singled out radiation as a very important factor in this regard. Using high-resolution thermography, we were able to "see" radiation almost directly in temporal bone experiments. METHODS: Using the system of infrared thermovision specially adapted for close-up studies, the effect of calorization can be observed and documented in colored planar thermograms. Fresh temporal bone specimens had to be prepared so as to permit simultaneous observation of the tympanic membrane and the medial tympanic wall. RESULTS: Changes in temperature were readily visible during experimental caloric tests: turning blue indicated cooling and red indicated warming. In the caloric test with 44 degrees C or 30 degrees C water, changes in color of the eardrum appeared immediately. At the very same time, however, an area of the medial tympanic wall also changed color. This velocity of transfer cannot be attained by conduction or convection: heat radiation is the only possible explanation. This could only be demonstrated at the very onset of the reaction; subsequent thermograms became more and more diffuse. In this stage the heat transfer may also be effected by conduction and/or convection. CONCLUSIONS: Thermography demonstrates that radiation is a very important factor in heat transfer; at least in the initial phase of calorization.

Cyclophotocoagulation: experimental investigations of dosage problems.

BACKGROUND: During cyclophotocoagulation, transsclerally applied laser light reduces the aqueous-producing structures of the eye. One problem using this therapy is patient-specific dosage of the applied laser energy. The aim of our investigations was to obtain information about intensity and distribution of tissue destruction in the coagulation area. This may provide a basis for further on-line control of cyclophotocoagulation by ultrasound-controlled engineering of the diode laser. METHODS: To visualize the process of cyclophotocoagulation, a multifunctional measurement set-up was developed. It allowed the visualization of structural changes in the coagulation area using a common light microscope and comparison in the first set-up to the results detected by high-resolution ultrasound, applied in different working modes (B-mode, M-mode and RF signal analyses). In a second set-up an infrared thermography system showing temperature distribution on the scleral surface at the contact point of the laser probe was used. RESULTS: High resolution working in B- and M-mode was unsuitable to visualize structural changes within the therapeutic width. By analyzing RF ultrasound date, structural changes within the therapeutic width could be detected. Surface temperatures measured by infrared thermography correlated with visible structural changes when long exposure times and low laser power were applied. CONCLUSIONS: In certain cases the visualization of coagulation effects was possible with the help of either high-resolution ultrasound or infrared thermography. Spectrum analysis of RF ultrasound signals seems to be a potential method for successful control of cyclophotocoagulation.

Rapid and robust detection of branch points from wave-front gradients.

We discuss a technique that permits branch points in the phase function to be localized in real-time adaptive-optics systems and that is unambiguous and robust in the presence of noise.

Reconstruction of discontinuous light-phase functions.

The reconstruction of discontinuous light-phase functions is of major importance in adaptive optics. An efficient and simple algorithm that can reconstruct large arrays of phases from phase differences is presented. We prove that the algorithm yields a perfect result in the absence of noise, and we describe the function that it maximizes. We suggest a method that makes use of the reconstructed phase to measure the position of branch points. A simulation of the reconstruction of a 33x33 phase array is presented.

Lyapunov stability criteria for zonal adaptive-optics systems.

Lyapunov stability criteria are derived for a first-order closed-loop adaptive-optics servo system, resulting in a linear matrix equation that includes the system geometry, servo parameters, and wave-front reconstruction matrix. It is demonstrated that instability zones depend on the choice of matrix estimator and the servo-loop gain. Divergence of the error propagator gives results that are consistent with the Lyapunov equation. The significance of these results is discussed.

Linear phase retrieval for wave-front sensing.

Phase retrieval from one or more intensity measurements is a potentially powerful and appealing technique for real-time adaptive-optics wave-front sensors. Under the assumption of small wave-front phase excursions, one is able to derive an exact solution to the inverse problem given three or more intensity measurements with known phase offsets. Applications include a high-order wave-front sensor to correct for residual aberrations in an adaptive-optics system in tandem with a low-resolution Hartmann-Shack wave-front sensor. The formula can also furnish mathematical insights into the full nonlinear phase-retrieval task.

[Thermographic study of temperature gradient during ear surgery intervention]. / Thermographische Studie zu Temperaturentwicklungen während ohrchirurgischer Eingriffe.

BACKGROUND: During middle ear surgery manipulations like burring, cooling with water, suction or even screwing cause changes of temperature which should be known to the surgeon. METHOD: An infrared thermovision device was introduced for registration. RESULTS: Thermography is an easy way for continuously recording thermic effects during surgery. If sufficient cooling is guaranteed, no temperatures high enough to cause tissue damage or functional defects could be observed. CONCLUSIONS: Adequate cooling provided, thermal injuries during ear surgery can be neglected. Thermography is an easy method for answering such questions, not only in ear surgery but also in other medical fields.

Rapid, solid phase extraction technique for the high-throughput assay of darifenacin in human plasma.

A novel method has been developed for the rapid solid phase extraction of drugs and metabolites from biological fluids, prior to further analysis. The newly designed, 96-tube micropreparation block facilitates high throughput by enabling the extraction of 96 samples simultaneously. The system is described, linked to HPLC/APCI-MS/MS, for the determination of darifenacin in human plasma. The resulting procedure, using deuterated darifenacin as internal standard, is validated over the concentration range 25-2000 pg/mliter; accuracy (0.6-4.6%) and precision (3.6-18.8%) are considered acceptable and overall recovery was determined to be approximately 50%.

Earth-Based Observations of the Galileo Probe Entry Site

Earth-based observations of Jupiter indicate that the Galileo probe probably entered Jupiter's atmosphere just inside a region that has less cloud cover and drier conditions than more than 99 percent of the rest of the planet. The visual appearance of the clouds at the site was generally dark at longer wavelengths. The tropospheric and stratospheric temperature fields have a strong longitudinal wave structure that is expected to manifest itself in the vertical temperature profile.

Predictive optimal estimators for adaptive-optics systems.

A new class of optimal wave-front estimators for adaptive-optics systems that minimize time-delay errors that are due to atmospheric winds is developed. These matrices utilize the past time history of the servo system by means of temporal Kolmogorov cross-covariance matrices. Except in the simplest case, a nonlinear matrix equation must be iteratively solved. Strehl ratio performance for selected estimators is given.