Observation of two-neutrino double-beta decay in 136Xe with the EXO-200 detector.

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

Cherenkov light production from the α-emitting decay chains of 223Ra, 212Pb, and 149Tb for Cherenkov Luminescence Imaging.

Cherenkov Luminescence Imaging (CLI) is a new method to image radioactive therapeutic and diagnostic agents, primarily in preclinical studies. This study used Geant4 and Python to generate the predicted Cherenkov light production as a function of time for a set of isotopic chains of interest for targeted alpha therapy: 223Ra, 212Pb, and 149Tb. All are shown to produce substantial Cherenkov light, though time delays between initial decays and the production of Cherenkov light requires caution in interpreting CLI.

Correlation of fingerstick blood glucose measurements with GlucoWatch biographer glucose results in young subjects with type 1 diabetes.

OBJECTIVE: The purpose of this study was to compare measurements of glucose obtained via iontophoretic extraction with the GlucoWatch automatic glucose biographer (Cygnus, Inc., Redwood City, CA) with capillary blood glucose values that were determined 1) in a controlled outpatient clinic setting and 2) in a home setting. RESEARCH DESIGN AND METHODS: There were 76 GlucoWatch biographers used on 28 different young adults (21 women and 7 men) with type 1 diabetes (age 30.9 +/- 6.9 years and duration of diabetes 18.4 +/- 8.1 years [mean +/- SD]) in a controlled outpatient clinic setting. Some subjects participated on multiple days. Subjects wore two GlucoWatch biographers, each on the forearm (ventral aspect). Comparisons were made to HemoCue blood glucose analyzer (Aktiebolgat Leo, Helsingborg, Sweden) capillary blood glucose measurements. In addition, GlucoWatch biographers (one each day for 3 consecutive days) were used by 12 subjects (8 women, 4 men) in a home setting. Comparisons were made to capillary blood glucose values determined using the One Touch Profile meter (Johnson & Johnson, New Brunswick, NJ). RESULTS: GlucoWatch biographer glucose values correlated well with capillary blood glucose values determined using the HemoCue analyzer in the clinic setting (r = 0.90, 1,554 paired data points) and using the One Touch Profile meter in the home setting (r = 0.85, 204 paired data points). When 36 subjects wore two biographers simultaneously, the correlation between the two biographers was r = 0.94. The error grid analysis demonstrated that > 96% of biographer glucose values determined in the clinic or home setting were in the clinically acceptable A and B regions. CONCLUSIONS: This study confirms the accuracy and precision of glucose values as determined using the GlucoWatch biographer in clinic and home settings.

Hereditary continuous muscle fiber activity.

We describe a family with classic features of continuous muscle fiber activity (Isaacs-Mertens syndrome) appearing in an autosomal dominant pattern. Both a mother and her son had muscle stiffness and rigidity in early childhood. Because the mother's condition was not immediately apparent, we recommend a thorough examination of family members.

Analgetic and antiinflammatory 7-aroylbenzofuran-5-ylacetic acids and 7-aroylbenzothiophene-5-ylacetic acids.

A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is 7-[4-(methylthio)-benzoyl]benzofuran-5-ylacetic acid (5g) having 57 times the potency of aspirin in the mouse writhing analgetic assay. This compound caused virtually no gastric ulceration in rats at doses of up to 90 mg/kg.

Bronchodilator and antiulcer phenoxypyrimidinones.

Series of 5-phenoxy-2(1H)-pyrimidinones, 5-phenoxy-4(3H)-pyrimidinones, and related compounds were prepared in a follow-up of a lead prepared as a potential cyclic nucleotide regulating agent. Compounds were evaluated for bronchodilator activity in histamine-challenged guinea pigs and for anticulcer activity in a cold-restraint, stressed rat ulcer model. Bronchodilator activity comparable to, or greater than, that of theophylline was found in both the 2(1H)- and 4(3H)-pyrimidinone series and was most prominent in analogues containing either an electron-withdrawing or -donating substituent in the para position of the phenoxy ring. Significant antiulcer activity was observed only in the 2(1H)-pyrimidinone series among three closely related analogues. One of these, 5-(m-methylphenoxy)-2(1H)-pyrimidinone (3), exhibited more potent antiulcer effects than the clinically useful antiulcer agent carbenoxolone, without demonstrating bronchodilator activity.

Synthesis and antiinflammatory and analgesic activity of 5-aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-ca rboxyl ic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids.

5-Aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carb oxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids were synthesized and assayed as antiinflammatory and analgesic agents. The majority of these compounds exhibit a surprisingly low level of antiinflammatory activity (rat carrageenan paw) but have considerable potency as analgesics (mouse phenylquinone writing). For example, the p-tolyl-substituted bicyclic and monocyclic compounds 44 and 58 are 301 and 66 times more potent than aspirin (mouse writhing) but only 3.4 and 1.5 times more potent than phenylbutazone in the antiinflammatory screen (rat paw).

The technique of primary arterial ligation for cancer of the colon as suggested by venous and lymphatic outflow studies.

Because veins and lymphatics constitute the major pathways for metastatic spread of cancer of the colon, the dynamics of venous and lymphatic outflow from the intestine were studied in dogs with use of electromagnetic flowmeter for the veins and cannulation and gravimetric measurement for the lymph. Venour ligation produced sixfold increases in lymph flow. Venous outflow doubled when adjacent veins were occluded but dropped when marginal vessels were ligated. Simultaneous ligation of arteries and veins caused significant decreases in lymph outflow (to 26% of control), but if arterial collaterals remained intact, lymph flow rose more than twofold. Venous outflow doubled after simultaneous occulusion of adjacent arteries and veins, but dropped as marginal vessels were ligated. Arterial ligation alone was most satisfactory, resulting in significant rapid decreases in lymph flow (to 32% of control) and venous flow (to 5% of control. As suggested by these studies, primary arterial ligation, followed by marginal vessel ligation, is being used as a modification of the "no touch" technique for cancer of the colon.

Massive hemorrhage from ileostomy and colostomy stomas due to mucocutaneous varices in patients with coexisting cirrhosis.

Enterostomal varices have been recognized as a cause of serious recurrent hemorrhage in patients with portal hypertension secondary to cirrhosis. Most often the varices at the mucocutaneous junction are the source of the hemorrhage. Three patients--two with hemorrhages from ileostomies and one with hemorrhages from a colostomy--are presented. Local measures have proved successful in controlling hemorrhages. Occasionally direct pressure alone will prove sufficient; more often the bleeding varix will need ligation. Complete revision of the enterostomy under local anesthesia can effect total disruption of the protal-systemic shunt and temporarily can eliminate local hemorrhage. Surgically created portasystemic shunts may be considered in good risk patients in order to eliminate hemorrhage from the stomal varices. Palliative local measures, however, remain the treatment of choice in the high-risk, cirrhotic patient who is unlikely to survive a major operation.

Evidence that epinephrine acutely redistributes blood flow to experimental intrahepatic tumors.

Tumor microcirculation was studied in Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcoma tumors. Thioflavine S (TS), a fluorescent dye that stains capillary endothelium acutely, was injected intraportally or intra-arterially in order to demonstrate patterns of blood flow through normal liver tissue and through tumor. The dye was given immediately after intraportal injection of 10 micrograms of epinephrine in some animals and 3 minutes after the epinephrine in others. Control animals received TS alone. Additional animals were given TS immediately after intra-arterial epinephrine. The degree of resulting fluorescence in tumor and liver was graded subjectively from 0 to 3+. In the controls and in animals receiving TS 3 minutes after epinephrine, fluorescence in the centers of tumors was absent or, at most, faintly present. In contrast, all animals given epinephrine either intraportally or intra-arterially immediately before the dye showed intense fluorescent staining within the centers of the tumors. Subjective grading averaged 0.6 +/- 0.1 in the controls, 2.2 +/- 0.1 in those receiving intraportal epinephrine immediately before TS, and 1.0 +/- 0.3 in those receiving TS 3 minutes after epinephrine. Results were significantly higher in the latter group (p less than 0.01). Subjective grading in animals receiving intra-arterial epinephrine immediately before TS averaged 2.5 +/- 0.3. These experiments confirm previous studies in this laboratory that demonstrated an acute short-lived redistribution of blood flow into the centers of intrahepatic tumors after administration of epinephrine.

Survival and short-term morbidity of the premature neonate.

Obstetric decisions regarding premature (23 to 32 weeks' gestation) infants must be based on gestational age. However, most reports of the survival of premature infants are based on birth weight. The present report relates the perinatal survival and morbidity of 105 newborns to the obstetric gestational dating criteria between 23 and 32 weeks' gestation. Gestational age was determined from at least four obstetric criteria including the first day of the last menstrual period, early pelvic examination, the earliest auscultation of fetal heart tones with a fetoscope, fundal height measurements in centimeters between 20 and 30 weeks' gestation, and sonographic gestational age measurements. At 23 to 26 weeks' gestational age, nine (39%) of 23 neonates survived. Five of nine survivors had moderate to severe intracranial hemorrhage, three had moderate to severe bronchopulmonary dysplasia, and three had moderate to severe retrolental fibroplasia. At 27 to 29 weeks' gestational age, 25 (93%) of 27 neonates survived. Of the 25 survivors, three had moderate to severe intracranial hemorrhage, one had moderate to severe bronchopulmonary dysplasia, and one had severe retrolental fibroplasia. At 30 to 32 weeks' gestational age, 52 (95%) of 55 neonates survived. Three of the 52 (6%) survivors had serious neonatal morbidity consisting of moderate to severe intracranial hemorrhage (three neonates) and moderate to severe bronchopulmonary dysplasia (one neonate). Thus, ten of 34 (29%) survivors between gestational ages of 24 to 29 weeks had a serious morbidity versus only three of 52 (6%) survivors between 30 to 32 weeks' gestation (P less than .01).

Perforated appendicitis in an incarcerated inguinal hernia.

Although perforated appendicitis in an incarcerated hernia is an uncommon condition, the clinical manifestations vary from relatively benign to much more serious, depending on whether the septic process is limited to the hernial canal and sac or if there is intraperitoneal contamination. The patient described in this report had minimal symptoms other than a slightly tender, irreducible inguinal hernia. He easily tolerated resection of the appendix and contiguous inguinal tissues, with a primary repair of the inguinal hernia.

Enterostomal varices secondary to portal hypertension: progression of disease in conservatively managed cases.

A follow-up of patients with portal hypertension who were bleeding from enterostomal varices in ileostomies or colostomies demonstrated the progression of disease and poor prognosis. Repeated episodes of hemorrhage became more frequent, liver function deteriorated, and death from hepatic failure finally occurred. The hemorrhagic episodes seemed to contribute to the deterioration of the patients' conditions. Portasystemic shunting to eliminate enterostomal bleeding should be considered for the patient who is an acceptable operative risk. If major surgery is contraindicated, local hemostatic measures offer, temporarily, palliative alleviation of bleeding, but the ultimate prognosis is grave.

Cholecystectomy in patients with mild cirrhosis. A more favorable situation.

A conservative approach toward elective cholecystectomy in the patient with cirrhosis has been suggested because of the strong likelihood of excessive bleeding, sepsis, and multiple organ failure. We reviewed this problem in two medical centers, studying 27 patients with cirrhosis who had undergone nonemergency biliary tract surgery. Most patients had adequate liver function preoperatively. Most operations were cholecystectomies without duct exploration. Among factors analyzed were liver function tests, coagulation tests, and Child's classification. Prothrombin time was less than 2.5 s above control in 18 patients, more than 2.5 s above control in four patients, and not recorded in five patients. All survived the operation with benign postoperative courses. Only one patient had excessive bleeding; this patient had an elevated prothrombin time preoperatively. We conclude that elective cholecystectomy can be performed safely in patients with cirrhosis who have relatively normal liver function.

Enhancement of tumor blood flow and tumoricidal effect of doxorubicin by intraportal epinephrine in experimental liver metastasis.

Laser Doppler capillary perfusion monitoring was performed in 25 Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcomas. Doses of intraportal epinephrine from 1 to 10 micrograms produced an immediate rise in capillary blood flow, reaching peak levels by 16 s. The increased flow lasted an average of 57 s. Because epinephrine selectively increased tumor blood flow, studies were performed to determine if enhancement of the chemotherapeutic effect of doxorubicin could be achieved. Forty-two rats with seven-day hepatic implants were treated sequentially with intraportal epinephrine (10 micrograms) and doxorubicin hydrochloride (10 mg/kg) or doxorubicin alone. After only two courses of chemotherapy, a significant difference in necrosis and cell viability was obtained in those animals treated with epinephrine intraportally prior to doxorubicin infusion. Enhancement of the tumoricidal effect of chemotherapy can be achieved by manipulating the blood flow to developing tumors pharmacologically.

Second hepatoma developing 13 years after resection of first tumor.

A patient underwent a left-sided hepatic lobectomy for primary hepatocellular carcinoma 13 years ago and remained symptom free. He then presented with spontaneous rupture of a large tumor in the right lobe of the liver. Although this tumor proved to be primary hepatocellular carcinoma, there were significant histological differences between the two lesions, suggesting that this was a second primary liver tumor. Bleeding from the tumor was controlled by selectively ligating the branches supplying the area of hemorrhage.

The effects of histamine and serotonin on polymorphonuclear leukocyte accumulation in the rat.

Histamine and serotonin were evaluated for their effects on rat polymorphonuclear leukocyte (PMN) accumulation in vivo and PMN migration in vitro. Both of the mediators inhibited the accumulation of PMNs when injected into the pleural cavity in a saline vehicle, and reduced the PMN content of the peripheral blood. Histamine also reduced the cellular influx when administered in combination with an intrapleural injection of carrageenan. Peripheral blood leukocytes removed from rats injected intrapleurally with histamine and carrageenan had a lesser chemotactic responsiveness compared with those removed from rats injected only with carrageenan. The effects of histamine in reducing PMN accumulation was abolished by treatment with cimetidine, an H2 antagonist, but not by treatment with chlorpheniramine, an H1 antagonist. These results suggest that a local release of histamine may play a role in reducing cellular infiltration into an inflammatory site.

The "tip-of-the-tongue" phenomenon in aphasia.

Forty-two male aphasics, classified as Broc's, Wernicke's, anomic, and conduction, were examined for their ability to partially retrieve acoustic features of words they could not provide in a confrontation naming task (the "tip-of-the-tongue" phenomenon). The results indicated that conduction aphasics were superior to Wernicke's and anomic asphasics in their ability to identify both the first letter and the syllabic length of the words they could not name. Since the aphasic groups were comparable in their naming difficulty, the findings could not be attributed to degree of wordfinding impairment. The difference between groups that were obtained using the TOT technique are discussed with regard to differences in the word finding process.

Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer.

BACKGROUND: Improved glycemic control significantly reduces long-term microvascular complications of diabetes mellitus associated with chronic hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive diabetes management by providing automatic, frequent, and noninvasive glucose readings up to three times per hour for as long as 12 hours. METHODS: The device extracts glucose through intact skin using reverse iontophoresis and measures the extracted glucose with an electrochemical biosensor. A clinical trial was performed to assess the effect of acetaminophen, a potential interference for traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in adult subjects with diabetes (n = 18). One thousand milligram doses of acetaminophen were administered to subjects in two groups: one to achieve Cmax (peak acetominophen concentration) at the time of biographer calibration and the other to achieve Cmax during the measurement period. The biographer readings were compared to serial fingerstick blood glucose measurements. RESULTS: Time profiles over 9 hours show close tracking of the biographer glucose results with fingerstick blood glucose measurements for all groups. The mean difference between the two measurements is between 8 and 12 mg/dL for all groups. The mean absolute value of the relative difference is less than 20%, and more than 93% of the points were in the clinically acceptable (A+B) region of the Clarke Error Grid. No statistically significant differences were found for any accuracy measurement across all groups. CONCLUSIONS: The GlucoWatch Biographer provides frequent measurements of glucose over a 12-hour period with high accuracy. No effect of therapeutic dosage of acetaminophen on the accuracy of the glucose readings was found.

Primary arterial ligation in resection of cancer of the colon. Rational and technic.

The dynamics of arterial, venous, and lymphatic flow in the mesentery were studied in dogs, using an electromagnetic flowmeter for the blood and cannulation and gravimetric measurement for the lymph. Ligation of veins caused an increased venous outflow in adjacent veins and a marked increase in lymph flow. When marginal vessels were ligated, eliminating the major collateral flow, venous flow decreased, but elevated lymph flow persisted. Simultaneous ligation of arteries and veins resulted in increases of both arterial and venous flow in adjacent vessels. Lymph flow decreased unless excessive arterial collateral flow persisted. When collateral marginal vessel flow was occluded, adjacent venous and arterial blood flow decreased to control levels. With arterial ligation, collateral arterial blood flow increased slightly, but venous and lymph flow decreased sharply. When collateral marginal vessels were eliminated, adjacent arterial blood flow decreased to control levels and venous flow virtually stopped. As a result of these studies, the technic of early primary arterial ligation followed by marginal vessel ligation appears to be the most satisfactory procedure for decreasing venous and lymphatic outflow and hopefully avoiding dissemination of cancer cells during the operation. This technic is now being used as a modification of the "no touch" technic for cancer of the colon.