Shame, guilt, and communication in lung cancer patients and their partners.

Lung cancer patients report the highest distress levels of all cancer groups. In addition to poor prognosis, the self-blame and stigma associated with smoking might partially account for that distress and prevent patients from requesting help and communicating with their partners. The present study used innovative methods to investigate potential links of shame and guilt in lung cancer recovery with distress and marital adjustment. A specific emphasis was an examination of the impact of shame on partner communication. Lung cancer patients (n = 8) and their partners (n = 8) completed questionnaires and interviews that were videotaped. We report descriptive statistics and Spearman correlations between shame and guilt, relationship talk, marital satisfaction, distress, and smoking status. We coded the interviews for nonverbal expressions of shame. Greater self-reported shame was associated with decreased relationship-talk frequency and marital satisfaction, and with increased depression and smoking behaviour. Nonverbal shame behaviour also correlated with higher depression and increased smoking behaviour. Guilt results were more mixed. More recent smoking behaviour also correlated with higher depression. At a time when lung cancer patients often do not request help for distress, possibly because of shame, our preliminary study suggests that shame can also disrupt important partner relationships and might prevent patients from disclosing to physicians their need for psychosocial intervention and might increase their social isolation. Even if patients cannot verbally disclose their distress, nonverbal cues could potentially give clinicians an opportunity to intervene.

Effect of indomethacin on motor activity and spinal cord free fatty acid content after experimental spinal cord injury in rabbits.

STUDY DESIGN: Determination of functional and biochemical parameters as well as the effect of specific therapies on these parameters, in the experimental model of neurotrauma in rabbits. OBJECTIVE: To assess the effect of indomethacin (0.1-3.0 mg/kg for 9 days), a potent inhibitor of endogenous prostaglandin synthesis, on the motor activity and on the spinal cord tissue concentration of free palmitic, stearic, oleic, arachidonic and docosahexaenoic acids in an experimental model of a spinal cord injury in rabbits. SETTING: Faculty of Medicine, University of Rijeka, Croatia. METHODS: The animals were randomly divided into nine experimental groups, four sham and/or vehicle-treated and five indomethacin-treated (including one sham-operated and four injured groups). Laminectomy was followed by contusion of the spinal cord, using a modification of the technique of Albin. Motor activity was controlled daily during the course of the next nine postoperation days and scored using Tarlov's system. Spinal cord samples from the impact injury site were taken and frozen in liquid nitrogen. Total lipids were isolated and purified by a modification of the method of Folch. Free fatty acids (FFAs) were separated from the total lipid extract by preparative thin-layer chromatography, converted to the corresponding methyl esters and identified using gas chromatography, using nonadecanoic acid as the internal standard. RESULTS: The concentrations of all analysed free fatty acids were increased in the spinal cord after neurotrauma, in comparison to control tissues. Treatment of injured rabbits with indomethacin resulted in a significant decrease in spinal cord FFAs and exerted a positive effect on neurotrauma-induced motor impairment. CONCLUSION: These results indicate a mechanism whereby indomethacin protects rabbits from the sequellae of neuronal damage caused by trauma, and suggests that it may be beneficial in the therapy of neurotrauma. SPONSORSHIP: This work was supported by the Croatian Ministry of Science and Technology (project 062019).

Fluidity of the myelin sheath in the peripheral nerves of diabetic rats.

In the present study we examined the structural integrity of the myelin sheath in the peripheral nerves from short-term streptozotocin (STZ)-treated diabetic rats, using ESR spectroscopy as a tool in determining the dynamic state and the structure of the myelin lipid phase. Experiments were performed on spin-labeled sciatic and sural nerves from STZ-treated Hannover-Wistar rats and age-matched controls. The spectrum analysis employed a numerical simulation model with the set of fitting parameters that in the same time relate the ESR line shape and structure and dynamics of the probed environment. The simulation considered three spectral components weighted and summed in the composite spectrum. The comparative analysis of results showed the fraction of the spectral component II to be significantly increased in the spectra of diabetic rats, indicating the significant increase in overall fluidity of the myelin structure. The origin of fluidity changes was further investigated using an experimental model for demyelination (local injection of ethidium bromide in vivo), proteolytic action of trypsin in vitro, and osmotic myelin swelling in vitro. Analysis and comparison of the results suggested a conclusion in terms of changed biophysical properties of the myelin lipid phase in peripheral nerves in the pathology of diabetes.

Altered activities of rat brain metabolic enzymes in electroconvulsive shock-induced seizures.

PURPOSE: Electroconvulsive shock (ECS) induces generalized seizure activity and provides an excellent experimental model for studying the effects of global electrical stimulation on various biochemical parameters. The aim of this work was to investigate the influence of a single or repeated ECS-induced seizures on rat brain metabolism. METHODS: Experiments were carried out on female Hannover-Wistar rats divided into four groups: (a) the control group, which was intact; (b) the 1ECS group, which was killed 2 h after single ECS; (c) the 5ECS group with 24 h rest, which was killed 24 h after the fifth daily ECS; and (d) the 10ECS group with 48 h rest, which was given ECS every 48 h and killed 24 h after the tenth ECS. Activities of glutamate dehydrogenase (GLDH), aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK) in the frontal cortex, cerebellum, hippocampus, and pons/medulla regions were determined. RESULTS: Increased AST, ALP, LDH, and CK activities were detected in all examined regions of the 1ECS and 5ECS groups. ALT activity was increased in both these groups, except in the hippocampus of the 5ECS group, where increased GGT activity was detected. In the hippocampus of 1ECS group, GLDH activity was decreased. Increased hippocampal AST and cortical CK activities, together with increased LDH activities in the cortex, cerebellum, and pons/medulla, were found. CONCLUSIONS: ECS treatment induces region-specific changes in metabolic activity. Neither a 24-h nor a 48-h rest period between two ECSs was sufficient for complete brain recovery, although most of the observed increased enzyme activities present in 1ECS and 5ECS were not present in 10ECS.

Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol--induced seizures.

The aim of our study was to investigate amino acid and energy metabolism of pentylenetetrazol (PTZ)-kindled animals. Glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamyltransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined in the frontal cortex, cerebellum, hippocampus and pons-medulla regions of Hannover-Wistar rats. The rats were randomly divided into four experimental groups: (a) control; (b) rats which received a single PTZ injection in a subconvulsive dose of 40 mg/kg i.p.; (c) rats which received a single PTZ injection in a convulsive dose of 50 mg/kg i.p.; and (d) PTZ-kindled rats. Kindling increased ALP activity throughout the brain, elevated AST as well as LDH activity in the frontal cortex and hippocampus and decreased CK activity in the frontal cortex and cerebellum. Acute seizures of the same intensity did not induce these alterations. The observed effects therefore are obviously linked to the kindling phenomenon and not to seizure activity. Changes appeared mainly in the frontal cortex and hippocampus, i.e. brain areas believed to be directly involved in kindling.

Electroconvulsive shock in rats: changes in superoxide dismutase and glutathione peroxidase activity.

Seizures trigger a variety of biochemical processes including an influx of extracellular Ca(2+), activation of membrane phospholipases, liberation of free fatty acids, diacylglycerols, eicosanoids, lipid peroxides and free radicals. These lipid metabolites along with abnormal ion homeostasis may be involved in cell injury and cell death. The aim of this study was to determine brain antioxidant enzyme activities in rats with electroconvulsive shock (ECS)-induced seizures. ECS, single or repeated, induced a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in various brain regions. The most prominent changes of enzymatic activities were observed in rats that received five ECSs with 24-h recovery period between them. Decreased SOD activity was observed in the frontal cortex of all treated animals except those sacrificed 24 h after single ECS, in the cerebellum of the animals that received repeated ECSs, in the hippocampus of animals that were decapitated 2 h after a single ECS and in the pons-medulla region of rats that received five daily ECSs. Decreased GPX activity was found in all examined brain regions of the rats that received five ECSs, the cortex and hippocampus of rats that were decapitated 2 h after single ECS and the cortex of those that received 10 ECSs with 48 h between them. The results show that neither 24-h nor 48-h recovery period was sufficient for the normalisation of antioxidative enzyme activities after repeated ECS treatment.

Lithium plus pilocarpine induced status epilepticus--biochemical changes.

The aim of the study was to investigate the changes in biochemical mechanisms facilitating cellular damages in the lithium plus pilocarpine treatment and the resulting status epilepticus. The whole brain free fatty acid (FFA) level as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamoyl transferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase in the frontal cortex, cerebellum, hippocampus and pons-medulla region of Hannover-Wistar rats were determined. The control group was intact with no previous experimental history. LiCl (125 mg/kg i.p.) was injected 20 h prior to pilocarpine (30 mg/kg i.p.) and the treated rats were sacrificed 1 or 2 1/2 h after pilocarpine administration. The results show that lithium plus pilocarpine administration and the resulting status epilepticus produced the significant increase of the brain FFA content. Decreased GPX activities were detected in the frontal cortex, cerebellum and hippocampus of the treated rats without the accompanying decrease of SOD activity. Increased AST and LDH activities were observed in the frontal cortex, increased soluble ALP activities in the frontal cortex and pons-medulla region whereas the increased activity of membrane bound ALP was detected in the hippocampus of the rats with status epilepticus. Activities of the other analysed enzymes did not change in the examined brain regions. The presented data indicate clear regional differences of biochemical changes caused by lithium plus pilocarpine treatment and the resulting status epilepticus, frontal cortex being the most affected site.

The influence of nimodipine, nicardipine and amlodipine on the brain free fatty acid level in rats with penicillin-induced seizures.

1. The aim of this study was to investigate the effects of the calcium channel blockers, nimodipine, nicardipine and amlodipine, on the brain free fatty acid (FFA) level in rats with chemically-induced seizures. 2. The study was carried out on Hannover-Wistar rats. Animals were anesthetized and placed in a stereotaxic apparatus. Each of them received an injection of penicillin (5000 IU/5 microliters) into the left lateral ventricle (i.c.v.). Various doses (1, 3, 10 or 30 mg/kg) of nimodipine, nicardipine or amlodipine had been injected i.p. 30 min before the penicillin application. The rats were decapitated 5 min after the occurrence of epileptic seizures. FFAs were quantified by gas chromatography using the internal standard method. 3. The results demonstrate that i.c.v. injection of penicillin was associated with significant increase in the brain FFA concentration. Tested doses of nicardipine and amlodipine did not influence the increase of the brain free palmitic, stearic, oleic and arachidonic acid level while nimodipine prevented the accumulation of free palmitic, oleic and arachidonic acid in rats with penicillin-induced seizures. Statistically insignificant decrease of steric acid was observed in animals pretreated with nimodipine. 4. It maybe assumed that the brain FFA accumulation caused by i.c.v. penicillin administration is not predominantly associated with a disturbance in calcium homeostasis via L-type voltage-sensitive calcium channels, but by some other membrane and/or intracellular mechanisms.

Education in clinical pharmacology at the Rijeka School of Medicine, Croatia.

OBJECTIVE: Irrational drug prescribing is a global problem that exists both in developed and developing countries. Education is the key to improved effectiveness and safety in drug therapy. Development of clinical pharmacology (CP) as an independent discipline at the Rijeka School of Medicine has been slow and unsatisfactory. It was taken only as a part of some postgraduate courses. In the 1995/1996 academic year clinical pharmacology was offered for the first time to sixth year medical students as a non-mandatory subject. The purpose of this study was to emphasize the importance of education in clinical pharmacology at the Rijeka School of Medicine. METHODS: This survey was an uncontrolled study based on responses to questionnaires and a test consisting of written patient problems given to sixth year medical students and to general practitioners who were following a course in clinical pharmacology. RESULTS: The results of the questionnaire showed that both undergraduate and postgraduate students consider that they are not being adequately trained to prescribe drugs rationally and that they believe that clinical pharmacology should become a mandatory subject in the undergraduate medical curriculum. The results of the written patient problem test support this. Both groups of students demonstrated greater skills in solving the diagnostic part than the therapeutic part of the test. A great improvement in the students' ability to solve the therapeutic part was observed after they had completed the CP course. CONCLUSION: The results of this survey underline the necessity of education in clinical pharmacology.

The influence of nicardipine and ifenprodil on the brain free arachidonic acid level and behavior in hypoxia-exposed rats.

1. The effects of the calcium channel blockers, nicardipine and ifenprodil, on the brain free arachidonic acid level and learning ability in rats exposed to hypoxia were examined. 2. Adult rats were injected with 0.003; 0.01; 0.03; 0.1; 0.3 or 1.0 mg/kg of tested drugs i.p. Thirty min later the learning ability was tested in a passive avoidance task according to the step-through procedure. Immediately after the training trial, the animals were subjected to a period of oxygen deprivation hypoxia until the loss of the righting reflex. The retention trial was carried out 24 hr later. 3. The other groups of animals were pretreated with mentioned substances before hypoxia-exposure. Fifteen min after the loss of the righting reflex they were decapitated and brains were frozen in liquid nitrogen. The brain free arachidonic acid level was quantified by gas chromatography. 4. Both nicardipine and ifenprodil were effective in preventing a memory decline in hypoxia-exposed rats but did not prevent the accumulation of the brain free arachidonic acid in hypoxia-exposed rats. 5. The protective effects of both substances in behavioral studies during acute brain damage caused by hypoxia could not be explained by the prevention of the increase of the brain free arachidonic acid, but by some other mechanism.

The influence of nimodipine and MK-801 on the brain free arachidonic acid level and the learning ability in hypoxia-exposed rats.

1. The influence of voltage dependent calcium channel blocker (VDCC), nimodipine and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 on the brain free arachidonic acid (FAA) level and on the learning ability in hypoxia-exposed rats was examined. 2. Some animals were decapitated after cerebral hypoxia had been obtained and the brain FAA level was determined by gas chromatography. The other animals were trained in a passive avoidance procedure and were exposed to hypoxic conditions immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. 3. Various doses of nimodipine (0.03; 0.1; 0.3 and 1.0 mg/kg) and MK-801 (0.03; 0.1 and 0.3 mg/kg) had been injected 30 minutes before biochemical or behavioral procedures started. 4. It was found that hypoxia strongly increased the brain FAA level and impaired the retention of the passive avoidance response. 5. Pretreatment with 0.3 mg/kg and 1.0 mg/kg of nimodipine prevented the brain FAA accumulation. It has also been shown that all tested doses of nimodipine significantly improved the retention deficit in the animals exposed to hypoxia. 6. Neither the one of tested doses of MK-801 influenced significantly the increase of the brain FAA level and/or passive avoidance behavior in hypoxic animals. 7. These results confirm the hypothesis that the brain FAA accumulation and cognitive impairment, caused by hypoxia, are maybe associated with disturbances in calcium homeostasis and that nimodipine may be useful in ameliorating the hypoxia-induced brain tissue damage. Blocade of NMDA receptor-channel complex by MK-801 was not sufficient to prevent hypoxia-induced neuronal damage.

Effects of nimodipine, felodipine and amlodipine on electroconvulsive shock-induced amnesia in the rat.

The effects of various doses (0.03, 0.1, 0.3 or 1.0 mg/kg) of the Ca2+ channel blockers nimodipine, felodipine and amlodipine on the learning ability of rats exposed to electroconvulsive shock were examined. The animals were trained in a passive avoidance procedure. The drugs tested were injected 30 min before the learning trial started. The electroconvulsive shock was given immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 h later. It was found that electroconvulsive shock strongly impaired the retention of the passive avoidance response. Nimodipine, felodipine and amlodipine did not influence the passive avoidance behavior in the sham electroconvulsive shock group, but significantly improved the retention deficits in the animals exposed to electroconvulsive shock. These findings support the hypothesis that perturbations in Ca2+ homeostasis can contribute to the memory deficits associated with electroconvulsive shock. The antiamnestic effects of the substances tested make them interesting candidates for clinical trials in patients with cognitive impairment caused by electroconvulsive shock therapy.

Effects of nicardipine, felodipine and nifedipine on passive avoidance behavior of intact and hypoxia-exposed rats.

The effects of various doses (0.03, 0.1, 0.3 or 1 mg/kg) of the calcium channel blockers nicardipine, felodipine and nifedipine on the learning ability in intact rats and on hypoxia-induced retention deficits were examined. All animals were trained in a passive avoidance procedure. The drugs tested had been injected 30 minutes before the learning trial started. Some animals were exposed to a hypoxic condition immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. It was found that hypoxia strongly impaired the retention of the passive avoidance response. Nicardipine, felodipine and nifedipine did not influence the passive avoidance behavior in the intact animals, but significantly improved the retention deficits in the animals exposed to hypoxia. The effects of the substances tested were dose-dependent. These findings support the hypothesis that perturbations in calcium homeostasis can contribute to the memory deficits associated with hypoxic conditions.

Clinical pharmacology in Eastern European countries.

The current status of clinical pharmacology (CP) in the countries of the former Eastern block is presented. The difficulties in obtaining an accurate comparative view are pointed out. CP is unevenly developed in Eastern European countries and the number of hours devoted to basic/clinical pharmacology differs considerably 100/nil to 240/50. The same is true for the orientation of clinical pharmacology, where present. It is mainly basic in only a few countries (Rumania, Turkey, some parts of the former Yugoslavia) and mainly clinical in Czecho-Slovakia, Croatia, Hungary, Poland, Greece. The number of CP units and CP specialists varies greatly as well (from none to more than 10 per country). The awareness that CP, in many countries is still young and the branch of (clinical) medicine is of great importance, not only for rational pharmacotherapy but also for other services as well, education and research is growing. In spite of the fact that the present status of CP in Eastern European countries is generally unsatisfactory, there are realistic chances that in the (near?) future, CP will develop to match the activities now present in the more developed countries.

Influence of various cholinergic and anticholinergic drugs on rectal temperature in rats.

The influence of various cholinergic drugs on rectal temperature of rats under controlled laboratory conditions was examined. Animals were anaesthetized by intraperitoneal injection of thiopental. Three hours later acetylcholine, methacholine, arecoline, nicotine, neostigmine, atropine, methylatropine, mecamylamine or hemicholinium were injected intrahypothalamically (i.h.), intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.). Rectal temperature was measured at 15 min-intervals for 1 hr after the substances were injected. Our results indicate that the cholinergic mechanisms play an important role in thermoregulatory processes in rats. Cholinergic activation decreases rectal temperature, due to an increased activity of central, and not of peripheral cholinergic neurotransmission. The hypothermic effect of cholinomimetics is mediated through an activation of muscarinic cholinergic receptors.

The influence of piracetam on the motor activity of rabbits with contusioned spinal cord.

Rabbits were made paraplegic by spinal cord contusion. There was a good correlation between motor function and microscopic findings. The spinal lesion significantly increased creatine kinase (CKBB) isoenzyme activity in cord tissue. Significant protection from paralysis was conveyed by piracetam (a psychoactive drug with neuroprotective activity) (2 g.kg-1 i.v.) administered once per day during 9 posttraumatic days. Piracetam significantly diminished increased activity of CKBB in the severed spinal cord. The sooner the piracetam was injected after the lesion the better protective effect was seen. No side effects of piracetam were seen.

Effect of piracetam on motor activity of spinal cord injured rabbits.

Experimental, lumbal spinal cord compact injury provoked by a strike of 71 p.cm caused a spontaneously irreversible paraplegy in rabbits. Motor activity of injured rabbits was controlled during nine posttraumatic days. Piracetam significantly reduced motor dysfunction of the hind legs. Piracetam (2 g.kg-1) was given i.v., once per day during nine posttraumatic days. The beneficial effect of piracetam was more pronounced when the delay between trauma and the onset of drug administration was shorter. When this delay amounted to 360 minutes, piracetam did not influence significantly motor activity of contusioned animals. No side effects of piracetam were observed.

[The importance of histaminergic H1 and H2 receptors for the contractile effect of histamine on human umbilical veins]. / Znacenje histaminskih H1 i H2 receptora za kontraktilno djelovanje histamina na humanu umbilikalnu venu.

Influence of histamine and histaminergic H1 blockers (antazoline, promethazine) and H2 blockers (cimetidine, ranitidine) on isometric contraction of helically cut strips of human umbilical vein was examined. Histamine produced dose-related contraction of the vein strip, while histaminergic H1 and H2 blockers did not changed the tonus of the vein. The contractile activity of histamine was not influenced by cimetidine or ranitidine, while antazoline and promethazine antagonized mentioned activity of histamine completely. We suppose that histamine exerts contractile effect of human umbilical vein by acting on H1 receptors while H2 receptors are not involved in the mentioned activity of histamine.