A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man

Objective　To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. Methods　The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results　Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion　A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation.     

Large cell carcinoma of the lung: a highly aggressive tumor with dismal prognosis

A retrospective review was made of 96 consecutive patients with large cell carcinoma of the lung admitted to Emory University Hospital over 10 years. Only 10 patients were seen with stage I lesions favorable for resection. The remainder were treated primarily with irradiation or chemotherapy. Mean survival for clinical stage I patients was 15.9 months; stage IIIA patients, 7.9 months; stage IIIB patients, 7.1 months; and stage IV patients, 5.8 months. Only 1 patient survived for 5 years. This distinct and highly aggressive form of lung cancer most commonly is seen at an advanced stage and is associated with an unusually dismal prognosis regardless of the method of treatment employed.     

Did a Goals-of-Care Discussion Happen? Differences in the Occurrence of Goals-of-Care Discussions as Reported by Patients,Clinicians, and in the Electronic Health Record

Context

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

Progressive dyspnea associated with a crazy-paving appearance on a chest computed tomography scan

A ‘crazy-paving’ appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information.     

The inability of isoproterenol or propranolol to alter the lateral dimensions of experimentally induced myocardial infarcts

Summary The relationship between the blood flow pattern immediately following coronary artery occlusion and the resulting infarct 24 hours later was studied in dogs treated with isoproterenol (0.5 g/kg/min for 2 hours) or with propranolol (2mg/kg every 6 hours). The coronary artery of a closed chest dog was perfused via a special cannula with arterial blood. A 2-mm diameter plastic bead was introduced into the perfusate to embolize a coronary branch. One minute after occlusion, radiolabelled microspheres were injected into the perfusate. The dogs were then allowed to recover. 24 hours later the dogs were reanesthetized and their hearts removed. The hearts were sliced into 4 mm thick sections and the microsphere distribution was visualized by autoradiography of the tissue. Superimposition of developed autoradiographs and tracings of the infarct pattern of stained sections allowed direct comparison of the blood flow pattern immediately after occlusion to the eventual pattern of infarction. In all 8 control dogs, all 6 isoproterenol dogs and all 12 propranolol dogs the lateral borders of blood flow and infarction were superimposable indicating no lateral change in infarct size resulting from treatment. In the control group there was a subepicardial region of the ischemic zone which did not infarct (15.2±2.3% of the ischemic zone). Though isoproterenol did not significantly change the size of this zone, propranolol increased it to 35.9±6,5% (p<0.005) indicating vertical but not lateral salvage.Supported by Grant HL-20648 from NIH: HLBI and a Grant-in-aid from the American Heart Association and with funds contributed in part by the Northwest Ohio Chapter, Inc.     

Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial K(ATP) channels

It has been assumed that all G(i)-coupled receptors trigger the protective action of preconditioning by means of an identical intracellular signaling pathway. To test this assumption, rabbit hearts were isolated and perfused with Krebs buffer. All hearts were subjected to a 30-minute coronary artery occlusion followed by 120 minutes of reperfusion. Risk area was measured with fluorescent particles and infarct size with triphenyltetrazolium chloride staining. Control hearts showed 29.1+/-2.8% infarction of the risk zone. A 5-minute infusion of acetylcholine (0.55 mmol/L) beginning 15 minutes before the 30-minute occlusion resulted in significant protection (9.2+/-2.7% infarction). This protection could be blocked by administration of 300 micromol/L N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, or by 200 micromol/L 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) antagonist, for 15 minutes beginning 5 minutes before the acetylcholine infusion (35.2+/-3.9% and 27.8+/-2.4% infarction, respectively). Similar protection was observed with other known triggers, ie, bradykinin (0.4 micromol/L), morphine (0.3 micromol/L), and phenylephrine (0.1 micromol/L), and in each case protection was completely abrogated by either MPG or 5-HD. In contrast, protection by adenosine or its analog N(6)-(2-phenylisopropyl) adenosine could not be blocked by either MPG or 5-HD. Therefore, whereas most of the tested agonists trigger protection by a pathway that requires opening of mitochondrial K(ATP) channels and production of free radicals, the protective action of adenosine is not dependent on either of these steps. Hence, it cannot be assumed that all G(i)-coupled receptors use the same signal transduction pathways to trigger preconditioning.     

Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.