Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."

BACKGROUND In response to rising rates of opioid abuse and overdose, U.S. states enacted laws to restrict the prescribing and dispensing of controlled substances. The effect of these laws on opioid use is unclear. METHODS We tested associations between prescription-opioid receipt and state controlled-substances laws. Using Medicare administrative data for fee-for-service disabled beneficiaries 21 to 64 years of age who were alive throughout the calendar year (8.7 million person-years from 2006 through 2012) and an original data set of laws (e.g., prescription-drug monitoring programs), we examined the annual prevalence of beneficiaries with four or more opioid prescribers, prescriptions yielding a daily morphine-equivalent dose (MED) of more than 120 mg, and treatment for nonfatal prescription-opioid overdose. We estimated how opioid outcomes varied according to eight types of laws. RESULTS From 2006 through 2012, states added 81 controlled-substance laws. Opioid receipt and potentially hazardous prescription patterns were common. In 2012 alone, 47% of beneficiaries filled opioid prescriptions (25% in one to three calendar quarters and 22% in every calendar quarter); 8% had four or more opioid prescribers; 5% had prescriptions yielding a daily MED of more than 120 mg in any calendar quarter; and 0.3% were treated for a nonfatal prescription-opioid overdose. We observed no significant associations between opioid outcomes and specific types of laws or the number of types enacted. For example, the percentage of beneficiaries with a prescription yielding a daily MED of more than 120 mg did not decline after adoption of a prescription-drug monitoring program (0.27 percentage points; 95% confidence interval, −0.05 to 0.59). CONCLUSIONS Adoption of controlled-substance laws was not associated with reductions in potentially hazardous use of opioids or overdose among disabled Medicare beneficiaries, a population particularly at risk.

These gamma rays have also been observed from magnesium in the present experiment.

No abstract

In areflexic canine right heart bypass preparations, little difference in ventricular function was observed as a result of atrial pacing, sequential atrioventricular pacing, or atrial-His bundle pacing at an appropriate atrial systole-ventricular systole (As-Vs) interval. Ventricular function was depressed during ventricular pacing and during atrioventricular pacing with an inappropriate As-Vs interval. In areflexic isovolumic left ventricle preparations, ventricular function was depressed during ventricular pacing compared to atrial pacing, and changes in the As-Vs interval during atrioventricular pacing were accompanied by changes in ventricular function only in association with changing patterns of ventricular activation. In animals with heart block under conditions of right heart bypass, wherein changes in the pattern of ventricular activation were precluded during atrioventricular pacing, ventricular function deteriorated pari passu with shortening of the As-Vs interval. These data indicate that both the temporal relation between atrial and ventricular contraction and the pattern of ventricular activation importantly influence ventricular function during cardiac pacing. The marked changes in ventricular function observed as a function of the As-Vs interval, for any given pattern of electrical activation, suggest that the As-Vs interval is the more important determinant of ventricular function during cardiac pacing.

Sarcoidosis is a chronic systemic granulomatous disease that occasionally affects the larynx. When the degree of involvement is marked, significant airway obstruction can occur. We present four cases of laryngeal sarcoidosis that resulted in airway obstruction. The clinical features of sarcoidosis of the larynx are discussed, and current methods of treatment are summarized. The laryngologist should include laryngeal sarcoidosis in the differential diagnosis of patients with airway obstruction, and should play a major role in its management.

DECAY M EASU RE M EN TS I N EM ULS ION ON PARTI CLES the nucleus may have been sufficient to cause (PvXy. )observed tO he OPPOStte tO (PZXPv)at production. This would have tended to mask any effect that might have been present. ACKNOW'LED GMENTSWe wish to express our appreciation and indebtedness: To Dr. Joseph J. Murray and his co11eagues for providing the separated E-meson beams, and to Dr. Edward J. Lofgren and the Bevatron crew for their cooperation and aid in the exposures. participation in the design and assembly of the equipment for magnetic analysis of beams, and for their help in various phases of the analyses.To all the scanners involved in this program and particula, rly to Miss Ernestine Beleal, Alan 8etz, Mrs. Marilyn O'I ollin, Mrs. Penny Vedder, and Mrs. Hester Yee for considerable assistance with the measurements and calculations.To i4Irs. Penny Vedder for much of the programming and aid with the IBM 650 computations.To James Hodges for constructing, and participating in the design of, the automated microscopes, and to Thomas Taussig for designing the associated electronics.A beam of Xs mesons was produced by passing a beam of 1.1-Bev/c negative pions through a liquid hydrogen target and accepting the neutral reaction products in the forward direction after allowing the X& component to decay. The resultant beam was observed in a 30-in. propane bubble chamber 6tted with lead and iron plates. About 200 regenerated IC1 mesons were identi6ed by their characteristic Q value and decay rate. All three types of regeneration were observed: by transmission in the plates, by nuclear di8raction, and by interaction with single nucleons. The detection of the erst two types of regeneration constitutes strong evidence for the correctness of the Gell-Mann and Pais particle mixture theory. Comparison of the transmission and diffraction regeneration e8ect, using the method of M. L. Good, gives the E~-Xg mass difference B. Two important corrections must be applied to Good's formula: One originates from the nuclear scattering of the transmission component, the other from the multiplicity of scatterings in a thick plate.The independence from nuclear parameters, which was an advantageous property of Good's formula, is no longer rigorously valid; but due to the sharp dependence of the transmission intensity upon the mass difference, the nuclear properties of Eo and Xo, as derived from E'+ and X data, still allow a measurement, of 8. We find that 5 is 0.84 s, ss+'ss in units of k/rip where rr is the Er mean lifetime. With 90% confidence level, the diiference is between 0.44 and 1.2 k/rr. The probability that the transmission peak we observe is due to a statistical fluctuation is one in a million.

A B S T R A C T The coronary vasoconstrictor properties of digitalis were evaluated in 61 anesthetized, openchest dogs after coronary sinus cannulation and under conditions of a constant heart rate (atrioventricular pacing) and near-constant blood pressure. The contribution of alpha adrenergic receptor stimulation to the digitalisinduced increase in coronary vascular resistance (CVR) was examined. With Na pentobarbital anesthesia (16 dogs), intravenous acetylstrophanthidin (0.5 mg) caused a significant (P < 0.05) rise in CVR from 1 through 9 min after injection. The peak increase was + 11±2% SE of the control of 1.8±0.2 mm Hg/cm3/min. The mean time to peak effect was 3 min, and to recovery was 21 min. Prior alpha adrenergic receptor blockade with phenoxybenzamine in 11 animals reduced (P < 0.05) the acetylstrophanthidin-induced peak of CVR and substantially decreased (P < 0.05) the time to recovery (5 min). Intravenous digoxin (1.0 mg) with Na pentobarbital anesthesia (five dogs) had no significant effect on CVR. However, with chloralose and urethane anesthesia (nine dogs) the same dose of digoxin produced a significant rise in CVR from 3 through 30 min. The peak increase was +20±3% of control (1.4±0.1 mm Hg/cm3/ min). One-third the dose of intravenous digoxin (0.35 mg) produced a 9.5±1.0% increase in CVR (five additional dogs). Myocardial oxygen consumption did not change significantly in nine dogs after intravenous digoxin. In 10 additional dogs pretreated with phenoxybenzamine and in 7 dogs pretreated with mecamylamine, the increase in CVR did not occur after 1.0 mg of intravenous digoxin. Thus there is a coronary vasoconstrictor effect of intravenous acetylstrophanthidin and digoxin, Preliminary report of data presented at the 56th Annual Meeting of the Federation of American Societies for Experimental Biology, 1972. (Fed. Proc. 31: 597. Abstr.) Received for publication 28 February 1973 and in revised form 10 August 1973.of rapid onset, which is mediated through alpha adrenergic receptor stimulation. INTRODUCTIONA direct vasoconstrictor effect of digitalis has been established in a number of organ systems (1, 2) and has been postulated for the heart (3). Recently, a neurogenic vasoconstrictor effect of digitalis, mediated through alpha adrenergic receptor stimulation, has been described in resting skeletal muscle (4); the magnitude of this effect is substantially greater than the direct effect of the drug (4). These findings coupled with the demonstration of the existence of alpha adrenergic receptors in the coronary vasculature (5, 6) suggest that digitalis might have a neurogenic vasoconstrictor effect in the heart. The purpose of this communication is to present data documenting the existence of a neurogenic coronary vasoconstriction produced by both acetylstrophanthidin and digoxin. The data also characterize the time course and magnitude of this effect.