Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.     

High blood metal ion levels in 19 of 22 patients with metal-on-metal hinge knee replacements

Background and purpose — There has been increasing alarm regarding metal-on-metal (MoM) joint replacements leading to elevated levels of metal ions and adverse reactions to metal debris (ARMDs). There is little information available concerning the prevalence of and risk factors for these adverse reactions, except with MoM hip joint replacements. We determined the levels of metal ions in blood and the rate of revision due to ARMDs in patients treated with MoM hinge total knee arthroplasty (TKA).

Patients and methods — 22 patients with TKAs and MoM hinge connecting mechanisms were studied for whole-blood chromium and cobalt levels at 6 months, 1 year, and/or ≥2 years after surgery. Possible ARMDs were investigated by MRI. 12 patients with TKAs and metal-on-polyethylene (MoP) connecting mechanisms served as controls.

Results — The cobalt levels were over 5?ppb in 19 of the 22 patients in the MoM group and in 1 of the 12 patients in the MoP group. The chromium levels were over 5?ppb in 11 of the 22 patients in the MoM group and in none of the 12 patients in the MoP group. Pseudotumors were operated in 4 of the 22 patients in the MoM group and in none of the patients in the MoP group.

Interpretation — Our results clearly show that the MoM hinge TKA carries a high risk of increased levels of systemic metal ions and also local ARMD, leading to complicated knee revisions. We therefore discourage the use of MoM hinge TKA.     

Perfusion in free breast reconstruction flap zones assessed with positron emission tomography

The aim of this pilot study was to determine the postoperative blood perfusion (BF(PET)) and perfusion heterogeneity (BF(PET) HG) in free microvascular breast reconstruction flap zones with positron emission tomography (PET). Regional BF(PET) and BF(PET) HG of the adipose tissue in medial, central, and lateral parts of 13 free flaps were assessed on the first postoperative morning with PET using oxygen-15-labeled water ([(15)O]H(2)O) in 12 patients undergoing breast reconstruction with a deep inferior epigastric perforator (DIEP) or a transverse rectus abdominis muscle (TRAM) flap. The mean BF(PET) values did not differ between DIEP and TRAM flaps (P = 0.791). The mean BF(PET) values were higher in zone III compared with zone I (P = 0.024). During follow-up, fat necrosis was identified in three patients in the medial part (zone II) of the flap. However, the adipose tissue BF(PET) assessed on the first postoperative day from all zones of the flap using PET with radiowater was normal. The BF(PET) HG was higher in the control side (i.e., in the healthy breast tissue) compared with the flap (P = 0.042). The BF(PET) HG was lower in zone III than in zone I (P = 0.03) and in zone II (P < 0.001). In this pilot study, PET was used for the first time for studying the adipose tissue perfusion in different zones in free flaps in a clinical setup, finding that the mean BF(PET) values did not differ between DIEP and TRAM flaps, and that zone II was sometimes not as well perfused as zone III supporting revisited zone division.     

Magnetic particle imaging: Introduction to imaging and hardware realization

Magnetic Particle Imaging (MPI) is a recently invented tomographic imaging method that quantitatively measures the spatial distribution of a tracer based on magnetic nanoparticles. The new modality promises a high sensitivity and high spatial as well as temporal resolution. There is a high potential of MPI to improve interventional and image-guided surgical procedures because, today, established medical imaging modalities typically excel in only one or two of these important imaging properties. MPI makes use of the non-linear magnetization characteristics of the magnetic nanoparticles. For this purpose, two magnetic fields are created and superimposed, a static selection field and an oscillatory drive field. If superparamagnetic iron-oxide nanoparticles (SPIOs) are subjected to the oscillatory magnetic field, the particles will react with a non-linear magnetization response, which can be measured with an appropriate pick-up coil arrangement. Due to the non-linearity of the particle magnetization, the received signal consists of the fundamental excitation frequency as well as of harmonics. After separation of the fundamental signal, the nanoparticle concentration can be reconstructed quantitatively based on the harmonics. The spatial coding is realized with the static selection field that produces a field-free point, which is moved through the field of view by the drive fields.This article focuses on the frequency-based image reconstruction approach and the corresponding imaging devices while alternative concepts like x-space MPI and field-free line imaging are described as well. The status quo in hardware realization is summarized in an overview of MPI scanners.     

Invasive, aggressive basal cell carcinoma: carcinoma basocellulare terebrans—ulcus terebrans

The clinical picture, treatment and course of invasive, aggressive basal cell terebrans carcinoma of the face, scalp and neck in eight patients is presented in detail. Based on the analysis of these patients, as well as our experience of a total of 93 patients with aggressive, invasive basal cell carcinoma, treated so far, the conclusion is reached that basal cell terebrans carcinoma develops mainly on recurrences, that is on residual tumors, after inadequate surgical and radiation therapy. It was observed that the most aggressive tumors are those, which develop in residual tumors after radiation therapy. Due to extraordinary infiltrational growth, especially into deep structures (muscles, bones, cartilages, dura, and brain), even with extensive, mutilating operations one can never be sure that the tumor is radically removed. That is why in such cases, after extensive, mutilating operations, radiation therapy is recommended, if possible.     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.