Ca2+ channel actions of the non-dihydropyridine Ca2+ channel antagonist Ro 40-5967 in vascular muscle cells cultured from dog coronary and saphenous arteries

Summary We studied the membrane effects of (1S,2S)-2-(2-[[3-2(benzimidazolyl) propyllmethylamino]ethyl)-6-fluoro-1,2,3,4-tetrahydro-l-isopropyl-2-naphthyl-methoxy-acetate dihydrochloride, Ro 40-5967, a new non-dihydropyridine (DHP) Ca²⁺ channel antagonist, on dog coronary and saphenous arterial vascular muscle cells using the whole-cell patch-clamp method. Long-lasting (L-type) inward currents in 20 mM Ba²⁺ were measured over a range of test potentials (300 ms) from –50 mV to + 90 mV from a holding potential of –80 mV in the presence of 1 M Bay k8644 (a DHP Ca²⁺ agonist). Ro 40-5967 caused a concentration-dependent suppression of Ca²⁺ channel currents in muscle cells from both arteries, with greater potency on coronary than saphenous arterial cells. The concentration of Ro 40-5967 which inhibited the magnitude of peak inward currents by 50% (IC₅₀) was estimated to be 1 M (n = 5) in muscle cells from coronary artery and 10 M (n = 4) in saphenous artery. Ro 40-5967 (1 M) decreased the amplitude of the activation current-voltage relationship for coronary L-type Ca²⁺ channel currents over a wider range of membrane potentials than verapamil, diltiazem, or nifedipine. In contrast, block of Ca²⁺ channel currents in saphenous artery cells by 1 M Ro 40-5967 was only observed at command potentials positive to 0 mV. Ro 40-5967 (1 M) significantly shifted the voltage-inactivation curve downward by 40% in coronary (n = 4), but only by 18% in saphenous arterial muscle cells (n = 3). The non-parallel shift of the coronary artery inactivation curve suggests that pronounced resting channel block is a notable feature of Ro 40-5967. The marked inhibition of Ba²⁺ current by 1 M Ro 40-5967 in the inactivation protocol in coronary arterial muscle cells was found over the entire range of membrane holding potentials tested, while inhibition in the saphenous artery inactivation curve occurred only from holding potentials more positive than –40 mV. Therefore, Ro 40-5967 is unique: 1) in acting over a wider range of voltages, on both instantaneous and resting Ca²⁺ currents, than other Ca²⁺ antagonists; 2) in producing more significant resting state block; and 3) in acting with selectivity for coronary over saphenous arteries.This research was supported by National Institutes of Health grants HL38537, HL38645, and by F. Hoffmann-La Roche, Basel, Switzerland     

Can parturients distinguish between intravenous and epidural fentanyl?

We tested the hypothesis that the sedative, euphoric, and analgesic effects of intravenous fentanyl would distinguish intravenous from epidural administration. One hundred ASA I and II labouring parturients received 100 μg fentanyl either iv or via an epidural catheter in a double-blind, randomized, crossover fashion. Nineteen anaesthetists (8 staff and 11 residents) participated and correctly guessed the route of administration of the fentanyl in 61/66 intravenous doses and in 69/75 epidural doses yielding a sensitivity of 92.4%, a specificity of 92.0%, a positive predictive value of 91.0%, and a negative predictive value of 93.2%. Of the 41 patients that were crossed over, 38 (92.7%) were able to detect a difference between the routes of administration. Most patients experienced prompt, short-lived symptoms with iv fentanyl but no important differences in fetal heart rate pattern or in maternal desaturation were seen between the groups. This study suggests that subjective symptoms will accurately distinguish intravenous from epidural fentanyl administration in labouring parturients (P < 0.001), and should serve as a safe and reliable intravenous test dose for epidural anaesthesia in the obstetric population.     

Information technology in dental education

The use of information technology in dental education is continually increasing. In this article, IT is defined, and its uses in teaching and learning explored. Examples of the appropriateness of multimedia teaching in dental education are given. Successful multimedia teaching, especially in clinical settings, relies on the proper use of IT and an implementation strategy. The applications of IT to curriculum development, computer-assisted learning (CAL), educational administration, dental practice, hospital administration, and clinical research are also considered.     

Changes in hemodynamics of the carotid and middle cerebral arteries before and after endoscopic sympathectomy in patients with palmar hyperhidrosis: preliminary results

OBJECT: The purpose of this study was to analyze the change in carotid and middle cerebral artery (MCA) hemodynamics before and after endoscopic upper thoracic sympathectomy in patients with palmar hyperhidrosis (PH). METHODS: Sixty-eight patients with PH (35 males and 33 females) for whom the average age was 24.5+/-10.7 years (+/- standard deviation) were recruited into this study. These patients all underwent routine upper T-2 sympathectomy to treat their PH. Ultrasonography studies of the carotid arteries (CAs) and MCA were obtained in each patient before and after T-2 sympathectomy. The blood flow volume, flow velocity, and resistivity index (RI) in the bilateral common CAs (CCAs), internal CAs (ICAs), and external CAs (ECAs) were evaluated using duplex ultrasonography. The systolic peak velocity, mean velocity, diastolic peak velocity, pulsatility index, and RI of the bilateral MCAs were evaluated using transcranial Doppler ultrasonography. Blood pressure and heart rate were also recorded during this study. The Student paired t-test was used to analyze the differences between studies before and after bilateral T-2 sympathectomy. There was a significant reduction in diastolic pressure after T-2 sympathectomy (p = 0.003), but not in systolic pressure or heart rate. The vessel diameter was increased after sympathectomy in the left CAs and right CCA. The T-2 sympathectomy led to significant elevation of blood flow volume and RI in the left CCA, ICA, and ECA (p < 0.05). The authors found significant increases in maximum flow velocity and RI in the left MCA (p < 0.05). CONCLUSIONS: Patients who underwent T-2 sympathectomy demonstrated a significant increase in blood flow volume and flow velocities of the CAs and MCA, especially on the left side. Asymmetry of sympathetic influence on the hemodynamics of the CAs and MCA was noted. The usefulness of sympathectomy for the treatment of ischemic cardiovascular and cerebrovascular disease deserves further investigation.     

Spontaneous oscillations of cerebral blood flow velocity in the middle cerebral arteries of normal subjects and schizophrenic patients

Although many regional cerebral blood flow (rCBF) studies of schizophrenic patients have been carried out, only a few studies have investigated real-time hemodynamic changes in schizophrenic patients. In the present study, we used long-term monitoring of the middle cerebral artery (MCA) by non-invasive transcranial Doppler ultrasonography to obtain real-time CBF data in 55 schizophrenic patients and 20 normal comparison subjects. The mean blood flow velocity and pulsatility index (PI) of the MCA were not constant during long-term monitoring. They showed sinusoidal oscillations similar to those described in previous reports. The amplitude variations of these oscillations in both drug-naive and medicated schizophrenic patients were significantly decreased compared with findings in normal control subjects. The averaged PI values were found to be decreased in patients with illness durations of more than 10 years. After withdrawal of antipsychotic medication, both the amplitude variations of oscillations and the PI values in the drug-withdrawn patients were significantly decreased relative to findings in normal control subjects. Our results show a decreased adjustment ability of cerebral vessel resistance not only in neuroleptic-naive schizophrenic patients but also in patients with longer illness duration. Neuroleptics could affect the adjustment ability of vessel resistance.     

Post-steroid elevations of intraocular pressure in patient after radial keratotomy

PURPOSE: The evaluation of frequency and amplitude of IOP elevations in patients after RK who were administrated topically dexamethasone. MATERIAL AND METHODS: RK was carried out in 90 eyes (55 patients). All these patients had been treated topically with 0.1% dexamethasone (Maxitrol, Alcon) since the first day after surgery till the period of 3 months in lowering doses. IOP was measured using air-puff tonometer (Reichert, USA) before surgery and on 1, 2, 3, 14, 30, 50, 90 day after RK. In case of IOP elevations the measurements were made more often. RESULTS: The mean IOP before surgery was 14.88 +/- 2.86 mm Hg for women and 16.14 +/- 2.83 mm Hg for men. In the period of 3 months after RK maximum IOP increased significantly both for women (mean: 21.46 +/- 7.51 mm Hg) and men (mean: 26.14 +/- 8.87 mm Hg). IOP higher than 25 mm Hg was observed in 35 eyes (37.7%). These IOP elevations were observed more often in men than women but this difference was not statistically significant. There was no correlation between frequency of IOP elevations and preoperative refractive error or the age of patients. CONCLUSIONS: The usage of steroids after RK requires careful monitoring of IOP. This subject needs further studies to answer if these IOP elevations can damage eye functions.     

Matrix Metalloproteinase Inhibitors: Applications in Oncology

Matrix metalloproteinases (MMP) are a group of zinc dependentenzymes which include the interstitial collagenases, stromelysins,gelatinases and membrane-type metalloproteinases. They are involvedin the remodelling and turnover of the extracellular matrixproteins. They play a role in wound healing and the pathogenesis ofarthritis. In malignancies they play a role in tumor invasion,metastasis and angiogenesis. A number of synthetic matrixmetalloproteinase inhibitors (MMPIs) have been developed forclinical use. In preclinical tumor models they have shown promisingactivity in achievinginhibition of MMPs and reducing tumor growth and metastatic spread.Some have also shown additive or synergistic effects with cytotoxicagents. Phase I and II studies in human subjects have defined themain side effects of these agents as beingmusculoskeletal pains or arthralgias. As they are cytostatic agentsrather than cytotoxic in activity conventional measurements ofradiological response for assessment are not applicable in trials.Biological activity has been demonstrated in certain cancers by theeffects on levels of tumor markers as surrogate markers of tumorresponse and also by a fibrotic stromal reaction seen in tumortissue. Newer agents have been developed withselective inhibition of certain MMPs in an attempt to reduce theside effects. A number of phase III human clinical trialsevaluating MMPs are being carried out at present but onlyone has been formally reported so far. This study suggested thatmarimastat had no survival advantage when compared to chemotherapywith gemcitabine in advanced pancreatic carcinoma. Current trialsare assessing efficacy of MMPIs in maintenance of remission afterother modalities of therapy or in combination with cytotoxicagents. MMPs have also been demonstrated to play an important rolein the articular cartilage destruction seen in both rheumatoidarthritis and osteoarthritis. The use of MMPIs in both exvivoand in vivomodels have shown promising resultsand trials are in process to assess their potential role in thecontrol of articular destruction. The true therapeutic role ofMMPIs await the results of these randomized studies.     

Serum lipid & lipoprotein profiles of obese Chinese children

The serum lipid and lipoprotein levels of 59 obese Chinese children with a mean age of 13.0 years and mean relative weight of 164.2% were analysed. Between 40% to 54% of these children had elevated lipid and lipoprotein levels and about 78% had reduced high density lipoprotein (HDL) level when compared to healthy American and Japanese children. The obese children also had higher mean levels of total cholesterol (TC) and lower HDL compared to male adults in the local population. Those with elevated TC had higher mean relative weight (170% vs 159%, p < 0.05). In view of the close association between hyperlipidaemia and atherosclerosis, obese children should be carefully screened and managed to prevent long term morbidity and mortality of coronary artery disease.     

Analysis of the place of regulation of C-11 transmitters at the Tele-electronic Works "Telkom-Telfa" in Bydgoszcz from the point of view of visual hygiene]

The authors performed a detailed analysis of 100 positions of regulation of the C-11 transmitters in the "Telcom-Telfa" ++Tele-electronic Works in Bydgoszcz. It was determined that the requirements for the condition of the eyes and the lighting at this workstand are considerable. Conclusions and recommendations tending to improvement of the working conditions are drawn up. Proposed is eventual rationale leading to the reduction of the eyestrain and facilitation of the work.