Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As₂O₃ toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As₂O₃. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD₅₀ of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As₂O₃ poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As₂O₃ (containing a tracer dose of⁷⁴As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated.     

Effects of FR173657, a non-peptide B2 antagonist,on kinin-induced hypotension,visceral and peripheral oedema formation and bronchoconstriction

1. Kinins are believed to play a key role in many inflammatory conditions. Therefore, bradykinin antagonists are being developed for potential therapeutic applications. In the present investigation we describe the pharmacology, in vivo, of (E)-3-(6- acetamido- 3-pyridyl)- N-[N- [2,4- dichloro- 3-[(2- methyl-8- quinolinyl)oxymethyl]phenyl]- N-methylaminocarbonylmethyl]acrylamide ({"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657), a novel, non-peptide bradykinin antagonist.
2. The hypotensive effects of i.v. injections of bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were significantly inhibited by 100 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 s.c., and completely abolished by 300 nmol kg⁻¹. The full inhibitory effect developed within 60 min and remained unchanged for at least 4 h. However, the effect was reversible, since 24 h after an injection of 300 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 no inhibitory effect could be observed.
3. The plasma protein extravasation into the pancreas and duodenum induced by an i.v. infusion of bradykinin (11 nmol kg⁻¹ within 20 min) in captopril-treated anaesthetized rats was completely abolished by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 at doses of 30 nmol kg⁻¹ s.c. and above, given 60 min before bradykinin. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 3 nmol kg⁻¹ was ineffective, while a dose of 10 nmol kg⁻¹ produced an intermediate effect.
4. The paw oedema induced by the subplantar injection of bradykinin (30 nmol) in anaesthetized rats was inhibited slightly by s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 0.3 μmol kg⁻¹, whereas 1 and 3 μmol kg⁻¹ produced significant inhibition of the bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could not be increased even when the dose of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 was increased to 30 μmol kg⁻¹. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine.
5. Bradykinin (20 nmol kg⁻¹, i.v.) caused increases in pulmonary inflation pressure by 300–600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to 58±9% of the initial value 60 min after the s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 1 μmol kg⁻¹, whereas only 9±7% remained after 10 μmol kg⁻¹. The bronchoconstrictor actions of histamine remained unaffected by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657.
6. In summary, {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 is a highly potent and selective bradykinin antagonist. The inhibitory action in vivo lasts for longer than 4 h but is fully reversible. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657, or similar compounds, will be a useful tool for the pharmacological investigation of pathophysiological states and may possess a therapeutic potential in diseases involving the endogenous release of kinins.

     

Hirntumor und Kopfschmerz

Methods

The possible association of brain tumour with headache was investigated in 100 patients seen for brain surgery. Preoperatively, 43 patients suffered from headache. These patients were thoroughly questioned about the nature of their pain. Investigation included the McGill Pain Questionnaire.

Results

In only 11 of the patients was headache the primary symptom of a brain tumour. Pain intensity was found to be lower in patients with brain tumour then in those with extracranial tumours or headache of other origins. Female subjects, patients under 50 years of age and those with elevated intracranial pressure experienced more intensive pain. Diurnal variation in pain intensity was observed in 60% of patients with headache. There was no evidence, however, of an association with elevated intracranial pressure.

Conclusions

Our investigations yielded new information concerning the epidemology of headache accompanying brain tumours. Headache is not an early cardinal symptom of brain tumours, as was generally believed earlier. With the help of the McGill Pain Questionnaire a fine quantitative and qualitative characterization of headache of different origins could be made. The connection between tumour localization and pain lateralization, as well as the possible mechanisms of intracranial pain projection was extensively analysed. The interpretations of the results are at best hypotheses and they do not help determine why more than half of the patients with brain tumour did not experience headache.     

How to improve histopathological results in the biopsy diagnosis of gut dysganglionosis

In a methodological survey, the technical prerequisites for optimal histopathological diagnosis of gut dysganglionosis are presented. To make a proper diagnosis, the pediatric surgeon or gastroenterologist and the pathologist must consider certain preconditions. The most important steps for the optimal biopsy diagnosis of an aganglionosis, an ultrashort Hirschsprung segment, a intestinal neuronal dysganglionosis (IND), a ganglioneuromatosis, a hypogenesis, or immaturity of the vegetative gut innervation are: (1) taking 3–4 biopsies the size of a peppercorn (3–5 mm³) with submucosa; (2) the best instruments for taking rectal mucosal biopsies are forceps and scissors or a conventional large biopsy forceps; and (3) biopsies may be taken 1 cm, 3–4 cm, 6–9 cm, and 9–12 cm (or from a preternatural anus) above the pectinate line. A biopsy containing mucosa, muscularis mucosae, and submucosa guarantees a satisfying histopathological diagnosis. The native biopsies can be transported on water-ice if the distance to the pathologist takes no longer than 4–6 h. For long distances, biopsies have to be frozen on dry ice (CO₂ –80 °C) and transported in a sufficient amount of dry ice (adapted to the time of transportation). For biopsy processing, the following points are important: a total of 122 to 160 15-m-thick native cryostat serial sections have to be cut per biopsy and distributed on four microscope slides. Forty sections are used for lactic dehydrogenase reactions, 32 for succinic dehydrogenase reactions, and the rest for an acetylcholinesterase (AChE) reaction. An AChE reaction alone is sufficient for the diagnosis of Hirschsprung's disease (HD), but never for IND or other developmental malformations of the submucous and myenteric plexuses. Enzymehistotopochemical reactions allow the assessment of functional parameters. These reactions, in contrast to immunohistochemical staining, offer information about the functional activity of special gut structures, e. g., increased AChE activity in nerve fibers of the rectal wall in HD or a lack of dehydrogenase activity in immature ganglia.     

Oxidative reactions in the tear fluid of patients suffering from dry eyes

Purpose: To evaluate whether products of oxidative and inflammatory reactions are detectable in the tear fluid of patients suffering from dry eyes. Methods: The tear fluid of 217 patients (397 eyes) was sampled. Criteria for grouping of the patients were (1) basic secretion test (sicca l: BST = 0–5 mm, n = 78 eyes; sicca 2: BST = 6–10 mm, n = 109 eyes) and (2) subjective symptoms (normal BST, burning, foreign body sensations, tearing, dryness of the eyes: n = 78 eyes). One group of healthy patients (normal BST, n = 132 eyes) served as controls. Lipid peroxide levels and myeloperoxidase activity, as parameters for oxidative tissue damage and inflammatory activity, were determined in the tear fluid. Those patients whose consent could be obtained were subjected to the rose bengal test (sicca 1: 56 eyes; sicca 2: 97 eyes; subjective symptoms: 44 eyes; controls: 49 eyes). The correlation between BST and rose bengal test results was calculated. Results: Lipid peroxides were significantly (P < 0.05) higher in the groups sicca 1 and subjective symptoms than in healthy controls, as was the inflammatory activity in groups sicca 1, sicca 2 and subjective symptoms. Additionally, the inflammatory activity in the group sicca 1 was significantly (P < 0.05) higher than in the groups sicca 2 and subjective symptoms. No evidence of a significant correlation between BST and rose bengal test results was observed. Conclusions: Both oxidative tissue damage and polymorphonuclear leukocytes indicating an oxidative potential occur in the tear film of patients suffering from dry eyes. These reactions lead to severe damage of the involved tissue. Free radicals and inflammation may be involved in the pathogenesis or in the self-propagation of the disease.     

The combined effect of psychotherapy and fluoxetine on obesity]

Obesity as psychosomatic disease is a mass phenomenon. The number of obese males (BMI > 30) became doubled in the last ten years. In the etiology of obesity play an important role the reactive obesity. In the background of "yo-yo syndrome" often could be found depression, or other psychotic disorder. The low self-esteem, body dissatisfaction, tension, anxiety disorders is well-known in a slimming diet. Obese subjects (n = 29) who were admitted on their request with a view to losing weight were examined (Hamilton Depressive Scala, Hamilton Anxietas Scala, Eating Attitude Test) Physical Conditioning and internal Medicine Department of National Sports Medicine Institute, Budapest. Among obesities with mild and severe depression as treatment of somatic complications was used fluoxetine, in severe cases and depression with severe anxiety was associated with supportive or cognitive-behavioral treatment. The prevalence of binge eating disorders were at 57% and bulimia nervosa was at 3% in using population (n = 29). Decreasing of anxiety and grade of depression significantly correlated with body mass index (p < 0.023, F = 1.997, p < 0.034, F = 3.131). The treatment of fluoxetine significantly correlated with body mass index (T1: p < 0.023, T2: p < 0.03, T3: p < 0.004). The patients indicated their well being as fluoxetine reduced eating, satiety and lower binges.     

A taxonomy of requests by patients (TORP): a new system for understanding clinical negotiation in office practice

BACKGROUND: The goal of our investigation was to facilitate research on clinical negotiation between patients and physicians by developing a reliable and valid classification system for patients' requests in office practice. METHODS: We developed the Taxonomy of Requests by Patients (TORP) using input from researchers, clinicians, and patient focus groups. To assess the system's reliability and validity, we applied TORP to audiotaped encounters between 139 patients and 6 northern California internists. Reliability was assessed with the kappa statistic as a measure of interrater agreement. Face validity was assessed through expert and patient judgment of the coding system. Content validity was examined by monitoring the incidence of unclassifiable requests. Construct validity was evaluated by examining the relationship between patient requests and patient health status; patient request fulfillment and patient satisfaction; and patient requests and physician perceptions of the visit. RESULTS: The 139 patients made 772 requests (619 requests for information and 153 requests for physician action). Average interrater agreement across a sample of 40 cases was 94% (kappa = 0.93; P <.001). Patients with better health status made fewer requests (r = -0.17; P = .048). Having more chronic diseases was associated with more requests for physician action (r = 0.32; P = .0002). Patients with more unfulfilled requests had lower visit satisfaction (r = -0.32; P <.001). More patient requests was also associated with physician reports of longer visit times (P = .016) and increased visit demands (P = .006). CONCLUSIONS: Our study provides evidence that TORP is a reliable and valid system for capturing and categorizing patients' requests in adult primary care. Further research is needed to confirm the system's validity, expand its applicability, and explore its usefulness as a tool for studying clinical negotiation.     

Results of flexor-to-extensor and extensor brevis tendon transfer for correction of the crossover second toe deformity

Between 1990 and 1995, 38 patients (42 feet) underwent repair for crossover toe deformity, 31 (35 feet) of whom returned for final examination at an average of 51.6 months (range, 24-81 months). Causes included trauma, iatrogenic, and unknown. Presenting complaints included dorsal pain with either metatarsalgia or joint pain, isolated metatarsophalangeal (MP) joint pain, metatarsalgia, painful plantar callus, metatarsalgia and joint pain, and painful dorsal callus. All patients were treated with one of two operative techniques, either the flexor-to-extensor tendon transfer or the extensor brevis tendon transfer. Choice of procedure depended on the stage of preoperative deformity. Twenty-four patients were completely satisfied with the surgical correction, 6 were satisfied with reservations, and 1 was dissatisfied. The average postoperative AOFAS score for all patients was 85 points (range, 54-100 points), which correlated strongly with patient satisfaction. Twenty-two patients stated that they had no postoperative pain, 8 reported some pain, and 1 had frequent pain at the corrected toe. In 30 feet, there was no recurrence; three patients had mild residual crossover toe deformity, and two patients had recurrent deformity, although all MP joints were stable. Follow-up radiographs demonstrated substantial reduction in MP joint angles in both the AP (from 7 degrees to -1 degree) and lateral (from 45 degrees to 25 degrees) projections. This article reviews the surgical technique of both procedures, proposes specific indications for each, and presents outcomes. Based on our findings, the extensor brevis tendon transfer is appropriate for stage 1, stage 2, and flexible stage 3 deformities. Flexor-to-extensor tendon transfer is appropriate for rigid stage 3 and stage 4 deformities and for all patients with a symptomatic neuroma of the second web space (where the extensor brevis transfer is not possible). Stiffness of the MP joint is a potential problem with the flexor-to-extensor tendon transfer.     

Gefühl ohne Sprache oder Sprache ohne Gefühl? Weitere Hinweise auf die Validität der Entkopplungshypothese der Alexithymie

The theoretical background of the present investigation was the decoupling hypothesis of alexithymia, which presumes for alexithymic individuals a dissociation of psychophysiological indicators of emotion from verbal cognitive awareness of one's emotional state. To study alterations in reactivity to emotionally distressing stimuli in alexithymic individuals, 12 high-alexithymic and 14 low-alexithymic subjects (separated by TAS) out of a general sample of 54 were investigated. All subjects were exposed to cognitive (CPT) and affect inductive (film sequences) distress. During stimulus exposition electrodermal activity (spontaneous fluctuations) was recorded. After stimulus exposition the subjects assessed their emotional reaction towards the film sequences (DAS). Concerning electrodermal activity no differences were found between high and low alexithymics under cognitive distress. In any case a significant autonomous arousal was registered. However, only the low alexithymic subjects but not the high alexithymics showed a significant increase of spontaneous fluctuations as expression of autonomous arousal during presentation of affect inductive stimuli. The altered psychophysiological reactivity found in high alexithymics in contrast to low alexithymic subjects was revealed specifically for the processing of emotional qualified stimuli. However, there was no difference between the groups in cognitive self assessment of emotional response towards the film sequences. The findings are discussed with reference to neurophysiological and psychodynamic models and the decoupling hypothesis of alexithymia.