Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs

The role of brain catecholamines in the regulation of growth hormone secretion was investigated in pentobarbital-anesthetized dogs by using drugs which modify the function of adrenergic neurons and receptors. Intravenous administration of L-dopa produced a prompt, statistically significant increase in plasma growth hormone concentration. This response was not significantly reduced by blockade of peripheral dopa decarboxylase activity with carbidopa. Clonidine, an alpha-agonist which penetrates the brain, increased plasma growth hormone secretion. Norepinephrine, epinephrine, dopamine and isoproterenol, catecholamines which do not penetrate the blood-brain barrier, failed to affect plasma growth hormone concentration when administered intravenously. Apomorphine did not produce a statistically significant increase in plasma growth hormone concentration when administered directly into the the third ventricle, and pimozide failed to abolish the increase in plasma growth hormone produced by L-dopa. The increase in plasma growth hormone concentration produced by intravenous L-dopa and clonidine was prevented by administration of phentolamine or phenoxybenzamine directly into the third ventricle. The response to L-dopa was also abolished by intraventricular procaine. In dogs in which central beta-adrenergic blockade was produced by intraventricular L-propranolol, the growth hormone response to L-dopa was greater than it was in control dogs treated with intraventricular D-propranolol. The data indicate that in pentobarbital anesthetized dogs, the increase in growth hormone secretion produced by L-dopa is mediated by norepinephrine, rather than dopamine, that the site of action of the norepinephrine is central, above the median eminence and inside the 'blood-brain barrier', and that the norepinephrine acts via alpha-adrenergic receptors.     

Changes in spontaneous and evoked release of transmitter induced by the crotoxin complex and its component phospholipase A2 at the frog neuromuscular junction.

The time course and characteristics of the changes induced by the action of the crotoxin complex and of its component phospholipase A₂ on transmission at the frog neuromuscular junction was studiedin vitro at single endplates using intracellular recording techniques. Both the crotoxin complex and phospholipase A₂ induced variable changes in spontaneous transmitter release in which bursts of miniature endplate potentials alternated with periods when the frequency of miniature endplate potentials was stable but their amplitudes were markedly heterogeneous. The bursts of miniature endplate potentials were of sudden onset and of a high initial frequency, and their duration and incidence were highly variable both at one endplate and between endplates. These changes in the frequency and amplitude of miniature potentials occurred both before and after the abolition of neurally evoked endplate potentials and in the presence of tetrodotoxin. At a late stage in crotoxin intoxication, potassium depolarization of the motor nerve terminals failed to increase spontaneous transmitter release. Both the crotoxin complex and phospholipase A₂ reduced the amplitude of endplate potentials although phospholipase A₂ was less effective. The course of depression of the quantal content of evoked transmitter release induced by the crotoxin complex was occasionally interrupted by a brief facilitation of response; these irregularities in the rate of depression were more clearly seen when endplate potentials were recorded at partially curarized endplates exposed to either the crotoxin complex or to phospholipase A₂. At the stage of abolition of endplate potentials an increase in the external concentration of Ca^{2 +} enabled the evoked response to be restored temporarily. The crotoxin complex and phospholipase A₂ had no effect on the input resistance of the sarcolemmal membrane, but raised the threshold stimulus required to initiate an action potential at concentrations which affected transmitter release. Crotapotin did not affect any of the measured parameters even at high concentrations.The diversity of changes observed in the properties of spontaneous and evoked transmitter release, suggests that the crotoxin complex and phospholipase A₂ may induce two kinds of alterations in the structure of the presynaptic membrane as a result of the action of phospholipase A₂, viz (a) the formation of transient instabilities with an increased Ca^{2 +} inflow and (b) prolonged disturbance of the calcium channel and/or the synchronized release of subunits at the active zone.     

Pharmacogenomics and Opioid Use Disorder: Clinical Decision Support in an African American Cohort

Opioid use disorder (OUD) constitutes a significant public health burden as opioid overdose deaths have continued to rise in the United States. Although treatment modalities are available to manage OUD, some patients experience challenges achieving their OUD management goals. Some of these challenges may be attributable to inherited genetic variations, or polymorphisms, on the genes that code for proteins impacting the pharmacokinetics or pharmacodynamics of medications used in OUD management. Clinical pharmacogenomics testing can elucidate these polymorphisms; however, a lack of real-world evidence for the use of pharmacogenomics in OUD management complicates the implementation process. We conducted a retrospective cohort study of 113 patients undergoing buprenorphine-based OUD management in Northeast Washington D.C. to determine if clinical pharmacogenomics testing for CYP3A4 and CYP3A5 would impact treatment outcomes. Data were collected from the electronic medical record (EMR) from December 30, 2015 to December 31, 2016. Study outcomes were based on presence of withdrawal symptoms, instances of unauthorized substances in urine drug tests (UDTs), and sublingual buprenorphine/naloxone (SBN) dose with standard-of-care (SOC) dosing versus pharmacogenomics (PGx)-based dosing. Pearson correlation tests, Wilcoxon signed rank tests, Wilcoxon rank sum tests, and one-way ANOVA tests were used. Linear and logistic regression analyses were used to assess predictors of withdrawal symptomatology. Kaplan-Meier survival analyses were used to assess time to first withdrawal. Our research suggests that patients with at least one copy of the CYP3A4*1B allele exhibit an accelerated rate of metabolism compared to the wild-type allele CYP3A4*1.     

Skin testing in farmers' lung disease

Intradermal skin tests with a culture filtrate antigen of Micropolyspora faeni grown on a synthetic medium were performed on patients with farmers' lung disease (FLD) and well farmers with and without antibodies to a panel of FLD antigens. Seventy-five percent of the FLD patients, 79% of the well farmers with M. faeni antibody, and 5% of well farmers without M. faeni antibody had a 2+ or greater intradermal immediate skin-test reaction. Prausnitz-Küstner (P-K) reactions were positive using serum of M. faeni immediate skin test-positive FLD patients. IgG-rich fractions from a staphylococcal protein A-Sepharose column of such serum contained the sensitizing factor whereas IgG-depleted fractions did not. M. faeni—specific IgE could not be detected in serum by a polystyrene radioimmunoassay. Positive late-onset (6-hr) skin tests occurred only in FLD patients and farmers with precipitating antibody. Biopsy specimens of the 6-hr reactions revealed a generalized dermal and perivascular polymorphonuclear infiltrate with deposits of immunoglobulin and complement about blood vessels. The skin-sensitizing factor noted in FLD patients and well farmers with antibody is not disease specific. This factor appears to be associated with the IgG-rich fraction of serum, and its role in the pathogenesis of FLD is unclear.     

闭孔神经与阴部神经缝接治疗截瘫后的大小便失禁

在目前还无法使损伤的脊髓再生的情况下,我们在15具成人尸体上做了应用解剖学的的研究。试图用闭孔神经的分支改道修复阴部神经的主要功能支,以修复低位的脊髓损伤和尾神经损伤所致的大小便失禁。并初步过渡到临床,完成1例手术。     

缺氧,缺血及再灌注山羊血浆对血管内皮细胞和中性粒细胞的影响

为了探讨缺氧，缺血及再灌注损伤的发生的机制，我们分别观察了缺氧（模拟海拔４０００ｍ高原）２４ｈ山羊血浆（ＨＰ），缺血１ｈ（在上述条件下于缺氧２４ｈ末放血使血压维持在６．０ｋＰａ１ｈ）山羊血浆（ＩＰ）和再灌注回输放出血液后２４ｈ）山羊血浆（ＲＰ）对中性粒细胞（ＰＭＮ）及培养的肺动脉内皮细胞（ＰＡＥＣ）的作用，ＰＭＮ在分别含ＨＰ、ＩＰ和ＲＰ的培养中温育１ｈ末，细胞活力明显升高（Ｐ〈０．００１），其升高     

Activation of the complement sequence by extracts of bacteria and fungi associated with hypersensitivity pneumonitis.

Complement (C) consumption by antigens associated with hypersensitivity pneumonitis was investigated. Micropolyspora faeni in the presence of precipitating antibodies consumed C in a manner similar to the BSA-anti BSA system. An extract of M. faeni was shown to consume C and convert C3PA to C3A in the absence of detectable antibodies. In addition, three species of Aspergillus and two strains of Thermoactinomyces vulgaris were also shown to have the same activity with respect to C3PA. Mucor racemosus, Hormodendrum sp. and a mixed extract of Penicillium did not convert C3PA.     

A simple method for keeping allergenic extracts at a temperature near 4 °C during in-office use for skin testing and immunotherapy

A method is needed for keeping ragweed pollen aqueous allergenic extracts at a temperature near 4 °C while they are in use for skin testing and immunotherapy in order to prevent deterioration in potency from warming. A polystyrene foam icebox is described which can be cooled with sacks of coolant which have been reduced to a temperature of ?17 °C in the freezing compartment of a standard refrigerator. Both icebox and coolant can be readily obtained from standard commerical sources and are inexpensive. When sufficient adequately cooled coolant is properly employed, this icebox will maintain the temperatures of allergenic extracts in the desirable range of 2 ° to 4 °C while they are in use for skin testing and immunotherapy.     

The effects of isoproterenol Mistometer, with recommended use

Isoproterenol as an effective bronchodilator drug has achieved widespread clinical use. In recent years there have been reports of deleterious side effects of this drug with regard to changes in arterial blood gases, cardiovascular effects, and possible unexpected mortality. However, prior reports have not considered the effects of this drug when the dosage and mode of administration are the same as in the clinical situation. This study indicates that the administration of isoproterenol in a standard commercially available device by the method advised for clinical use does result in effective bronchodilation with a mean maximal increase in FEV₁ of 43 per cent and of FVC of 32 per cent as compared to baseline values. Electrocardiographic changes and arrhythmias were not observed. Nor did clinically significant changes in heart rate or blood pressure occur. No statistically significant changes were observed in pH, arterial carbon dioxide tension (PaCO₂), or arterial oxygen tension (PaO₂) during the study. However, analysis of the data with regard to each individual subject did demonstrate a decrease in PaO₂ of possible clinical significance in one of the 10 subjects. This study would suggest that the effects of isoproterenol Mistometer with recommended use provide bronchodilator action without significant subjective or objective negative side effects in the patient with acute asthma.     

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE at 0.1 μg/ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance (“optimal dose”) for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 μg of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 of the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.     

Computer methods for analysing the high-frequency electrocardiogram

The high-frequency electrocardiogram (e.c.g.) is similar to the clinical e.c.g. commonly interpreted by clinicians except that a wider recording bandwidth is used. This extended signal bandwidth permits more information about the cardiac electrical activity to be perceived than can be seen in a clinical e.c.g. The high-frequency data appear as waveform features called notches and slurs. The notches have been correlated with coronary heart disease by several investigators. Most of the work in high-frequency electrocardiography has been done by manual techniques with minimal automation of the signal analysis. The purpose of this project was to develop computer algorithms for the automatic recognition and characterisation of notch parameters. Investigations in this study were conducted in both the time and frequency domains using digital filtering and fast Fourier transform techniques. Methods for notch recognition and quantification by computers were evaluated.     

Presidential address. The advancement of the knowledge and practice of allergy.

State and local allergy societies have appeared in response to pressures created by progressive specialization, increase in knowledge, and need for cost control within the field of allergy and clinical immunology. They provide a mechanism whereby allergists and immunologists with many different interests and functions can work in an integrated and cooperative manner to provide, in a cost-effective fashion, adequate patient care, teaching, and research in allergy and immunology for the geographic area. Maximum effectiveness requires close liaison with medical schools, state medical societies, national allergy organizations, and the local chapter of the Asthma and Allergy Foundation of America. Their structure should permit frequent close communication between members in various fields of allergy and clinical immunology, and the organization of committees that can accomplish the hard work of ensuring care for the disadvantaged patient, time and money for research, cost control, identification and rehabilitation of the poorly functioning allergists, continuing education for physician and patient, and all of the other tasks that make the practice of allergy and clinical immunology such a wonderful and absorbing way of life.