The calcemic and phosphaturic effects of parathyroid hormone in the normal and uremic dog

The responsiveness of bone and kidney to highly purified bovine PTH was evaluated in normal (N) and uremic dogs. One group of uremic dogs (uremic-constant solute intake; U-CSI), maintained on a diet containing 1500 mg of phosphorus (P) daily developed the adaptive increases in phosphate excretion (FE_PO4) and PTH levels characteristic of uremia. A second group of uremic dogs (uremic-proportional reduction of solute; U-PRS), in which dietary P intake was reduced in proportion to the reduction in GFR, exhibited normal FE_PO4 and PTH values. During PTH infusion tubular reabsorption of phosphate per nephron mass decreased 2.5 mg/100 ml in U-PRS but only 1.4 in U-CSI (p < .001) and 1.1 in N (p < .001). After PTH the calcemic response was significantly and equally decreased in both U-CSI and U-PRS compared to N. In conclusion, the blunted calcemic response to PTH in uremia does not appear to be the only or predominant factor in the pathogenesis of hyperparathyroidism since the uremic dog treated with proportional reduction of phosphorus intake, which maintains a normal PTH level, also demonstrates this abnormality. The PTH-induced rise in phosphate excretion in the uremic nephron depends on the pre-existing degree of inhibition of renal tubular phosphate reabsorption. Finally, the uremic animals in which an adaptive phosphaturia was prevented (U-PRS) exhibited a magnified response in phosphate excretion per nephron to exogenous PTH infusion.     

Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: relation to serum lipoproteins.

Physically well-trained people generally have lower VLDL-triglyceride and higher HDL-cholesterol levels than sedentary subjects. To examine the underlying mechanisms of this lipoprotein pattern, we measured the lipoprotein lipase (LPL) activity in needle biopsy specimens of adipose tissue and skeletal muscle of competitive runners and of body weight-matched, physically less-active controls. The active sportsmen were either sprinters, whose training program consisted mainly of athletics of short duration or long distance runners undergoing a strenuous endurance exercise program. In sprinters (all males) the serum lipid and lipoprotein concentrations did not differ significantly from those of controls and the mean LPL activities in muscle and adipose tissue were also similar in these two groups. The long distance runners (both sexes), on the other hand, had higher means levels of HDL-cholesterol than the respective controls. The LPL-activity of both adipose tissue (p less than 0.05) and skeletal muscle (p less than 0.01) was significantly higher in male long distance runners than in control males. Female runners had higher muscle LPL activity than controls (p less than 0.01) but in adipose tissue the difference in LPL activity was not significant. Rough estimates calculated for LPL activity present in whole body adipose tissue and skeletal muscle indicated that total LPL activity was 2.3 times higher in male long distance runners and 1.5 times higher in female long distance runners than in the respective controls. In combined groups of male runners and controls, there was a highly significant positive correlation between the serum HDL-cholesterol level and the LPL activity of adipose tissue expressed per tissue weight (r = +0.72, p less than 0.001) or per whole body fat (r = +0.62, p less than 0.001). The group means of HDL-cholesterol and adipose tissue LPL activity in the five cohorts studied (male sprinters, distance runners and controls and female distance runners and controls) were also positively correlated (r = +0.94). It is concluded that endurance training is associated with an adaptive increase of LPL activity not only in skeletal muscle but also in adipose tissue. These changes are not observed in sprinters who are trained by exercises of shorter duration. The high HDL-cholesterol levels of physically well-trained people are probably accounted for, at least partly, by the increased LPL activity and the concomitant rapid turnover or triglyceride-rich lipoproteins.     

Trends in the Incidence of In-Hospital Mortality,Cardiogenic Shock,and Utilization of Mechanical Circulatory Support Devices in Myocarditis (Analysis of National Inpatient Sample Data, 2005–2014)

BackgroundMyocarditis may be associated with hemodynamic instability and portends a poor prognosis when associated with cardiogenic shock (CS). There are limited data available on the incidence of in-hospital mortality, CS, and utilization of mechanical circulatory support (MCS) devices in these patients.MethodsWe queried the 2005–2014 National Inpatient Sample databases to identify all patients aged >18 years with myocarditis in the United States.ResultsThe number of reported cases of myocarditis per 1 million gradually increased from 95 in 2005 to 144 in 2014 (Pfor trend <.01). The trend and incidence of endomyocardial biopsy remained the same despite the increase in clinical diagnosis. Overall, in-hospital mortality was 4.43% of total admissions without a change in overall trend over the study period. We also observed a significant increase in the incidence of CS from 6.94% in 2005 to 11.99% in 2014 (Pfor trend <.01). There was a parallel increase in the utilization of advanced MCS devices during the same time period such as extracorporeal membrane oxygenation or percutaneous cardiopulmonary support (0.32% in 2005 to 2.1% in 2014; P< .01) and percutaneous ventricular assist devices such as Impella/tandem heart (0.176% in 2005 to 1.75% in 2014; P< .01).ConclusionAlthough the incidence of myocarditis has increased in the last decade, the in-hospital mortality has remained the same despite increases in the incidence of CS, possibly reflecting the benefits of increased usage of advanced MCS devices. We noted that increasing age, presence of multiple comorbidities and CS were associated with an increase in in-patient mortality.     

Influence of elevated plasma free fatty acids on the glucagon response to hypoglycemia in normal and in pregnant women

We investigated the influence of an insulin-induced hypoglycemia on plasma glucagon in nonpregnant healthy young women and in women during the last month of gestation. Both groups were tested either in the basal state or during a period where free fatty acid plasma levels were increased by infusion of a lipid emulsion supplemented with heparin. Regular insulin was injected intravenously at the dose of 0.1 U/kg body wt in controls and 0.3 U/kg in pregnant women in order to obtain a similar lowering of blood glucose in all groups. In controls, the increase in plasma glucagon was maximum 30 and 45 min after insulin injection and averaged 130 pg/ml; the infusion of triglycerides and heparin which raised plasma FFA to about 1300 μEq/liter decreased basal plasma glucagon levels and reduced, by about 70%, the glucagon response to hypoglycemia. During the last month of pregnancy, the glucagon response to insulin-induced hypoglycemia was reduced by 60% (mean maximal increase 52 pg/ml); furthermore, raising plasma FFA to about 1500 μEq/liter completely abolished the glucagon rise induced by the insulin hypoglycemia. These results support the view that the glucagon release from A-cells can be modulated by the level of circulating plasma FFA.     

Multimodality Imaging of a Giant Right Coronary Artery Aneurysm

We describe a case of a 54-year-old woman who had a right cardiac mass found on coronary angiography. Echocardiography, computed tomography, and cardiac magnetic resonance imaging characterized it as a thrombosed giant right coronary artery aneurysm. This was confirmed on pathology. We present the role of multimodality cardiovascular imaging in the diagnosis and characterization of a giant coronary artery aneurysm.     

Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction: Report of two cases and review of the literature

The association of an autoimmune disease with a monoclonal immunoglobulin is not exceptional and most probably results from a dysfunction of the immunologic apparatus.This study describes two patients with monoclonal immunoglobulin A (IgA) and M (IgM) gammopathy, respectively, in whom pernicious anemia and finally gastric carcinoma developed. One patient had autoantibodies to gastric parietal cell and to thyroid microsomal antigen which could not be identified with the M-component. This observation, together with the fact that pernicious anemia occurred in one case before and in the other case after the discovery of M-component, suggests that different clones of cells were responsible for both disorders. Sixteen cases in which the patients had the same association have been collected from the literature and the data are compared with ours.     

Calcium channel blocking drugs for chronic, stable angina

The slow channel calcium blocking drugs have been shown to be efficacious in patients with chronic stable angina. They provide effective first alternative therapy to beta-blockers in preventing recurrent episodes of myocardial ischemia in patients who do not tolerate treatment with beta-blocking drugs because of, for example, pulmonary bronchospasm or hypoglycemia. The calcium blocking drugs often provide an additive effect in reducing anginal episodes when combined with beta-blocking agents and sometimes provide effective relief of chronic stable angina when beta-blocking drugs are unsuccessful. Diltiazem, nifedipine and verapamil are important additions to our therapeutic armentarium for the treatment of exercise-induced angina pectoris.     

Correlation between altered acetate utilization and hyperphagia in rats with ventromedial hypothalamic lesions

Incorporation of a tracer dose of acetate-1-¹⁴C given by intraperitoneal injection into normal and VMH-lesioned rats 2 days after surgery has been studied in vivo. To exclude adaptive metabolic effects due to meal-feeding and hyperphagia, the food intake of the lesioned animals was kept close to normal by using an automated food dispenser. The results show decreased recovery of ¹⁴C activity as ¹⁴CO₂ in the lesioned rats as compared to untreated animals during the first 4 hr after the injection, whereas the ¹⁴C incorporation into body lipids was significantly increased in the lesioned animals. The change in acetate utilization is shown to develop gradually during the first 2–3 days postoperatively. Moreover, the individual retention of ¹⁴C activity from acetate-1-¹⁴C is correlated to the subsequent gain in body weight during 8 days of ad-lib. feeding. In conclusion, the results clearly demonstrate an altered metabolism in the VMH-lesioned rat, so as to promote accumulation of body fat, even when hyperphagia is prevented. Furthermore, the concept “regulatory obesity” is reexamined in view of the findings presented.     

High-density lipoproteins: Epidemiologic profile and risks of coronary artery disease

The lipid-atherogenesis connection has undergone an evolutionary metamorphosis from a focus initially on serum total cholesterol, subsequently on other lipids, then on the lipoproteins that transport them, and now on the distribution of cholesterol in the low-density lipoproteins (LDL), high-density lipoproteins (HDL) and very low density lipoproteins. it is now established that the relation of serum total cholesterol to coronary heart disease (CHD) derives chiefly from the atherogenic LDL component, and that level of HDL cholesterol is inversely related to risk. The protective effect of HDL is at least as strong as the atherogenic effect of LDL and is independent of lipids and other risk factors. Every change of 10 mg/dl in the HDL cholesterol level is associated with a 50 % change in risk. At any level of serum total cholesterol, risk varies widely, depending on the $\text{LDL}\text{HDL}$ ratio. A serum total $\text{cholesterol}\text{HDL}$ ratio of 5.0 is associated with average risk; optimal ratios, around 3.5, correspond to half the standard risk. Further refinements in the lipid profile may be possible because there are several HDL and LDL subfractions with different atherogenic potential probably related to their apoprotein makeup. Only weak and inconsistent relationships of stroke and peripheral arterial disease to serum cholesterol and its lipoprotein fractions have been found, although there is the expected inverse relation to HDL cholesterol. An inverse relation of LDL level to stroke in women, and in men a possible excess mortality at very low serum cholesterol values attributed to colon cancer, have been reported.     

Clinical,electrocardiographic and follow-up observations in patients having ventricular fibrillation during holter monitoring: Role of quinidine therapy

Ventricular fibrillation occurred during Holter electrocardiographic monitoring in 5 of 3,307 consecutive patients. All five patients had Holter studies for evaluation of antiarrhythmic drug therapy; their ages ranged from 51 to 65 years. No patient had acute myocardlal infarction; all had congestive heart failure and severe left ventricular dysfunction. One patient had ischemic and four had nonischemic cardiomyopathy. All patients had recently begun treatment with oral quinidine and had plasma quinidine levels of 1.24 to 5.18 μg/ml. The Holter monitoring revealed that all had a long Q-T interval and that ventricular fibrillation began during frequent ventricular premature beats and was immediately preceded by ventricular tachycardia of the torsade de pointes type. The coupling interval of the ventricular premature beats initiating torsade de pointes was late (440 to 720 ms) and followed long preceding cycles (840 to 1920 ms). Ventricular fibrillation resolved spontaneously in two patients, but two of the remaining three patients died despite attempted cardiopulmonary resuscitation.It is concluded that (1) left ventricular dysfunction, chronic ventricular arrhythmias and initiation of quinidine therapy were the common findings in these patients; (2) a long Q-T interval, late coupled ventricular premature beats and long preceding cycles facilitate initiation of ventricular fibrillation in quinidine-treated patients; and (3) direct on-line monitoring should be utilized in the management of these patients.     

Clinical decision-making with treadmill testing and thallium 201

Fifty patients were prospectively evaluated for myocardial ischemia utilizing treadmill testing and thallium-201 imaging. By coronary angiography, 43 had significant coronary stenosis and seven were normal. The sensitivity, specificity, accuracy and predictive value of treadmill testing alone (81 per cent, 71 per cent, 80 per cent and 95 per cent) did not statistically differ from that of thallium-201 imaging (70 per cent, 86 per cent, 72 per cent and 97 per cent). Combined treadmill testing and thallium-201 imaging (84 per cent, 71 per cent, 80 per cent and 95 per cent) did not significantly affect the results of treadmill testing alone. Thallium-201 imaging failed to identify a number of patients with high risk lesions. The high prevalence of disease, the presentation of typical angina, preselection bias, multiple lead monitoring and exclusion of patients with abnormalities on the resting electrocardiogram probably accounted for failure of thallium-201 imaging to improve the results obtained with treadmill testing. The use of thallium-201 imaging in certain subsets of patients (resting electrocardiographic abnormalities, nondiagnostic treadmill testing, atypical chest pain or asymptomatic patients with abnormalities on treadmill testing) may be of value. However, the use of thallium-201 imaging as a routine screening procedure for myocardial ischemia in patients with typical angina, without due consideration of the prevalence of the disease in the population, is not justified.     

The Relationship of Pleural and Pericardial Effusion With Pulmonary Hemodynamics in Patients With Pulmonary Hypertension

BackgroundThe relationship between the presence of pleural and pericardial effusion in reference to hemodynamic parameters remains unclear in ambulatory patients with pulmonary hypertension (PH).MethodsConsecutive patients who underwent right catheterization (RHC) for the evaluation of pulmonary hypertension were enrolled. Point-of- care ultrasound was performed prior to the RHC to determine the presence of pleural effusion and pericardial effusion. We conducted a cross-sectional study to determine the association between presence of pericardial and pleural effusion with pulmonary hemodynamic variables.ResultsTwenty-five (78.1%) of 32 patients had evidence of PH by RHC. Mean pulmonary artery pressure of the population was 40.6 mmHg, and 68% (17/25) had WHO group I PH. Six (24.0%) of 25 PH patients had pleural effusions identified, of which 4 out of 6 (66.7%) had a pulmonary artery wedge pressure >15 mmHg. Eleven (44.0%) of the 25 PH patients were also found to have pericardial effusions, and most of those patients 10/11(90.9%) had an elevated right atrial pressure >10 mmHg. The presence of a pleural effusion was associated with a pulmonary artery wedge pressure >15 mmHg (p = 0.032) and the presence of a pericardial effusion was associated with a right atrial pressure >10 mmHg (p = 0.004). Detection of pleural effusion had a poor positive predictive value (67%) for the presence of pulmonary venous hypertension, whereas presence of a pericardial effusion was highly predictive (89%) of the presence of systemic venous hypertension.ConclusionsSystemic venous hypertension was associated with the presence of pericardial effusions, while pulmonary venous hypertension is associated with pleural effusion development in ambulatory patients with pulmonary hypertension.     

Preliminary report: the effects of acute acidosis on alanine and glucose metabolism across the liver, gut, kidney, and muscle in the dog

Acute metabolic acidosis (AMA) in the dog results in a 48% increase in arterial alanine concentration and an 11% fall in blood glucose. Extraction/production of glucose and alanine were studied by A/V sampling and electromagnetic blood flow probe measurements. Alanine and total amino-N release by muscle increased in acidosis Hepatic glucose release was reduced. More marked changes in metabolism occur in AMA in the dog than previously considered.     

Effects on ventricular function of disopyramide,procainamide and quinidine as determined by radionuclide angiography

To evaluate the effects of the 3 commonly used antiarrhythmic agents—disopyramide, procainamide and quinidine—on left ventricular (LV) function, these 3 agents were administered in random sequence after control radionuclide angiography performed at rest and during exercise in 17 patients. Drug dosages were tailored to achieve therapeutic blood levels 5 minutes before and 2 to 3 hours after drug administration. The mean dose of disopyramide was 141 ± 26 mg every 6 hours, procainamide, 441 ± 100 mg every 4 hours, and quinidine, 401 ± 101 mg of the gluconate preparation every 6 hours. The patients received the appropriate dosage for 7 or more days before repeat radionuclide angiography was performed. The ejection fraction at rest was: control 60 ± 13%, disopyramide 55 ± 11%, procainamide 58 ± 11%, and quinidine 59 ± 12%. The exercise ejection fraction was: control 61 ± 14%, disopyramide 58 ±13%, procainamide 58 ±12% and quinidine 61 ± 13%. In neither case, at rest nor during exercise was there any significant difference observed between any of the agents or between any individual agent and control. However, at rest 8 subjects had a 5% or more decrease from the control value with disopyramide, 5 had a 5 % or more decrease with procainamide and 6 had a 5 % or more decrease with quinidine, whereas during exercise the decreases were 8, 6 and 5%, respectively. These values were not statistically different but suggest that caution should be taken in administering all 3 agents, particularly to patients with impaired LV function, because individual sensitivity to a given agent may precipitate a significant decline in LV function.     

10-year trends in the number of board-certified paediatricians and the ratio of paediatricians to children in China: an analysis of nationwide data

Background

In recent years, the shortage of paediatricians in China has led to delays in paediatric care and temporary shutdowns of paediatric clinics in many regional hospitals. Such phenomena and events have caused widespread anxiety in the public. The aim of this study is to examine the severity of the shortage of paediatricians. The findings may provide new insight for this health-care crisis.