Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - in vivo experiments on the dunning rat tumor model

OBJECTIVE: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) in an in vivo tumor model. METHODS: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques. Thereafter, PDT using 150 mg 5-ALA/kg b.w. i.v. was performed by homogenous irradiation of the photosensitized tumor (diode laser lambda = 633 nm). The tumors were resected 2 days post-PDT and the extent of the necrosis was determined histopathologically. RESULTS: The kinetics of PPIX fluorescence revealed a maximum intensity in the tumor tissue within 3 and 4.5 h post-application of 5-ALA. At this time, specific PPIX fluorescence could be localized selectively in the tumor cells. The PDT-induced necrosis (n = 18) was determined to be 94 +/- 12% (range 60-100%), while the necrosis of the controls (n = 12) differs significantly (p < 0.01), being less than 10%. CONCLUSION: These first in vivo results demonstrate the effective potential of 5-ALA-mediated PDT on PCA in an animal model.     

Fatal hypertensive encephalopathy in a child with association of multicystic kidney and renal artery stenosis

At the age of 5 years, a boy with known multicystic dysplastic kidney disease showed signs of arterial hypertension with progress to fatal hypertensive encephalopathy. Arterial hypertension was refractory to antihypertensive therapy and the child lost consciousness. Computed tomography of the brain revealed multiple cerebral infarctions. Doppler ultrasound showed an elevation of blood flow in the main artery of the functioning kidney consistent with stenosis as a cause of hypertension. CONCLUSION: Arterial hypertension is a known complication of kidney disease. Multicystic dysplastic kidney and renal artery stenosis is a potentially fatal association. Careful evaluation and monitoring, with special emphasis on blood pressure, should be performed in children with multicystic dysplastic kidney disease.     

Central osmotic regulation of sympathetic nerve activity

AIM: In this review, we will focus on the central neural mechanisms that couple osmotic perturbations to changes in sympathetic nerve discharge, and the possible impact these actions have in cardiovascular diseases such as arterial hypertension and congestive heart failure. RESULTS: Changes in extracellular fluid osmolality lead to specific regulatory responses in defence of body fluid and cardiovascular homeostasis. Systemic hyperosmolality is well known to stimulate thirst and the release of antidiuretic hormone. These responses are largely due to osmosensing neurones in the forebrain lamina terminalis and hypothalamus and are critical elements in a control system that operates to restore body fluid osmolality. An equally important, but less characterized, target of central osmoregulatory processes is the sympathetic nervous system. CONCLUSION: Understanding the neurobiology of sympathetic responses to changes in osmolality has important implications for body fluid and cardiovascular physiology. By stabilizing osmolality, vascular volume is preserved and thereby relatively normal levels of cardiac output and arterial pressure are maintained.     

Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels

Maurotoxin, a 34-amino acid toxin from Scorpio maurus scorpion venom, was examined for its ability to inhibit cloned human SK (SK1, SK2, and SK3), IK1, and Slo1 calcium-activated potassium (K(Ca)) channels. Maurotoxin was found to produce a potent inhibition of Ca(2+)-activated (86)Rb efflux (IC(50), 1.4 nM) and inwardly rectifying potassium currents (IC(50), 1 nM) in CHO cells stably expressing IK1. In contrast, maurotoxin produced no inhibition of SK1, SK2, and SK3 small-conductance or Slo1 large-conductance K(Ca) channels at up to 1 microM in physiologically relevant ionic strength buffers. Maurotoxin did inhibit (86)Rb efflux (IC(50), 45 nM) through, and (125)I-apamin binding (K(i), 10 nM) to SK channels in low ionic strength buffers (i.e., 18 mM sodium, 250 mM sucrose), which is consistent with previous reports of inhibition of apamin binding to brain synaptosomes. Under similar low ionic strength conditions, the potency for maurotoxin inhibition of IK1 increased by approximately 100-fold (IC(50), 14 pM). In agreement with its ability to inhibit recombinant IK1 potassium channels, maurotoxin was found to potently inhibit the Gardos channel in human red blood cells and to inhibit the K(Ca) in activated human T lymphocytes without affecting the voltage-gated potassium current encoded by Kv1.3. Maurotoxin also did not inhibit Kv1.1 potassium channels but potently blocked Kv1.2 (IC(50), 0.1 nM). Mutation analysis indicates that similar amino acid residues contribute to the blocking activity of both IK1 and Kv1.2. The results from this study show that maurotoxin is a potent inhibitor of the IK1 subclass of K(Ca) potassium channels and may serve as a useful tool for further defining the physiological role of this channel subtype.     

Toward integrating a common nursing data set in home care to facilitate monitoring outcomes across settings

The purpose of our research is to identify a realistic subset of North American Nursing Diagnosis Association (NANDA), Nursing Outcome Classification (NOC), and Nursing Interventions Classification (NIC) terms specific to the home care (HC) setting. A subset of 89 NOC outcomes were identified for study in HC through a baseline survey. Three research assistants then observed the care of 258 patients to whom the 89 NOC outcomes applied and recorded the associated NANDA and NIC terms. Follow-up surveys and focus groups were conducted with the nurses and research assistants. There were 81 different NANDA and 226 NIC labels used to describe study patients' care. Only 36 of the 89 NOC labels studied were deemed clinically useful for HC. We found that expert opinion about terminology usage before actual experience under practice conditions is unreliable.     

Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.     

Sequestrations of the lung

Sequestration of the lung is a well-recognized entity usually subclassified into one of two groups based on its location: intralobar sequestration (ILS), within the normal pleural investment, and extralobar sequestration (ELS), outside the normal pleural investment. ELS is clearly congenital in origin; it is seen most frequently in the neonatal period, is associated with other anomalies, and is supplied by systemic and/or pulmonary arteries. ILS, on the other hand, in the majority of cases, probably results from repeated episodes of chronic pneumonia producing, through the process of granulation tissue formation, parasitization of normally occurring pulmonary ligament arteries resulting in a systemic artery supply to the infected area of lung. Its location (almost exclusively in the lower lobes) is dependent on the availability of systemic arteries situated only in pulmonary ligaments between the lower lobes and the mediastinum. Further support for the acquired nature of this lesion is its almost complete absence in neonates and infants, the infrequency of associated anomalies, and the consistent features of chronic inflammation and fibrosis within resected specimens.