Voltage dependence of the pattern and frequency of discrete Ca2+ release events after brief repriming in frog skeletal muscle

Applying a brief repolarizing pre-pulse to a depolarized frog skeletal muscle fiber restores a small fraction of the transverse tubule membrane voltage sensors from the inactivated state. During a subsequent depolarizing test pulse we detected brief, highly localized elevations of myoplasmic Ca²⁺ concentration (Ca²⁺ “sparks”) initiated by restored voltage sensors in individual triads at all test pulse voltages. The latency histogram of these events gives the gating pattern of the sarcoplasmic reticulum (SR) calcium release channels controlled by the restored voltage sensors. Both event frequency and clustering of events near the start of the test pulse increase with test pulse depolarization. The macroscopic SR calcium release waveform, obtained from the spark latency histogram and the estimated open time of the channel or channels underlying a spark, exhibits an early peak and rapid marked decline during large depolarizations. For smaller depolarizations, the release waveform exhibits a smaller peak and a slower decline. However, the mean use time and mean amplitude of the individual sparks are quite similar at all test depolarizations and at all times during a given depolarization, indicating that the channel open times and conductances underlying sparks are essentially independent of voltage. Thus, the voltage dependence of SR Ca²⁺ release is due to changes in the frequency and pattern of occurrence of individual, voltage-independent, discrete release events.     

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.     

Universities as resources to state health agencies.

In a survey of the 50 State health agencies in the spring of 1992, officials were asked about their manpower and research needs in the specific areas of administration, behavioral and social science, education and information, environmental health, environmental protection, epidemiology, laboratory, law, occupational health, policy and planning, and statistics. In all, 40 agencies (80 percent) responded. Indepth telephone interviews to determine whether universities and schools and graduate programs in public health filled these needs completed the data collection process. Agency officials indicated that their resources were least adequate in environmental protection, behavioral and social science, and occupational health. They did not feel their research needs were being met. There was a general feeling that universities and schools and programs in public health have different agendas than State agencies and that practical solutions to the shortage of research resources are not forthcoming from these sources. Suggestions are made as to what can be done to improve relationships between those who train public health personnel and those who employ them.     

Percutaneous transluminal angioplasty (PTA) of the deep femoral artery.

Between 1979 and 1988 43 percutaneous transluminal angioplasties (PTA) of the deep femoral artery were performed for treatment of severe claudication (n = 15) or for limb salvage (n = 28). Ateriographically, all patients had a long occlusion of the superficial femoral artery. Additional PTA of significant obstructions in the iliac and common femoral artery were performed in 6 patients of each group. Technical success was achieved in 41 of the 43 procedures (95%). Early clinical success was 60% for claudicants and 68% for patients with limb threatening ischemia. Success rates tended to be higher if additional PTA of the inflow tract was performed (75% versus 61%, n.s.). Patient with a good distal outflow benefited more frequently from PTA if they were treated for limb salvage (p less than 0.05). Within a follow-up period up to 24 months (mean 18.0 months) 5 patients died and one late failure occurred. Life table analysis lasting success in patients dilated for limb salvage, whereas success rate decreased to 48% in claudicants. PTA of the deep femoral artery is a less invasive and efficient treatment particularly for patients with limb threatening ischemia, an appropriate obstruction morphology provided.     

RA-spezifische Autoantikörper gegen ein 68k-Antigen

Zusammenfassung Die Diagnostik vieler rheumatischer Systemerkrankungen wird heute durch den Nachweis von Autoantik?rpern unterstützt und erleichtert. Für die Serodiagnostik der Rheumatoiden Arthritis (RA) stehen nur die doch wenig spezifischen Rheumafaktoren zur Verfügung. Mit dem Ziel, neue krankheitsspezifische Autoantik?rper nachzuweisen, erfolgte eine besondere Proteinaufarbeitung aus Synovialisbiopsien und anderen Geweben. Western Blots der gewonnenen Proteine wurden eingesetzt, um Seren von RA-Patienten und solchen mit anderen rheumatischen Erkrankungen zu untersuchen. Die signifikanteste Immunreaktion von RA-Patienten richtete sich gegen ein 68k-Antigen, welches vermutlich ubiquit?r exprimiert wird, da es nicht nur in Synovialis, sondern in allen weiteren untersuchten Humangeweben und HeLa-Zellen nachgewiesen werden konnte. Der isoelektrische Punkt liegt bei 5,1, das Protein ist O-glykosyliert und im endoplasmatischen Retikulum und/oder Cytoplasma lokalisiert. Antik?rper gegen dieses 68k-Antigen waren bei 110 von 167 RA-Patienten nachzuweisen, was einer Sensitivit?t von 66% entspricht. Ihr Vorkommen war unabh?ngig vom Rheumafaktornachweis, da sie auch bei 7 von 12 seronegativen RA-Patienten zu finden waren, dagegen nur bei einem Patienten aus einer Kontrollgruppe von 98 Patienten mit anderen rheumatologischen Krankheitsbildern, bei einem von 22 HIV-Patienten und überhaupt nicht bei 55 Gesunden. Daraus resultiert eine RA-Spezifit?t für diesen Antik?rper von 99%. Wegen der auff?lligen Krankheitsspezifit?t der anti-68k-Antik?rper liegt es nahe, nach korrespondierenden autoreaktiven T-Zellen zu suchen, um die Rolle dieser neuen Autoreaktivit?t in dem Pathomechanismus der RA zu analysieren. Eingegangen: 20. Mai 1996 Akzeptiert: 13. Februar 1997     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

“Helper:” A critical events prompter for unexpected emergencies

Objective. The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment.Methods. The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group).Results. A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p=0.015); similarly MgSO₄ was appropriately ordered more often in the experimental group (p=0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p=0.004), and epinephrine infusion was ordered for refractory bradycardia (p=0.002) more often in the experimental than the control group.Conclusions. These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.This study was made possible by a grant from the Anesthesia Patient Safety Foundation. Results were presented, in part, at the meeting of the STA/SEA Orlando, Florida, January 1994.