Development of Chronomers tm for narcotic antagonists

The object of this program is to prepare a bioerodable naltrexone delivery system which can be implanted subcutaneously in humans and which can relieve the narcotic antagonist over 1-6 months at relatively constant and sufficient rates to block the euphoric effect of morphine based drugs. The system is composed of naltrexone uniformly dispered in a solid hydropholic CHRONOMER TM matrix which undergoes predictable surface erosion when exposed to an aqueous medium. Kinetic studies in vitro have been carried out during the course of the program to determine the best composition for the system. Toxilogical studies conducted at ALZA during the past 2 years have not revealed limiting adverse effects of either the CHRONOMER TM materials or their hydrolysis products. The tail-flick test procedure was used to measure the effectiveness of naltrexone to antagonize the analgesis of morphine in rats. Naltrexone infused intravenously at doses of 4 and 16 ug/kg/hr resulted in, after 6 hours, 54 and 89% antagonism, respectively, against a 63.5% effective dose of morphine. Perliminary sterilization studies showed that no adverse effects to CHRONOMER TM/naltrexone systems occurred after exposure to 2.5 or 5.0 mrads of 60CO irradiation.     

Evaluation of the Del Mar Avionics automatic ambulatory blood pressure-recording device

We have the opportunity to evaluate a portable ambulatory device for the recording of sequential indirect arterial blood pressure and continuous electrocardiogram (Del Mar Avionics automatic ambulatory blood pressure recording device). With careful attention to technique, only 11% of systolic and 5% of diastolic blood pressure readings differed by more than 10 mm Hg as compared with a trained technician's observations simultaneously in the same arm. The device has been useful in the evaluation of borderline (labile) hypertension, hypertensive drug therapy programs, and various episodic cardiovascular phenomena--for example, vasodepressor syncope and pheochromocytoma crises.     

Infarct sizing with technetium-99m stannous pyrophosphate scintigraphy in dogs and man; relationship between scintigraphic and praecordial mapping estimates of infarct size in patients

The dynamics of changes in serum lipids (free fatty acids, free glycerol, triglycerides, total cholesterol, and phospholipids) were studied in male Wistar rats irradiated in an open experimental field with a daily dose of 15.48 mC.kg.--1 (60 R) up to a total exposure of 774.0 mC. kg.--1 (3,000 R). The resulting changes occurred in several periods. Initial period of 0--7 days included a drop in triglyceride level and a rise in free glycerol, total cholesterol, and phospholipids in both control and irradiated rats. The period of 14--25 days marked the appearance of serum hyperlipaemia. Between 25--50 days, the levels of the different fractions oscillated and existing changes became more pronounced. The general level of serum lipids during continuous gamma-irradiation exceeded that found in controls. Changes in control animals from experimental field reflected the influence of a changed environment. The modifying factor affecting both irradiated and control rats was night fasting prior to sacrificing the animals and, probably, also the presence of an infradian rhythm in some serum lipid fractions.     

Toxic effect of systemic administration of low doses of the plasticizer di-(2-ethyl hexyl) phthalate [DEHP] in rats

A spreadsheet model of a circle breathing system and a 70-kg anaesthetised 'standard man' has been used to simulate the first 20 min of low-flow anaesthesia with halothane, enflurane, isoflurane, sevoflurane and desflurane in oxygen. It is shown that, with the fresh-gas flow set initially equal to the total ventilation and the fresh-gas partial pressure to 3 MAC, the end-expired partial pressure can be raised to 1 MAC in 1 min with desflurane and sevoflurane, 1.5 min with isoflurane, 2.5 min with enflurane and 4 min with halothane. Sequences of lower fresh-gas flow and partial pressure settings are given for then maintaining 1 MAC end-expired partial pressure, with a minimum usage of anaesthetic, e.g. 13 ml of liquid desflurane in 20 min (of which only 33% is taken up by the patient) if the minimum acceptable flow is 11.min-1, or 8 ml (with 57% in the patient) if the minimum is 250 ml.min-1.     

Probabilistic analysis of functional magnetic resonance imaging data

Probability theory is applied to the analysis of fMRI data. The posterior distribution of the parameters is shown to incorporate all the information available from the data, the hypotheses, and the prior information. Under appropriate simplifying conditions, the theory reduces to the standard statistical test, including the general linear model. The theory is particularly suited to handle the spatial variations in the noise present in fMRI, allowing the comparison of activated voxels that have different, and unknown, noise. The theory also explicitly includes prior information, which is shown to be critical in the attainment of reliable activation maps.     

Age changes in cells in Streptococcus diacetilactis cultures

The activity of metabolism changed in the cultures of Streptococcus diacetilactis, strain Bogdan, with aging. The number of viable cells decreased as well as the ability to evolve oxygen, to produce C-4 compounds, and to react to pH changes by liberating acids upon alkalifying or neutral products upon acidifying. After the culture had been grown during 72 hours, 2,3-butyleneglycol was found in the cultural broth, and the number of viable cells was low. As was revealed by electron microscopy, the cells were intact during 48 hours; they started to disintegrate by 72 hours. After 120 hours all cells were disintegrated. First, the cells produced no more mesosomes, became less electron dense; then the cell wall was decomposed and the contents of the cell poured through disruptions in the cytoplasmic membrane.