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In this study, cDNA for a somatostatin receptor variant (somatostatin receptor subtype 2, SSTR 2) was isolated, cloned, and sequenced from rainbow trout. A 1821-nt cDNA was isolated and found to contain a single initiation site 387-nt from the most 5' end, an open reading frame of 1116-nt, and a single putative polyadenylation site 189-nt from the most 3' end. The encoded protein contains 372 amino acids and contains seven membrane-spanning domains. Based on structural analysis, the protein was identified as a subtype 2 SSTR. These data support the emergence of a multigenic SSTR family early in the course of vertebrate evolution, concomitant with or perhaps prior to the divergence of boney fish. The distribution of SSTR 2 mRNA in tissues was determined by quantitative real time-PCR (QRT-PCR). SSTR 2 was most abundant in the brain (where it was detected in the telencephalon, optic tectum, and hypothalamus), skeletal muscle, and liver, but it also was present in the endocrine pancreas (Brockmann body) and various regions of the gastrointestinal tract (esophagus, stomach, intestine). SSTR 2 mRNA was most abundant in the brain, muscle, and liver. In vitro the Brockmann body and liver with increasing concentrations of glucose (1, 4, 10mM) resulted in increased expression of SSTR 2 mRNA. These findings contribute to the understanding of the evolution of the SSTR family and provide insight into the roles of SSTR 2 in fish. more...

Postnatal decreases in vascular reactivity involve decreases in the thick filament component of myofilament calcium sensitivity, which is measured as the relationship between cytosolic calcium concentration and myosin light chain (MLC20) phosphorylation. The present study tests the hypothesis that downregulation of thick filament reactivity is due to downregulation of myosin light chain kinase (MLCK) activity in adult compared with fetal arteries. Total MLCK activity, calculated as %MLC20phosphorylated per second in intact arteries during optimal inhibition of myosin light chain phosphatase activity, was significantly less in adult (6.56 ± 0.29%) than in fetal preparations (7.39 ± 0.53%). In situ MLC20concentrations (μM) in adult (198 ± 28) and fetal arteries (236 ± 44) did not differ significantly. In situ MLCK concentrations (μM), however, were significantly greater in adult (8.21 ± 0.59) than in fetal arteries (1.83 ± 0.13). In situ MLCK activities (ng MLC20phosphorylated·s−1·ng MLCK−1) were significantly less in adult (0.26 ± 0.01) than in fetal arteries (1.52 ± 0.11). In contrast, MLCK activities in adult (15.8 ± 1.5) and fetal artery homogenates (17.3 ± 1.3) were not significantly different. When in situ fractional activation was calculated, adult values (1.72 ± 0.17%) were significantly less than fetal values (9.08 ± 0.83%). Together, these results indicate that decreased thick filament reactivity in adult compared with fetal ovine carotid arteries is due at least in part to greater MLCK activity in fetal arteries, which in turn cannot be explained by differences in MLCK, MLC20, or calmodulin concentrations. Instead, this difference appears to involve age-related differences in fractional activation of the MLCK enzyme. more...

Background ERCP is usually performed with the patient in the prone position. Little data exist on ERCP in the supine position, which is considered unsafe in nonintubated patients. Objective Our purpose was to compare outcomes of ERCP in the prone and supine positions. Design Retrospective study. Setting Tertiary care medical center. Patients All patients undergoing ERCP by one endoscopist over an 18-month period. Main Outcome Measurements American Society of Anesthesiologists (ASA) score, procedural degree of difficulty, procedural time, success rates, complication rates, effects on oxygen desaturation and hemodynamics, amount of sedation, need for precut sphincterotomy. Results A total of 649 patients were evaluated, of whom 506 patients were prone and 143 were supine. There were no differences between the groups with regard to sex, procedural time, ASA scores, need for precut sphincterotomy, adverse cardiovascular events, episodes of oxygen desaturation, dose of meperidine or midazolam, or oxygen supplementation. Complete success and complication rates were similar for both groups (90.2% and 11.2% for supine and 92.5% and 9.1% for prone, respectively). Procedural degree of difficulty was significantly higher in the supine group ( P Limitations Retrospective study, one endoscopist. Conclusions ERCP performed in nonintubated patients placed supine is often more difficult and may lead to more mild adverse respiratory events than when performed with the patient prone. Supine ERCP is appropriate in certain patients who cannot lie prone (abdominal pain, abdominal distention, ascites, recent abdominal or neck surgery, indwelling percutaneous tubes and need for access during the procedure to indwelling internal/external percutaneous biliary catheters, and in the morbidly obese) with more intensive monitoring in those who are not intubated. more...

It has been reported that sensitization of animals to allergens increases both early shortening velocity and myosin light-chain kinase of their airway smooth muscle without increasing force generated by these muscles. Since early shortening sets muscle length for the duration of a contraction, these responses might be expected to produce greater airway obstruction. Here, it is explained how the more rapid early shortening without increased force production is predicted by the 2-stage process of activation followed by contraction posited by the crossbridge theory of contraction when the rate, but not the extent, of activation is increased. The experimental results are reproduced by a simple model in which activation rate is increased 1.6-fold without any other changes in contractile parameters. These results reinforce suggestions that sensitized animals are a model for reactive airway disease. more...

Muscle birefringence, caused mainly by parallel thick filaments, increases in smooth muscle during stimulation, signalling thick filament formation upon activation. The reverse occurs in skeletal muscle, where a decrease in birefringence has been correlated with crossbridge movement away from the thick filaments. When force generation by trachealis muscle was inhibited with wortmannin, which inhibits myosin light-chain phosphorylation and thick-filament formation, but not the calcium increase caused by stimulation, the birefringence response inverted, suggesting crossbridge movement similar to that of skeletal muscle. Resistance to quick stretches was much greater in stimulated muscle than in unstimulated muscle before wortmannin treatment and no different in stimulated and unstimulated muscle after force inhibition by wortmannin. Before wortmannin treatment, stimulation reduced thick-filament cross-sectional areas in electron micrographs by 44%. After force inhibition by wortmannin, filament areas were not significantly different in stimulated and unstimulated muscle and not significantly different from those of relaxed muscle without wortmannin treatment. These results suggest that myofibrillar-space calcium causes crossbridges to move away from the thick filaments without firmly attaching to thin filaments. more...

asthma affects 17.7 million Americans, 5 million of them children ([41][1]). Its incidence has more than doubled in the general population since 1980, with a disproportionate increase in children under the age of 4 ([41][1]). Measures of the yearly burden of this disease, 5,500 deaths ([31][2]) more...

Background A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. Methods Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. Results Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% ( PConclusions The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity. more...

The outpatient treatment of heart failure can be divided into 2 broad categories: older therapies, which improve hemodynamics, and newer therapies, which increase survival and improve function. Hemodynamic "triple" therapy includes digoxin to increase cardiac inotropy, antihypertensives to lower systolic pressure, and diuretics to remove fluid and decrease filling pressures. Disease-modifying therapy requires the use of specific agents to lower blood pressure (angiotensin-converting enzyme inhibitors, angiotensin II blockers, spironolactone, or hydralazine and nitrates) and beta-adrenergic blockade with carvedilol. The success of these newer therapies suggests that the standard triple therapy for heart failure should be expanded to "quadruple" therapy that includes carvedilol. more...

Although environmental estrogens (EE) have been found to disrupt a wide variety of developmental and reproductive processes in vertebrates, there is a paucity of information concerning their effects on organismal growth, particularly postembryonic growth. In this study, we exposed juvenile rainbow trout (Oncorhynchus mykiss) to 17β-estradiol (E2) β-sitosterol (βS), or 4-n-nonylphenol (NP) to assess the effects of EE on overall organismal growth and on the growth hormone-insulin-like-growth factor (GH-IGF) system. EE treatment significantly reduced food conversion, body condition, and body growth. EE-inhibited growth resulted from alterations in peripheral elements of the GH-IGF system, which includes multiple GH receptors (GHRs), IGFs, and IGF receptors (IGFRs). In general, E2, βS, and NP reduced the expression of GHRs, IGFs, and IGFRs; however, the effects varied in an EE-, tissue-, element type-specific manner. For example, in liver, E2 was more efficacious than either βS, and NP in reducing GHR expression, and the effect of E2 was greater on GHR 1 than GHR2 mRNA. By contrast, in gill, all EEs affected GHR expression in a similar manner and there was no difference in the effect on GHR1 and GHR 2 mRNA. With regard to IGF expression, all EEs reduced hepatic IGF1 and IGF2 mRNA levels, whereas as in gill, only E2 and NP significantly reduced IGF1 and IGF2 expression. Lastly, E2 and NP reduced the expression of IGFR1A and IGFR1B mRNA expression similarly in gill and red and white muscle, whereas βS had no effect on expression of IGFR mRNAs. These findings indicate that EEs disrupt post-embryonic growth by reducing GH sensitivity, IGF production, and IGF sensitivity. more...

Malignant biliary obstruction results in jaundice, often with symptoms that decrease the quality of life. Biliary stent placement has largely supplanted surgical bypass for palliation of malignant biliary obstruction. Traditional rigid plastic stents are commonly used, inexpensive and easily removed, although with limited duration of stent patency. Self-expandable metal stents (SEMS) attain larger luminal diameters and provide longer patency than traditional rigid plastic stents in patients with distal bile duct obstruction. SEMS are composed of a variety of metals and can be uncoated, partially covered, or fully covered. Data do not support a prolongation of patency with covered SEMS for distal obstruction, although they have the potential for removability. The data to support SEMS for palliation of hilar biliary obstruction are not as convincing and reintervention for stent occlusion can be difficult. In this article, the design and performance of expandable metal stents for treatment of malignant biliary obstruction will be reviewed. more...

The shortening velocities of single, skinned, fast and slow skeletal muscle fibers were measured at 5-6 degrees C in five animal species having a 25,000-fold range of body size (mouse, rat, rabbit, sheep, and cow). While fiber diameter and isometric force showed no dependence on animal body size, maximum shortening velocity in both fast and slow fibers and maximum power output in fast fibers were found to vary with the -1/8 power of body size. Maximum power output in slow fibers showed a slightly greater (-1/5 power) dependence on body size. The isometric force produced by the fibers was correlated (r = 0.74) inversely with fiber diameter. For all sizes of animal the average maximum velocity was 1.7 times faster in fast fibers than in slow fibers. The large difference in mechanical properties found between fibers from large and small animals suggests that properties of the contractile proteins vary in a systematic manner with the body size. These size-dependent changes can be used to study the correlations of structure and function of these proteins. Experimental results also suggest that the different metabolic rates observed in different sizes of animals could be accounted for, at least in part, by the difference in the properties of the contractile proteins. more...

Zenker's diverticulum (ZD) is the most common type of diverticulum in the upper gastrointestinal tract. Most patients are elderly and present with symptoms of dysphagia. Serious complications include aspiration and malnutrition. The most common treatments are open surgical diverticulectomy with or without cricopharyngeal myotomy and rigid endoscopic myotomy. Recently, cricopharyngeal myotomy using flexible endoscopes has been described as a treatment option for symptomatic ZD. In this article we describe the pathophysiology, clinical presentation and review the techniques and outcome following flexible endoscopic management of Zenker's diverticulum. more...

Endoscopic biliary sphincterotomy (ES) is the cornerstone of therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Bleeding is one of the most frequent complications following ES. Rates of post-ES bleeding vary widely and its presentation may be immediate (intraprocedural) or several days later. Clinically, bleeding can range from insignificant to life threatening. Most bleeding episodes are managed successfully by conservative measures with or without endoscopic therapy. Endoscopic treatment options include injection, thermal, and mechanical methods-alone or in combination. For refractory cases, angiographic embolization, or surgery, is necessary. Both technical risk factors and patient risk factors contribute to the development of post-ES bleeding. When these risk factors are present, measures can be taken to reduce the risk of bleeding. In this manuscript the literature on post-ES bleeding is reviewed. more...

Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored. more...

To assess activation mechanisms of dog trachealis muscle and test whether isometric force generation could be separated from myosin light-chain (MLC) phosphorylation, force and phosphorylation were measured in the presence of wortmannin (a light-chain kinase inhibitor) or Y-27632 (a rho-kinase inhibitor) during electrically stimulated tetani and sustained contractures induced by acetylcholine, KCl, or calyculin A, a light-chain phosphatase inhibitor which caused irreversible contractures and both di- and mono-phosphorylation of light chain. Phosphorylation was not much more than half under any circumstances. A nearly constant proportionality between steady force and phosphorylation existed over a 9-fold force range during contractures and 25-sec tetani, except that force correlated best with the di-phosphorylated light chain produced by calyculin A. Phosphorylation was disproportionately higher than force at the outset of tetani, and this disproportion was exaggerated by Y-27632. The results suggest that about half the light chain is sequestered from kinases and that mechanical activation is tightly linked to phosphorylation, except at the outset of stimulation. more...

To assess factors that limit human muscle strength and growth, we examined the relationship between performance and body dimensions in the world weightlifting champions of 1993–1997. Weight lifted varied almost exactly with height squared (Ht2.16), suggesting that muscle mass scaled almost exactly with height cubed (Ht3.16) and that muscle cross-sectional area was closely correlated with body height, possibly because height and the numbers of muscle fibers in cross section are determined by a common factor during maturation. Further height limitations of muscle strength were shown by only one male champion ≥183 cm and no female champions ≥175 cm. The ratio of weight lifted to mean body cross-sectional area was approximately constant for body-weight classes ≤83 kg for men and ≤64 kg for women and decreased abruptly for higher weight classes. These findings suggest a nearly constant fraction of body mass devoted to muscle in lighter lifters and a lesser fraction in heavier lifters. Analysis also suggests that contractile tissue comprises ∼30% less body mass in female champions. more...

those of us who pursue biological research do so mainly because of the intellectual satisfaction derived from making discoveries. But we are blessed with generous grants from our governments whose motivations are more practical and include improving the health of our populations, promoting new more...

“idiopathic” acute pancreatitis due to biliary sludge: prevention of relapses by endoscopic biliary sphincterotomy in high-risk patients

Expanding on the 1989 National Research Council volume AIDS, Sexual Behavior, and Intravenous Drug Use, this book reports on changing patterns in the distribution of cases and the results of intervention efforts under way. It focuses on two important subpopulations that are becoming more and more at risk: adolescents and women. The committee also reviews strategies to protect blood supplies and to improve the quality of surveys used in AIDS research.AIDS: The Second Decade updates trends in AIDS cases and HIV infection among the homosexual community, intravenous drug users, women, minorities, and other groups; presents an overview of a wide range of behavioral intervention strategies directed at specific groups; discusses discrimination against people with AIDS and HIV infection; and presents available data on the proportion of teenagers engaging in the behaviors that can transmit the virus and on female prostitutes and HIV infection. more...

Twelve normal subjects, 50 patients with valvular heart disease, and 14 with hypertension were studied. Those with valvular disease were divided into two groups: 28 with angiographically measured ejection fractions greater than or equal to 0.6 and 22 with ejection fractions less than 0.6. The echocardiographically measured ventricular thickness divided by radius ratio (t/r) was approximately proportional to peak systolic pressure (P) in all groups having ejection fractions greater than or equal to 0.6, so that the t/r divided by P ratios were nearly the same. Patients with ejection fractions less than 0.6 had significantly lower t/r divided by P values. No single component of the t/r divided by P ratio would identify the patients with lower ejection fractions. The t/r divided by P ratios in 14 hypertensive patients were nearly identical to the ratios in six patients with aortic stenosis and ejection fractions greater than or equal to 0.6, indicating that an aortic valve gradient does not cause a grossly abnormal form of pressure hypertrophy. The t/r ratio is thus a double sensitive, noninvasive index of dilation when correlated with systolic pressure. more...

It is well known that corrected acuity in ametropia is usually normal, or approximately so, but is sometimes markedly reduced. In many cases this low acuity occurs in eyes which appear normal, even to careful examination. Often the corrected acuity differs markedly in the two eyes; for example, one may be 20/15 and the other 20/40. In some cases unequal acuity is known to be associated with unequal refraction or anisometropia. Anisometropia, it is generally agreed, presents difficult problems of correction. Many writers have speculated regarding the possible relations of corrected acuity to refractive conditions, but satisfacory statistical analyses are lacking. The clinical importance of the problems, particularly in the correction of anisometropia in children, justifies a reexamination of the question with material selected to present those refractive conditions mentioned. The present study is an attempt to apply adequate statistical analysis to appropriate data. SOURCE OF DATA AND TERMINOLOGY The more...

ARAPID, accurate, and sensitive method is needed for the bioassay of hypophyseal thyrotropic hormone (TSH). Borell, in 1945, demonstrated an increase in total phosphorus content of the thyroid gland following stimulation with TSH. This observation led Borell and Holmgren in 1949 to the use of radioactive phosphorus (P32) uptake of the thyroid of the guinea pig as an indicator of TSH activity. Later, Crooke and Matthews (1953), and Lamberg (1953), presented bioassay methods utilizing P32 uptake of the one day old chick. This report describes modifications in the radiophosphorus uptake methods which increase the accuracy and sensitivity of the assay and decrease the work required. Abstracts of this work have been reported previously (Greenspan, et al.z, 1954; Kriss and Greenspan, 1954). more...

Following prolonged administration of chloramphenicol, two cases of aplastic anemia, one of which ended fatally, were encountered. In a study to be reported elsewhere by one of us (M. S. H.), on the effects of chloramphenicol in the bacteriostatic control of chronic bronchopulmonary suppuration, 62 patients, ranging in age from 1 year to 72 years, were given the drug over periods of from 1 month to 14 months. Dosages of 1 gm., two to three times weekly and, in a few instances, daily, were administered after an initial period of more intensive antibiotic therapy, which included penicillin and/ or streptomycin. Thus, in a controlled series, 2 of 62 patients receiving the drug for long periods had severe hematological complications. In the two cases of aplastic anemia to be reported, the first of which ended fatally, the drug was given for approximately seven months and five and one-half months, respectively. REPORT more...

This large and useful book is the latest in aScientific Foundationsseries dealing with various topics in medicine. It contains 73 chapters, each well circumscribed and directed at a highly specific topic. Most of the nearly 100 authors are well known and the quality of the writing is quite high. The editors are to be congratulated on their choice of collaborators. The 73 chapters are arranged into major sections, most of which deal with clinical topics. The arrangement requires that each chapter be independent of the others, so that each can be read without reference to other parts of the book. Part of the usefulness of the book is that each small segment can be read and understood on its own. The book does not make a great effort to cover every area of cardiology completely; the authors seen to have had the freedom to write on topics of more...

Since the acquired immunodeficiency syndrome (AIDS) epidemic is partly a social phenomenon changes in the social behaviors that spread the disease are as necessary as the development of vaccines and other therapies. To help in the design implementation and evaluation of programs to curb the spread of AIDS there is a need for greater understanding of the human behaviors that transmit human immunodeficiency virus (HIV) infection as well as the social contexts in which these behaviors occur. Toward this end the US Committee on AIDS Research and the Behavioral Social and Statistical Sciences was asked to: 1) describe what is known about the spread of HIV and AIDS in the US with special attention to the quality of information at hand and the kind of additional information that is needed; 2) identify critical populations and indicate objectives and tasks related to them; 3) describe existing research findings in the behavioral and social sciences that should be useful in planning and choosing among interventions designed to control the spread of HIV infection; 4) describe existing research on interventions intended to facilitate behavior changes and ways to evaluate their effectiveness; and 5) identify new research that should be undertaken in these areas. The 7 chapters of the resultant report are divided into 3 parts: Understanding the Spread of HIV Infection; Intervening to Limit the Spread of HIV Infection; and Impediments to Research and Intervention. Also included are 6 background papers. Among the recommendations of the Committee are: vigorous programs of basic social and behavioral research on human sexual behavior; availability of condoms and treatment for sexually transmitted diseases through local public health authorities; drug treatment upon request for intravenous drug users; trials of sterile needle programs; and anonymous HIV antibody testing with appropriate counseling on a voluntary basis. more...

The article by Luft and Hunt 1 in this issue ofThe Journalhas acquired an urgent relevancy since it was accepted for publication. In that time interval, the Department of Health and Human Services has begun to release individually identified hospital death rates. Luft and Hunt examined the 1982 experience of patients undergoing cardiac catheterization in the 151 member hospitals of the Commission on Professional and Hospital Activities known to have had cardiac catheterization laboratories in that year. Confidentiality mechanisms ensured that the authors were blind to the identity of the hospitals from which the data came. The age of the patient and the patient's disease are both powerful influences on the probability of death, so the investigators sorted the patients into 12 categories, defined as the possible combinations of three age groups and four diagnostic groups. For each of these 12 categories, the whole-study death rate (across the more...

• A 76-year-old woman with rapidly progressive arthritis associated with a rising rheumatoid factor, acute joint effusion, and fever had remission of her symptoms and return of her laboratory values to normal following removal of a colonic carcinoma. ( Arch Intern Med 140:698-700, 1980) more...