Editorial

Ohne Zusammenfassung     

Saethre-Chotzen syndrome (ACS III) in four generations

The acrocephalosyndactylies (ACS) are a group of inherited disorders characterized by premature fusion of cranial sutures in association with abnormalities of the hands and feet. Based on their clinical features, different types of ACS have been described. We here report on a family with 9 individuals affected with ACS III (Saethre-Chotzen syndrome), 5 of them severely. Clinical features of the patients are presented with regard to differential diagnostic delineations.     

Quantitative and comparative study of haematoporphyrin-derived photosensitizers on a murine tumour model

Eight commercially available HPD-photosensitizers intended for photodynamic therapy were tested in a murine tumour model with regard to their therapeutic efficacy. The regrowth delay of the fibrosarcoma SSK-2 on the mouse C3H, Neuherberg-line, was determined 3, 24, 48 and 72 h after injection of the drugs (dose: 9 mg kg^–1 body weight). The corresponding pharmacodynamics, as measured by regrowth delay, were approximated by an exponential function and the characterizing coefficients derived. These coefficients served to quantify the photodynamic properties of the drugs.The pharmacodynamics of five substances were compared with those obtained fluorometrically. The latter showed shorter decay constants than the therapy-correlated substances which indicates different metabolic behaviour of the therapeutic and diagnostically useful fluorescent components of haematoporphyrin-derived photosensitizers.     

How large must an epileptic focus be to cause an electrographic status epilepticus--a case report.

Based on experimental data from animal studies different theories regarding the size of an epileptic focus have been postulated which range from single pacemaker cells to extended neuronal networks. We report a case which gives further information about the size of a human epileptic focus which can trigger manifest epileptic seizures. We report a 22-year-old man with medically refractory temporal lobe epilepsy. This patient suffered from brief complex partial seizures and frequent epigastric auras. To differentiate a mesiotemporal from a temporolateral seizure origin the patient was implanted with a 10 contact depth electrode from a posterior approach into the right hippocampus, and additional temporobasal/temporolateral subdural strip electrodes. Depth recordings revealed an electrographic status with continuous rhythmic sharp wave activity (1 Hz), the field of which was confined to a diameter of less than 1 cm in the anterior hippocampus, whereas temporobasal subdural strip electrodes did not display this activity. Periodically, spread of this activity occurred to the amygdala, to the posterior part of the hippocampus, and less often to the temporobasal cortex. Most seizure patterns remained subclinical, few of them became symptomatic as partial seizures. This case demonstrates that a hippocampal epileptic focus causing electrographic focal status epilepticus may be limited to a volume of less than 1 cm in diameter. This observation is discussed with regard to implantation strategies and to possible superselective resective or modulatory approaches in the treatment of such limited epileptogenic areas.     

Self‐Neglect: A Proposed New NANDA Diagnosis

PURPOSE. To propose a new NANDA diagnosis, self‐neglect. DATA SOURCES. Research studies and literature published from a variety of disciplines including nursing as well as primary research. DATA SYNTHESES. This diagnosis can be used to describe a constellation of self‐care problems of varying severity and impact on the health and well‐being of people who self‐neglect. Included are two subtypes of self‐neglect based on the degree of intentionality. Clarification of self‐neglect is long overdue because self‐neglect presents conceptual, identification, and intervention problems for nurses, healthcare workers, and for medicolegal systems across settings and in many countries. CONCLUSION. The proposed diagnosis, self‐neglect, fills a gap in current standardized terminology. This diagnosis will contribute significantly to nurses leading the way in the explication of an interdisciplinary and international health concern. PRACTICE AND POLICY IMPLICATIONS. Developing self‐neglect as a recognized nursing label is vital to clinicians and policy makers within and across countries. Appreciating less serious/non‐life‐threatening presentations will give nurses a care perspective to improve the health and well‐being of those in earlier stages of self‐neglect. Definitions for this phenomenon will contribute to care planning and interventions, leading to consistency in practice and research.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Time-dependent morphological alterations of cold-stored small bowel in Euro-Collins and Ringer's lactate solutions

Small bowel is one of the organs that can in principle be transplanted. Optimum preservation of the organ is essential for the success of transplantation. The aim of the present study is the investigation of time-related morphological changes of rat small bowel during preservation in hypothermic Euro-Collins (EC) and Ringer's lactate (RL) solution using light microscopy and transmission electron microscopy to evaluate the integrity of intercellular complexes of mucosal epithelium, one of the tissues of the intestine that is most susceptible to ischemia. Small bowels were perfused with either EC, RL solution or physiological saline solution and were placed in the different preservation solutions at 4 degrees C for 0, 3, 6 and 12 h. The results of our study suggest that both preservation solutions are suitable for short-term preservation of the small bowel although RL solution is more effective than EC solution. However, we conclude that further improvement of preservation solutions and/or techniques are needed to perform long-term preservation.     

Regulatory effects of biophysical strain on rat TMJ discs

Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair.