Radiative Capture on Nuclear Isomers: Direct Measurement of the

We present the first direct measurement of an astrophysical reaction using a radioactive beam of isomeric nuclei. In particular, we have measured the strength of the key 447-keV resonance in the ^{26m}Al(p,γ)^{27}Si reaction to be 432_{-226}^{+146} meV and find that this resonance dominates the thermally averaged reaction rate for temperatures between 0.3 and 2.5 GK. This work represents a critical development in resolving one of the longest standing issues in nuclear astrophysics research, relating to the measurement of proton capture reactions on excited quantum levels, and offers unique insight into the destruction of isomeric ^{26}Al in astrophysical plasmas.

Direct Measurement of Resonances in

We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to ∼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.

Direct Measurement of the Key E_{c.m.}=456 keV Resonance in the Astrophysical

We have performed a direct measurement of the ^{19}Ne(p,γ)^{20}Na reaction in inverse kinematics using a beam of radioactive ^{19}Ne. The key astrophysical resonance in the ^{19}Ne+p system has been definitely measured for the first time at E_{c.m.}=456_{-2}^{+5} keV with an associated strength of 17_{-5}^{+7} meV. The present results are in agreement with resonance strength upper limits set by previous direct measurements, as well as resonance energies inferred from precision (^{3}He, t) charge exchange reactions. However, both the energy and strength of the 456 keV resonance disagree with a recent indirect study of the ^{19}Ne(d, n)^{20}Na reaction. In particular, the new ^{19}Ne(p,γ)^{20}Na reaction rate is found to be factors of ∼8 and ∼5 lower than the most recent evaluation over the temperature range of oxygen-neon novae and astrophysical x-ray bursts, respectively. Nevertheless, we find that the ^{19}Ne(p,γ)^{20}Na reaction is likely to proceed fast enough to significantly reduce the flux of ^{19}F in nova ejecta and does not create a bottleneck in the breakout from the hot CNO cycles into the rp process.

Direct Measurement of the Astrophysical

We have performed the first direct measurement of the ^{38}K(p,γ)^{39}Ca reaction using a beam of radioactive ^{38}K. A proposed ℓ=0 resonance in the ^{38}K+p system has been identified at 679(2) keV with an associated strength of 120_{-30}^{+50} meV. Upper limits of 1.16 (3.5) and 8.6 (26) meV at the 68% (95%) confidence level were also established for two further expected ℓ=0 resonances at 386 and 515 keV, respectively. The present results have reduced uncertainties in the ^{38}K(p,γ)^{39}Ca reaction rate at temperatures of 0.4 GK by more than 2 orders of magnitude and indicate that Ar and Ca may be ejected in observable quantities by oxygen-neon novae. However, based on the newly evaluated rate, the ^{38}K(p,γ)^{39}Ca path is unlikely to be responsible for the production of Ar and Ca in significantly enhanced quantities relative to solar abundances.

Measurement of radiative proton capture on 18F and implications for oxygen-neon novae.

The rate of the 18F(p,γ)19Ne reaction affects the final abundance of the γ-ray observable radioisotope 18F, produced in novae. However, no successful measurement of this reaction exists and the rate used is calculated from incomplete information on the contributing resonances. Of the two resonances thought to play a significant role, one has a radiative width estimated from the assumed analogue state in the mirror nucleus, 19F. The second does not have an analogue state assignment at all, resulting in an arbitrary radiative width being assumed. Here, we report the first successful direct measurement of the 18F(p,γ)^19Ne reaction. The strength of the 665 keV resonance (Ex=7.076 MeV) is found to be over an order of magnitude weaker than currently assumed in nova models. Reaction rate calculations show that this resonance therefore plays no significant role in the destruction of ^{18}F at any astrophysical energy.

Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model.

BACKGROUND AND STUDY AIM: Endoscopic therapy of brisk upper gastrointestinal bleeding remains challenging. A proprietary nanopowder (TC-325) has been proven to be effective in high pressure bleeding from external wounds. The efficacy and safety of TC-325 were assessed in a survival gastrointestinal bleeding animal model. METHOD: 10 animals were randomized to treatment or sham. All animals received intravenous antibiotics, H2-blockers and heparin (activated clotting time 2 × normal). In a sterile laparotomy the gastroepiploic vessels were dissected, inserted through a 1-cm gastrotomy, and freely exposed in the gastric lumen, and the exposed vessel lacerated by needle knife. The treatment group received TC-325 by a modified delivery catheter while the sham group received no endoscopic treatment. Time to hemostasis, and mortality at 60 minutes, 24 hours, 48 hours, and 7 days were noted. Necropsy was performed in all animals. RESULTS: Spurting arterial bleeding was achieved in all animals. No control animal showed hemostasis within the first hour compared with 100 % (5 / 5) in the treatment arm (mean 13.8 minutes, P < 0.0079). Durable hemostasis was achieved with no evidence of rebleeding after 1 and 24 hours in 80 % (4 / 5) of the treated animals compared with none in the control group ( P < 0.0098). None of the control animals survived more than 6 hours. Necropsy at 1 week in treated animals revealed healed gastrotomy without foreign body granuloma or embolization to the lung or brain. CONCLUSION: TC-325 is safe and highly effective in achieving hemostasis in an anticoagulated severe arterial gastrointestinal bleeding animal model.

Direct measurements of ²²Na(p,γ)²³Mg resonances and consequences for ²²Na production in classical novae.

The radionuclide 22Na is a potential astronomical observable that is expected to be produced in classical novae in quantities that depend on the thermonuclear rate of the 22Na(p,γ)23Mg reaction. We have measured the strengths of low-energy 22Na(p,γ)23Mg resonances directly and absolutely using a radioactive 22Na target. We find the strengths of resonances at Ep=213, 288, 454, and 610 keV to be higher than previous measurements by factors of 2.4-3.2, and we exclude important contributions to the rate from proposed resonances at Ep=198, 209, and 232 keV. The 22Na abundances expected in the ejecta of classical novae are reduced by a factor of ≈2.

Changing patterns of ischaemic heart disease mortality in New Jersey 1968-1982, and the relationship with urbanization.

Geographical variations in the declining rates of ischaemic heart disease (IHD) mortality may provide clues about various environmental risk factors responsible as a mass influence on the population IHD rate. The rate of IHD decline in 18 of 21 NJ counties was 2 to 45% less than the USA national rate of decline. The overall decline of IHD mortality in New Jersey (NJ) counties lagged significantly (p less than 0.05 to p less than 0.0003) behind the national trend. Age-adjusted mortality rate (AAMR) for IHD in NJ's 21 counties were 4% to 56% higher than the US rates. The IHD mortality rate of 14 of 21 NJ, counties and the entire state were significantly (p less than 0.005 to p less than 0.000001) above the US rate. Highly urbanized, industrialized, and densely populated NJ counties had the highest IHD rates. In these highly urbanized, industrialized and overcrowded NJ counties the AAMR for IHD was significantly higher and the IHD decline was significantly lower than that in the US. There was a significant (p less than 0.02 to p less than 0.00001) inverse association between annual per capita income and IHD rates. These data suggest that a high degree of urbanization, extensive industrialization, high population density and low socioeconomic status were acting as mass influences on the NJ population IHD rate.

Cryptosporidiosis in an immunosuppressed renal-transplant recipient with IgA deficiency.

Cryptosporidia are sporozoan parasites that infect epithelial cells of the gastrointestinal tract. Infection with cryptosporidia has been found most commonly in a variety of animal species and only rarely in man. The authors report a case of an immunosuppressed renal-transplant recipient with IgA deficiency who experienced diarrhea and fever and was found to have cryptosporidia in a jejunal biopsy specimen and in air-dried smears of the specimen. By electron microscopy, trophozoite, schizont, and macrogamete forms were identified, and these forms ahd morphologic features similar to those of cryptosporidia previously found in guinea pigs. Treatment of the cryptosporidial infection in this case was with trisulfapyrimidines. The efficacy of this treatment could not be evaluated because of complications.

Cardiovascular drug interactions.

Drug interactions may be responsible for certain changes in therapeutic response and toxicity of cardiac drugs. Interactions occur at the sites of drug absorption and elimination as well as at the receptor sites in the pacemaker cells, specialized conducting tissue, and myocardium. Studies of the kinetics of cardiac drugs are being applied clinically in an effort to reduce the danger of adverse drug interactions in heart patients.

The role of furosemide alone and in combination with digoxin in the relief of symptoms of congestive heart failure.

Clinical and cardiovascular responses to drug therapy with furosemide were compared with those to furosemide plus digoxin in 15 heart patients with sinus rhythm admitted to the hospital for the management of congestive heart failure. Except for two patients in the group treated with furosemide alone, who required the addition of intravenous furosemide for more complete relief of symptoms, the responses to the two therapeutic regimens were not significantly different. One patient in the digoxin-treated group developed atrial fibrillation with frequent ventricular premature beats and transient runs of bigeminal rhythm typical of digitalis toxicity, which disappeared as the dose of digoxin was lowered. Side effects were otherwise considered to be minor and similar in the two groups. The results support the view that the indications for digoxin as a positive inotropic agent in patients with congestive heart failure need to be reevaluated.

A decade of developments in diuretic drug therapy.

New diuretics introduced into clinical medicine during the past decade include potent new loop diuretics such as bumetanide and piretanide, the uricosuric indanyloxyacetic acid derivative indacrinone, and a new generation of sulfamoyl diuretics such as indapamide and xipamide, which are recommended primarily for the treatment of hypertension. Pharmacokinetic studies of individual diuretics have demonstrated that the diuretic and natriuretic responses to the newer agents generally follow the plasma drug concentration-time curves and urinary drug excretion rates. Therapeutic monitoring can therefore be achieved in most patients with edema or hypertension by close clinical observation and laboratory analysis of plasma electrolyte and creatinine concentrations and urinary electrolyte excretion rates. Interest in the mechanisms involved in the renal and extrarenal vascular actions of the newer diuretics has led to a better understanding of how changes in venous compliance, peripheral vascular resistance, and renal blood flow distribution may contribute to the overall therapeutic response to these agents, especially in patients with severe congestive heart failure, renal insufficiency with low glomerular filtration rates, and hypertension with cardiorenal complications. Adverse reactions to modern diuretics, which are mainly an extension of their renal pharmacodynamic effects, have proved to be minimal, provided that the dosage is adjusted to meet but not exceed individual patient requirements. However, the long-term consequences of prolonged periods of diuretic-induced alterations in plasma potassium levels, and metabolic effects that include elevated blood lipids, are still under investigation.

Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion.

The purpose of this study was to compare the renal electrolyte excretion pattern of bumetanide with that of hydrochlorothiazide in dogs anesthetized with pentobarbital. In bumetanide-treated animals, mean sodium excretion rose to 12 per cent of the filtered load, while hydrochlorothiazide increased sodium excretion to 4 per cent of the filtered load. After bumetanide, urine pH fell from 6.1 to 5.1 and net hydrogenion excretion increased significantly. After hydrochlorothiazide, urinary pH went from 6.4 to 7.4, and there was no change in net hydrogen ion excretion. Potassium excretion rose to 106+/-22 muEq/min with bumetanide and to 99+/-17 muEq/min with hydrochlorothiazide. These changes in electrolyte excretion occurred despite lack of changes in arterial blood gases, arterial blood pressure, and glomerular filtration rate. In addition, bumetanide did not exert an inhibitory effect on potassium excretion under conditions of potassium loading. It is concluded that bumetanide produces a higher urinary Na+:K+ ratio with a lower pH than hydrochlorothiazide and that renal potassium ion excretion in response to sulfamoyl diuretics is not solely dependent on the rate of sodium excretion.

Clinical use of diuretics in congestive heart failure.

Loop diuretics have become indispensable in the management of patients with cardiac decompensation and severe edema. To evaluate the relative potency of these agents, bumetanide and furosemide were compared in 20 patients with edema associated with congestive heart failure in a double-blind, parallel study design. The dosage of the drugs administered daily for three days was 1 to 2 mg bumetanide or 80 mg furosemide. Both agents were highly effective in reducing the edema and relieving the symptoms of heart failure. Muscle cramps and abdominal pain as side effects were deemed not severe. Laboratory values indicative of mild hypochloremic alkalosis and hyponatremia were observed in two patients. Hypokalemia and reversible eighth-nerve involvement were not apparent in this study.

A computer-based, problem-solving system of instruction in clinical pharmacology.

Advances in microcomputer technology provide new ways of incorporating PBL procedures in clinical pharmacology courses. Developments in graphics-user interfaces and analog/digital systems that display physiologic information directly on the monitor enable the computer to serve as a learning resource as laboratory classes did in the past. A model HyperCard-driven program describes four problem-oriented laboratory exercises that require interpretation and analysis of ECGs. The exercises that involve reading ECGs that were obtained before and after the onset of drug-induced changes in conduction and rhythm are designed to reinforce problem-solving skills in basic electrocardiography and give students a better understanding of the electrophysiologic basis for managing cardiac arrhythmias in clinical practice. For evaluating new programs in medical education, Schmidt describes three conditions that facilitate successful learning; (1) opportunity to use previously acquired knowledge in understanding new information, (2) applicability to future practice, and (3) ability to elaborate on the new information by interaction with other students. Advances that incorporate microcomputer technology and problem-solving learning would receive high scores by such criteria and are recommended by those who are developing courses in clinical pharmacology for medical students and others in the allied health sciences.

Renal electrolyte excretion pattern in response to bumetanide in healthy volunteers.

Renal electrolyte excretion patterns were determined in nonedematous healthy volunteers following bumetanide and furosemide in two separate clinical studies. In study 1, intravenous bumetanide was administered to 24 subjects at four dose levels. In study 2, bumetanide (1 or 2 mg) or furosemide (40 or 80 mg) was administered in a single oral dose to 32 subjects assigned at random to one of the four treatment groups. In study 1, there was a significant dose-related increase in urine volume and sodium, potassium, and chloride excretion, with chloride exceeding sodium at all dose levels, and the Na+/K+ ratios after bumetanide were greater than 3:1. In study 2, the Na+/K+ ratio increased significantly after treatment in all four treatment groups. The relative Na+/K+ ratios showed higher natriuretic potency and lower kaliuretic potency for bumetanide than for furosemide, but the differences were not statistically significant. Additionally, all four treatment groups demonstrated elevation in titratable acidity, ammonia formation, and total acid excretion. There was a significant degree of positive correlation in the bumetanide-treated groups between Na+/K+ and the three variables. In the furosemide-treated groups, this positive correlation was statistically significant between the Na+/K+ ratio and ammonia and total acid secretion but not for titratable acidity. The results support the view that increased H+ formation after the administration of loop diuretics has a relative potassium-sparing effect.

Cutaneous immunoglobulin deposition in primary biliary cirrhosis.

We studied the skin of six patients with primary biliary cirrhosis (PBC) to determine if there is cutaneous deposition of complement and immunoglobulins in PBC. We also investigated serum samples from these patients for the presence of circulating antibodies against nuclear and cytoplasmic antigens. Three of five patients demonstrated immunoglobulins (IgM or IgG) or complement (C3) deposition at the dermoepidermal junction (DEJ) in clinically normal, light-protected skin. Two of six patients had 2- to 5-mm papular-pustular skin lesions as a manifestation of PBC. Serological studies in these patients disclosed low antinuclear antibody titers in three patients and anti-single-stranded DNA antibody titers in the two patients with skin lesions. These histological, immunofluorescent, and serological findings offer further evidence of the occurrence of circulating immune complexes in at least some patients with PBC.

Effect of therapy on bleeding rates in gastrointestinal angiodysplasia.

Sixteen patients with gastrointestinal angiodysplasia requiring transfusion were treated with surgical resection, endoscopic electrocautery, or transfusion alone. Pre- and post-therapy transfusion requirements in each group were compared to gauge the efficacy of each therapy. No superiority of any treatment could be shown statistically. The majority of patients had multiple angiodysplastic lesions throughout the gastrointestinal tract, and, accordingly, complete resolution of bleeding after therapy occurred in fewer than one-half of the patients.

Furosemide and plasma renin activity in essential hypertension.

Changes in arterial blood pressure, renal electrolyte excretion, and plasma renin activity in response to repeated doses of furosemide were measured in 12 patients with essential hypertension admitted to the medical service for electrolyte balance studies. Eighty and 120 mg/day furosemide in divided doses for 5 to 10 days produced a prompt increase in renal sodium excretion. Urinary Na/K concentration ratios, which were elevated during peak natriuresis, returned to control levels following the initial diuretic response. In 2 patients with high initial levels of plasma renin activity, arterial blood pressure was not reduced by furosemide, and more potent antihypertensive agents were required to control the blood pressure. In the remaining patients, furosemide produced a significant decrease in systolic and diastolic blood pressure. There was a general upward shift of plasma renin levels in terms of 24-hour renal sodium excretion in those who demonstrated an antihypertensive response to the drug. However, the average increase in plasma renin activity after repeated doses of furosemide was not statistically significant and no correlation was demonstrated between the level of plasma renin activity after furosemide and the blood pressure lowering effect of the drug.

Esophageal reflux. Diagnosis and therapy.

Diagnosis of esophageal reflux often can be made on the basis of the characteristic symptoms of heartburn and regurgitation. When the picture is not so typical, acid reflux testing and esophageal biopsy appear to be the best indicators of esophageal reflux. Medical management is directed toward preventing reflux, neutralizing refluxed gastric contents, and enhancing clearance of refluxed material. Antacids are a mainstay of therapy, along with restrictions on diet and certain types of activity. If conservative therapy fails to control symptoms and stricture is likely to develop, surgery may be indicated.