Gender difference in cytokine secretion on immune stimulation with LPS and LTA.

Immune defense capacity differs between men and women. Whereas men are more prone to infection and sepsis, women more commonly develop autoimmune diseases. We investigated the difference in cytokine secretion between males and females in response to different immune stimuli. Whole blood from 154 healthy volunteers (age 24 +/- 5.2; 82 females, 72 males) was collected within 2 h on 2 consecutive days. Blood from males produced significantly more tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and IL-8 than blood from females in response to a high concentration of either lipopolysaccharide (LPS) or lipoteichoic acid (LTA), whereas IL-10 and interferon-gamma (IFN-gamma) secretion did not differ. Normalization of cytokine measurement to individual monocyte counts cancelled these differences for all parameters except TNF-alpha. Stimulation with a lower concentration of LPS (100 pg/mL) produced even stronger differences in cytokine release, which were not cancelled by normalization to the producing cells. The coefficients of variation (CV) of the LPS-induced and LTA-induced cytokine responses were higher in blood from women than men for all parameters and stimuli measured. Thus, the stronger innate immune response of males in comparison to females appears to stem not only from a difference in monocyte counts but also from the steepness of the response curve.     

Detection of disseminated tumor cells in the lymph nodes of colorectal cancer patients using a real-time polymerase chain reaction assay

Introduction Postoperative treatment for colorectal cancer depends on tumor stage as defined by the International Union Against Cancer (UICC). Adjuvant chemotherapy is not recommended in patients without lymph node involvement (UICC stages I and II). As many as 20–30% of these patients, however, will develop recurrence. Aims and objectives We conducted this study to determine the presence of disseminated tumor cells in the lymph nodes by quantitative real-time polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to provide supplementary information compared to histopathological findings. Materials and methods Using a standard QRT-PCR assay, we examined primary tumors and 391 lymph nodes from 31 patients with completely resected colorectal cancer. Results Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR. Discussion An examination of the lymph nodes from the 29 patients with CK20-positive primary tumors revealed that 35 (92.1% sensitivity) of the 38 histopathologically positive lymph nodes and 54 (16.7%) of the 324 histopathologically negative lymph nodes were positive by molecular analysis. CK20 expression was detected in 10 (100%) of 10 patients with a histopathologically positive lymph node status (pN1). In 9 (47.4%) of 19 patients with negative histopathological results (pN0), we detected a CK20 mRNA signal in at least one lymph node. Whereas eight patients with histopathologically negative lymph nodes could be upstaged on the basis of the molecular findings, no patient would be downstaged. Conclusion Our results suggest that QRT-PCR for CK20 is a useful tool for the quantitative detection of micrometastases in the regional lymph nodes. We introduce a standardized procedure that integrates a molecular diagnostic technique in the clinical staging.     

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.