The control of renin release

An outbreak of histoplasmosis occurred in early May 1970 at a junior high school in Delaware, Ohio; clinical illness occurred in 384 (40 per cent) of the students and faculty, with probably an equal number of subclinical cases. The mode of spread was airborne and was shown epidemiologically to be related to activities on Earth Day, April 22, 1970, when the courtyard in the center of the school, an old bird roost, was raked and swept. Contamination of the entire school building with courtyard air occurred via the school's forced air ventilation system with intakes in the courtyard. Soil samples from the courtyard were positive for Histoplasma capsulatum, but random samples from other areas around the building were negative. In two persons in the building only on April 22, the typical illness developed. Features of the outbreak have important implications for clinicians and public health officials.     

Bypass or amputation?: Concomitant review of bypass arterial grafting and major amputations

In this survey, the results of arterial bypass grafting procedures for occlusive disease and after major amputations have been reported. The two series have been evaluated separately and then some comparisons have been made. The bypass graft series covered risk, mortality, and patency of grafts, including patency at 1 year. The amputation series covered risk, mortality, and effect of previous bypass on the level of amputation, and the ability to ambulate.     

Fatty acids are important for the Frank–Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts

In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine‐palmitoyl‐transferase I (CPT‐I) with oxfenicine (2 mm ). In order to restore fatty acid oxidation, hexanoate (1 mm ), which bypasses CPT‐I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10^?8 and 10^?6 m ). The increase in VV (the Frank–Starling mechanism) increased rate–pressure product (RPP) by 21 ± 2% under control conditions, but only by 6 ± 2% during oxfenicine‐induced CPT‐I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre‐load or flow, whereas the inotropic response to adrenergic β‐receptor stimulation is insensitive to changes in substrate availability.     

Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis,chronic pancreatitis,and pancreatic cancer

Secretory flow rates were measured inside the main pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer and in controls after intravenous administration of secretin. Peak secretory flow rates in these groups were 5.04 ± 1.74, 0.71 ± 1.28, 0.60 ± 1.37, and 4.13 ± 0.88 ml/min, respectively. Peak secretory pressures were also measured intraductally in patients with acute relapsing pancreatitis and pancreatic cancer and in controls and were 402 ± 69, 75 ± 161, and 403 ± 99 mm pancreatic juice, respectively. Peak secretory flow rates and pressures measured in controls during constant administration of secretin were similar to those measured when secretin was administered as a bolus.     

Importance of common bile duct stricture associated with chronic pancreatitis: Diagnosis by endoscopic retrograde cholangiopancreatography

Twenty-one patients with common bile duct strictures associated with chronic pancreatitis are described in whom ERCP was the principal diagnostic method used. In 5 of the 11 patients who had had previous pancreatic or biliary surgery, a common bile duct stricture was overlooked. Nine patients had one or more attacks of cholangitis, which were severe in seven and caused death in one. Endoscopically aspirated bile cultures showed heavy gram-negative infection in four patients with previous cholangitis. Two patients developed stones above the strictures, and in one this led to obstruction of a previous cholecystjejunostomy. Although strictures may be discovered at an asymptomatic stage, there should be careful follow-up to detect the appearance of any symptoms or objective signs of stricture progression, when surgery should be offered without delay. Direct biliary-enteric anastomosis is the procedure of choice when possible to relieve symptoms and prevent the potentially life-threatening complications of cholangitis and septicemia.     

Heart rate affects the dependency of myocardial oxygen consumption on flow in goats

Summary The effect of flow steps in coronary arterial flow (Q_a) on myocardial oxygen consumption (MVo₂) was investigated at different heart rates (HR) to further elucidate the dependency of myocardial oxygen consumption on perfusion. In six anesthetized goats the left main coronary artery and the great cardiac vein were cannulated. The hearts were paced alternately at 60 and 130 beats per min. Flow steps were applied at both HR during control and maximal vasodilation by adenosine. MVo₂, in steady state before and after the flow step, was calculated by multiplication of Q_a and arterio-venous oxygen content difference (Fick's law). Heart rate affected the MVo₂ dependency on flow during control as well as during maximal vasodilation. With vascular tone present, the MVo₂ dependency on flow (MVo₂/Q_a), in µl O₂/ml, was 16.0 ± 3.6 at HR 60 and 21.7 ± 3.9 at HR 130. During maximal vasodilation, these values were 9.5 ± 2.9 and 17.0 ± 5.3 at HR 60 and 130, respectively. The higher MVo₂ dependency on flow at high HR may be explained via a dependency of MVo₂ on microvascular pressure. The pressure change in the microvessels induced by a flow step is probably larger at high HR than at low HR because of increased venous resistance at high HR, due to increased compression by the heart contraction.     

Contractile effects of adenosine, coronary flow and perfusion pressure in murine myocardium

There is mixed evidence adenosine receptors (ARs) may enhance myocardial contractility, although this remains contentious. We assessed inotropic actions of adenosine (50 μM) and selective AR activation with 100 nM N ⁶-cyclohexyladenosine (CHA; A₁AR agonist), 25 nM 2-[p-(2-carboxyethyl) phenethylamino]-5′-N-ethylcarboxamidoadenosine (CGS-21680; A_2AAR agonist) and 100 nM 2-chloro-N ⁶-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA; A₃AR agonist) in mouse hearts perfused at constant pressure, constant flow, or conditions of stable flow and pressure (following maximal nitroprusside-mediated dilatation at constant flow). Adenosine and CGS-21680 significantly (although modestly) increased force in constant-pressure perfused hearts (≤10 mmHg elevations in systolic pressure), effects paralleled by coronary vasodilatation (≤10 ml min⁻¹ g⁻¹ elevations in flow). Neither CHA nor Cl-IB-MECA altered force or flow. With constant-flow perfusion, adenosine and CGS-21680 reduced systolic pressure in parallel with perfusion pressure. When changes in coronary flow and pressure were prevented, CGS-21680 failed to alter contractility. However, adenosine still enhanced systolic pressure up to 10 mmHg. Relations between flow, perfusion pressure and ventricular force evidence substantial Gregg effects in murine myocardium: systolic force increases transiently by approximately 1 mmHg ml⁻¹ min⁻¹ g⁻¹ rise in flow during the first minutes of hyperaemia and in a sustained manner (by ∼1 mmHg mmHg⁻¹) during altered perfusion pressure. These effects contribute to inotropism with AR agonism when flow/pressure is uncontrolled. In summary, we find no evidence of direct A₁ or A₃AR-mediated inotropic responses in intact myocardium. Inotropic actions of A_2AAR agonism appear entirely Gregg-related. Nonetheless, the endogenous agonist adenosine exerts a modest inotropic action independently of flow and perfusion pressure. The basis of this response remains to be identified.     

Gonococcal lipopolysaccharide: A toxin for human fallopian tube mucosa

Gonococci damaged the mucosa of human fallopian tubes in organ culture (FTOC), producing characteristic pathologic features. Filter-sterilized supernatant fluid from donor gonococcal-infected FTOC damaged recipient FTOC in a similar fashion. Gonococcal lipopolysaccharide (LPS) was detected in these toxic donor fluids in concentrations of 1.2 to 8.3 μg/ml. Purified gonococcal LPS in concentrations as low as 0.015 μg/ml produced damage equivalent to that caused by toxic donor fluid and was neutralized by polymyxin B. Such LPS-mediated damage to ciliated cells, if it occurs in gonococcal salpingitis, may impair mucociliary flow and predispose to ectopic pregnancy and recurrent ascending infection.