Physiologic-pharmacologic interpretation of the constants in the Hill equation for neuromuscular block: a hypothesis

Neuromuscular block (NMB) is simulated in pharmacodynamic models using the concentration of a muscle relaxant (MR) in the effect compartment and two constants, and IC50. No physiologic or pharmacologic interpretation is offered for either constant. We desired to explore whether the constants are properties of the muscle or the MR and to simulate NMB when the MR binds to two sites at a single receptor. Based on steady state conditions, we defined receptor occupancy using the equilibrium dissociation constants. Two concepts are introduced: threshold occupancy and occupancy at half-maximal NMB, Occ_NMB50. Threshold occupancy is defined as receptor occupancy at the motor end plate of a muscle fiber when the fiber fails to contract and Occ_NMB50 as the median threshold occupancy. NMB may be simulated as a function of either the concentration of the muscle relaxant or receptor occupancy. We suggest: (1) The distribution of threshold occupancies is an intrinsic property of a muscle and is characterized by two constants (_O and Occ_NMB50); (2) _O is numerically equal to the slope of the NMB vs. concentration curves and is independent of the equilibrium dissociation constants. IC50 is codetermined by Occ_NMB50 and by the equilibrium dissociation constants. (3) Binding of a muscle relaxant to the second binding site influences only the estimate of IC50 but not .     

Effects of morphine on oedema and tissue concentration of nerve growth factor in experimental inflammation of the rat paw

Injection of carrageenan (1 mg) into the rat hind paw caused a time-dependent increase in paw volume that was maximal 3 h after injection. At this time, the concentration of nerve growth factor (NGF) in the skin of the inflamed paw was more than twofold higher than in the contralateral, non-inflamed paw. Treatment of rats with indomethacin reduced inflammatory oedema by 57%, morphine treatment attenuated oedema by 62%. While indomethacin had no statistically significant effect on the concentration of NGF in the skin of inflamed paws, morphine attenuated the NGF response by 24.2% in a naloxone reversible manner. These data suggest that drug-induced inhibition of inflammatory oedema is not predictive of its effect on an inflammation-induced rise in tissue NGF. Furthermore, our results confirm and extend previous observations suggesting an anti-inflammatory activity of morphine.     

Sperm-bound amidase activity as a marker for acrosomal integrity in bull spermatozoa

An assay for sperm-bound amidase activity was validated using bovine spermatozoa and N-benzoyl-DL-arginine p-nitroanilide as substrate. The assay had intra- and interassay coefficients of variations of 5 and 12%, respectively. It is an inexpensive, simple and rapid assay since 100 samples can be evaluated in 2 hours and it requires only 4 X 10(6) spermatozoa per sample. Sperm-bound amidase activity was proportional (r = 0.95) to the percentage of spermatozoa with an intact acrosome, as determined by differential interference-contrast microscopy. A change of five percentage units in the incidence of damaged spermatozoa was detectable. Using this procedure, assessment of sperm-bound amidase activity is therefore a sensitive and efficient means of evaluating acrosomal integrity.     

Rapid and accurate stability-indicating assay for nitroglycerin.

A rapid high-pressure liquid chromatographic method for determining the nitroglycerin concentration in liquid dosage forms and intravenous admixture solutions is presented. A coefficient of variation of less than 1.8% was achieved over the concentration range most commonly encountered (50-500 microgram/ml). A variable wavelength detector (lambda = 218 nm) and a micro-alkyl phenyl column were employed. The mobile phase was acetonitrile-tetrahydrofuran-water (26:10:64). Total analysis time was 12 min.     

Fibropolycystic diseases of the liver and bile ducts--a case report and review of the literature

A case of congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease) is reported. This 20-year-old patient presented also with congenital hepatic fibrosis, fusiform dilatation of the common bile duct and cysts of the liver parenchyma, accompanied by medullary sponge kidneys. The dominant clinical feature was recurrent septic cholangitis. Clinical picture, as well as the diagnostic and therapeutic problems of the individual entities of hepatobiliary fibropolycystic disease are discussed. Although these belong to a family of closely related malformations, whereby involvement of different anatomic levels varies from case to case, such a complex combination as in this patient has not, to our knowledge, been reported before.     

Fatal air embolism in an extremely low birth weight infant: can it be caused by intravenous injections during resuscitation?

OBJECTIVE: A preterm infant with a birth weight of 384 g who succumbed to vigorous resuscitation for sudden respiratory failure on the third day of life is presented. Postmortem examination revealed, apart from extensive pulmonary hemorrhage, a fatal amount of air mainly in the right ventricle. We believe that this air had been introduced via peripheral venous cannulas due to inadvertent and unavoidable air admixture to each injection volume administered with a syringe, and we develop an experimental model to confirm that fatal amounts of air can indeed accumulate with frequent change over of syringes within a short period of time. DESIGN: An empty 50-ml syringe was connected to a 15-cm-long connection line via a three-way tap. With a 1 ml syringe 100 doses of 0.5 ml aqua were injected into the connection line. The amount of air which had collected in the 50 ml syringe after the 100 injection cycles was measured. This process was repeated three times each by three of the authors and the average air volume introduced with 100 injections calculated for each investigator. RESULTS: The average amounts of air which had entered the closed system after 100 acts of syringe assembly and aqua administration were 1.84, 1.95, and 2.0 ml. This corresponds to an average volume of almost 0.02 ml per injection.     

Kalziphylaxie

Calciphylaxis is a rare disease which has been increasingly reported in recent decades and has consequently shifted into the focus of clinical and scientific research. The clinical picture is characterized by extensive ischemic ulcerations of the skin and subcutis. Histologically, the small vessels in these lesions show prominent calcifications. Due to the extensive areas of ulceration and necrosis as well as frequently present comorbidities, patients with calciphylaxis are prone to infection and sepsis. In this work, we describe the case of a female kidney-transplant patient with vasculitis who, despite good graft function, developed a fulminant calciphylaxis of both thighs 4 years post transplantation and died of septic complications. The differential diagnoses as well as clinical procedures are described in detail in the case history. In the discussion, we give an overview of the current state of knowledge regarding the etiopathogenesis, risk factors, diagnostic measures and clinical management of calciphylaxis.     

Significance of Group III and IV muscle afferents for the endurance exercising human

With the onset of dynamic whole-body exercise, contraction-induced mechanical and biochemical stimuli within locomotor muscle cause an increase in the discharge frequency of thinly myelinated (Group III) and unmyelinated (Group IV) nerve fibres located within the muscle. These thin fibre muscle afferents project to various sites within the central nervous system and thereby substantially influence the exercising human. First, Group III/IV muscle afferents are the afferent arm of cardiovascular and ventilatory reflex responses that are mediated in the nucleus tractus solitarius and the ventrolateral medulla. Therefore, neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O(2) delivery determine the fatigability of skeletal muscle. Second, Group III/IV muscle afferents facilitate 'central fatigue' (failure, or unwillingness, of the central nervous system to 'drive' motoneurons) by exerting inhibitory influences on central motor drive during exercise. Thus, Group III/IV muscle afferents play a substantial role in a human's susceptibility to fatigue and capacity for endurance exercise.