Effects of pharmacologic hyperglucagonemia on plasma amino acid concentrations in normal and diabetic man

Four normal and five insulin dependent diabetic men received a 2 h pharmacologic glucagon infusion (50 ng/kg/min) resulting in plasma glucagon levels (4400 pg/ml) similar to those seen in glucagonoma patients. In normal subjects in whom plasma insulin concentrations rose significantly (239 uU/ml) and the blood level of 15 of the 18 amino acids measured fell significantly. In contrast, in the diabetic men who secreted no insulin in response to glucagon (no rise in C-peptide levels), only 10 of 18 amino acid levels fell significantly. The branched chain amino acids valine, leucine and isoleucine, as well as tyrosine and phenylalanine were among the 8 amino acids which showed no change in response to glucagon in the diabetics. Thus, glucagon appears to have no acute affect on branched chain amino acid levels in man.     

Cardiac hypertrophy: Useful adaptation or pathologic process?

An extensive body of evidence supports the concept that cardiac hypertrophy and normal cardiac growth develop in response to increased hemodynamic loading and abnormal systolic and diastolic stresses at the myocardial fiber level. The pattern of hypertrophy reflects the nature of the inciting stress. Experimental studies indicate that if the stress is moderate, gradually applied, and the animal young and healthy, physiologic hypertrophy of muscle with normal contractility develops. In this circumstance, cardiac hypertrophy may be regarded as a useful adaptation to increased hemodynamic loading. When the inciting stress is severe, abruptly applied, or the animal old or debilitated, pathologic hypertrophy develops: in this circumstance, the cardiac muscle produced is abnormal and exhibits depressed contractility. Of particular clinical relevance is the intermediate situation which seems to develop in many patients with chronic left ventricular pressure-overload and perhaps also in left ventricular volume-overload. In this situation, chronic left ventricular pressure or volume overload is initially matched by adequate hypertrophy in the appropriate pattern. Eventually, in some patients, hypertrophy fails to keep pace with the hemodynamic overload so that a systolic stress imbalance occurs at the myocardial fiber level and left ventricular pump failure ensues. If this situation persists uncorrected, it is possible that the increasingly high wall stresses will convert physiologic to pathologic hypertrophy. The task of the clinician is to identify this intermediate stage and to correct the abnormal hemodynamic loading before the transition to pathologic hypertrophy becomes complete.     

Changes in arrhythmogenic properties and five‐year prognosis after carbon‐ion radiotherapy in patients with mediastinum cancer

Introduction

Carbon‐ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon‐ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra‐cardiac cancer treated with carbon‐ion radiotherapy that included irradiating the heart.

Methods and Results

In April–December 2009, eight patients were prospectively enrolled (including two male, aged 72.5 ± 13.0 years). They were treated with 44–72 Gray equivalent (GyE), with their hearts exposed to 1.3–19.1 GyE. High‐resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre‐existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five‐year follow‐up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events.

Conclusion

Although this preliminary study has several limitations, carbon‐ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

     

Accurate estimates of absolute left ventricular volumes from equilibrium radionuclide angiographic count data using a simple geometric attenuation correction

To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d degree) and at a distance (d') from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates. Using blood sample counts obtained at d degree or d', the attentuation-corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 +/- 100 [+/- 1 standard deviation] and 185 +/- 102 ml, p less than 0.001) were smaller than the average cineangiographic end-diastolic volume (217 +/- 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 +/- 104 and 220 +/- 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d degree or d', the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d degree, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 +/- 98 ml, p less than 0.05) was less than the average cineangiographic end-systolic volume (128 +/- 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume. Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator.     

Effect of a twelve-hour hiatus in propranolol therapy on exercise tolerance in patients with angina pectoris

To determine whether propranolol can be administered twice daily without any loss of antianginal effect, we studied nine men receiving long-term propranolol therapy for stable angina pectoris. Each patient performed bicycle exercise to the point of angina on two consecutive mornings. By means of double-blind placebo-propranolol administration before the test, the study created a situation whereby on one day the exercise took place 12 hours after the last dose of propranolol, and on the other day, $\text{1}\text{1}\text{2}\text{hours}$ after a dose. Despite markedly lower blood levels of propranolol on the day that exercise was performed 12 hours after the last dose, exercise time to angina was nearly identical on the 2 days. We conclude that long-term therapy with propranolol for angina pectoris can be administered on a twice daily basis with no loss of effectiveness.     

Acute dermatomyositis-polymyositis and malignancy

A partial review of selected published case reports of AD-P associated with malignancy has been enhanced by the presentation of pertinent data on 15 unreported examples of the association. It is noteworthy that the first case in current literature of AD-P associated with a malignancy was described in 1916. The brief clinical report of a patient with proximal muscle weakness and skin lesions, with the obvious association with a malignancy (adenocarcinoma of the stomach), describes an example that has been repeated many times with different types of tumors but with essentially no variations in the clinical findings.In 1959 Williams identified 590 cases of AD with an overall tumor rate of 15%,³¹ and recently Barnes identified 258 cases of AD associated with a malignancy.³³The original designation, dermatomyositis or AD, has now been expanded to include proximal muscle polymyositis with systemic involvement, which syndrome at the current state of the art is indistinguishable clinically and pathologically from AD except for the lack of skin lesions. It may be that at some future time one or more immunologic features may differentiate the clinical entity polymyositis from AD and further subdivide each of these entities from similar clinical syndromes associated with a malignancy. However, the problem in management in either AD or polymyositis is similar.¹A number of patients with a malignancy and muscle weakness or neuropathy have been reported. These associations have been mentioned briefly, but insufficient data are available to determine whether these should be considered as a variant of AD-P or only casually related conditions with certain clinical features in common.Most of the patients described in the literature of AD-P with an associated malignancy have had skin lesions; a minority only have lacked this feature. However, unless a patient is followed carefully, it is possible for a transient or evanescent erythema or insignificant skin lesions to be present and not recorded in the case record.In the patients with malignancy and AD-P, there are no clinical features or laboratory findings unique to the malignancy in contrast to a carcinoma unassociated with AD-P, nor are the clinical features or laboratory findings of AD-P with malignancy different from those without a malignancy, except for one feature. The fatal determination, usually attributed to the malignancy, may be associated with a florid type of dermatomyositis, better described as rapidly progressive dermatomyositis, relentless muscle weakness, and failure of the respiratory and pharyngeal musculature.Approximately 15% of the patients with typical AD-P have an associated malignancy. Sometimes it precedes the symptoms of the collagen-vascular disease by one or more years. In other patients, the reverse is true by a similar period of time. In a few patients with AD-P, two related or chronologically unrelated tumors have appeared. Most reports favor a more than casual relationship, e.g., the recent study by Barnes.³³ Another recent survey casts doubt on this relationship.⁹⁷ We still lack epidemiologic information based upon statistically reliable data of cases with the combined condition, nor are there comprehensive data in this country of malignancy in patients without AD-P, in respect to decades of life, sex, and site and type of tumor.³⁴The cause either of AD-P or most malignancies is unknown. It is easy to speculate positively versus negatively as to whether or not two diseases might have had their initiating pathogenesis at the same time, with clinical symptoms or laboratory findings of one or the other predominating for weeks, months, even years. I tend to favor a concomitant pathogenesis associated with disproportionate development of clinical symptoms. At the moment a virus participating in the pathogenesis seems intriguing, but firm proof is lacking.Females tend to predominate because of the larger number of genital and breast tumors, which is not quite counterbalanced by tumors in lung and gastrointestinal tract, which are more common in the male.³³ In the newly reported cases presented in this review, the males exceeded the females by a ratio of 2:1, probably because a majority of the cases came from army or VA hospitals.The clinical appearance of a malignancy associated with AD-P, in adult life, usually comes after age 40 yr. A few examples of noninvasive tumor with AD-P in the prepuberty years have been reported. One girl age 10 yr had a chromophobe adenoma. The tumor probably was present when symptoms of AD appeared. In the second patient, a boy with hyperplasia of the adrenals, symptoms appeared at age 10 yr. Also, three examples of leukemia have been reported in children. Note should also be made of the combined appearance of AD-P and malignancy in a 17-yr-old male with reticuloendotheliosis. This is borderline between childhood and adulthood. One patient in the previously unreported cases had a probable Wilms tumor removed at age 17 yr and developed systemic symptoms of AD 7 yr later. However, not one of these observations negate the statement that AD-P with malignancy is an adult disease.The treatment of dermatomyositis in patients with an associated malignancy is the same as in those without a malignancy; the same holds for the tumor. Furthermore, one might expect that the combined use of corticosteroids and immunosuppressive drugs, useful in either AD-P or a malignancy, might have an enhanced beneficial effect. There are too few cases reported or observed unreported to make any statements in this category. One patient in my series, E.A., received large doses of corticosteroids and a course of methotrexate, but the course was inevitably regressive.Several of the clinical features frequently observed early in the course of AD-P without an associated malignancy were not reported in the cases in the literature nor seen in the series of new cases observed.¹ This concerns the incidence of arthralgias, sometimes called atypical RA, sclerodermatous changes either in the skin or subcutaneous calcinosis, or Raynaud phenomenon. The incidence of each of these three clinical findings may be assumed to be low in either the reported cases or in the cases described and previously unreported.     

Pulmonary hypertension in systemic lupus erythematosus: Report of four cases and review of the literature

Pulmonary hypertension has been reported rarely in patients with systemic lupus erythematosus (SLE). During the past 3$\text{1}\text{2}$ yr we have observed pulmonary hypertension as a major clinical manifestation of their disease in four of 43 patients with well-documented SLE followed at our institution.Pulmonary hypertension could be atrributed to underlying lung disease in three and was considered to be primary in the remaining patient. Neither hydralazine nor prednisone administration had any effect on the course of the pulmonary hypertension in these patients.The presence of pulmonary hypertension in the course of active SLE may be more common than previously recognized.     

Comparison of long-term clinical outcomes of external and internal pancreatic stents in pancreaticoduodenectomy: randomized controlled study

Background

To determine the most appropriate pancreatic drainage method, by investigating differences in 12-month clinical outcomes in patients implanted with external and internal pancreatic stents as an extension to a previous study on short-term outcome.

心房颤动患者心房肌钾电流的研究

目的:研究心房颤动患者心房肌内向整流钾电流和乙酰胆碱敏感钾电流的变化,探讨两种离子通道电流变化在心房颤动发生与维持中的作用。方法:应用膜片钳全细胞技术记录并比较19例风湿性心脏病心房颤动患者(心房颤动组)和18例风湿性心脏病窦性心律患者(窦性心律组)心房肌内向整流钾电流和乙酰胆碱敏感钾电流密度的大小。结果:在-60mV～-120mV时,与窦性心律组相比,心房颤动组内向整流钾电流密度绝对值增大,乙酰胆碱敏感钾电流密度绝对值降低。其中在-100mV时,内向整流钾电流密度从窦性心律组的(4.01±1.01)pA/pF(n=18)增大到心房颤动组的(8.94±1.26)pA/pF(n=19,P<0.001);乙酰胆碱敏感钾电流密度从窦性心律组的(24.57±0.77)pA/pF(n=18)降低为心房颤动组的(13.38±1.03)pA/pF(n=19,P<0.001)。结论:心房颤动时,内向整流钾电流密度绝对值增大,乙酰胆碱敏感钾电流密度绝对值降低,两种电流的改变可能与心房颤动的发生和维持有关。     

Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus

PH is an uncommon manifestation of SLE. The symptoms of PH develop within a few years after the onset of the multisystem disease. The most common presenting complaints of SLE patients with PH are dyspnea on exertion, chest pain, nonproductive cough, edema, and fatigue or weakness. The important physical findings are a loud second pulmonic heart sound and a right ventricular lift. The chest roentgenogram shows a cardiomegaly, a prominent pulmonary segment, and usually clear lung fields. Pulmonary function tests may show evidence of restrictive lung disease; however, the physiologic abnormalities are mild and out of proportion to the severity of the PH. The diagnosis of PH is established by cardiac catheterization showing elevated pulmonary artery pressure, normal capillary wedge pressure, and no evidence of intracardiac or extracardiac shunts. Pathologic examination of the lung demonstrates angiomatoid lesions involving muscular pulmonary arteries. There is a thickening of the media and subintima of the arterioles. Immunoglobulin and complement deposits are found in the walls of pulmonary arteries. Immunoglobulin eluted from the lung contains rheumatoid factor and antinuclear antibody including antibody to DNA activity. DNA antigen is also present in walls of blood vessels. These results suggest an immune complex deposition process as a mechanism in the pathogenesis of PH in SLE. The clinical course of PH in SLE is variable. Symptoms may be mild and the disease follows a stable and protracted course for several years. It can, however, develop a progressive course ending in death in a few years. The clinical response of SLE patients with PH to treatment with high doses of systemic corticosteroids is not consistent or predictable.