Effectiveness of Reinduction and/or Dose Escalation of Ustekinumab in Crohn’s Disease: A Systematic Review and Meta-analysis

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Arrhythmogenic properties of disordered breathing during sleep in patients with cardiovascular disorders

The purpose of this study was twofold: to establish an ECG respiration monitoring system, and to evaluate the clinical usefulness of this system. Our purpose was to determine how many patients with cardiovascular disorders may have unrecognized sleep apnea and whether such apneic episodes are an important cause of cardiac arrhythmias. The study group included 81 patients, age range 40-95 years, and 13 healthy males, age range 52-72 years. The 24-h ECG respiration recordings were obtained with the two-channel holter recorder. Airflow at the nose using a nasal thermister or chest wall movement by impedance pneumography was recorded as respiration record on the second channel. Sleep apnea was observed 69% and 77-100% in the control subjects and patients with cardiovascular disorders, respectively. Episodes of sleep apnea were most frequent in the patients with old myocardial infarction. Grading of apneas was defined according to the length of apnea. Short duration apneas were observed only in the control subjects, but longer apneic episodes were observed in patients with cardiovascular disorders. Bradyarrhythmias observed were to be relative to apneic episodes longer than 20 s, while ventricular arrhythmias were observed only in the patients with old myocardial infarction, coincident with apneas lasting longer than 40 s. Atrioventricular conduction disturbances were also observed to be related to the occurrence of sleep apnea. These results suggest that 24-h ECG respiration monitoring is useful not only for the observation of sleep apneic episodes, but also in clarifying the relationship between cardiac arrhythmias and apneic episodes.     

Abnormal left ventricular response to isometric exercise in pure, isolated aortic regurgitation: beneficial effects of nifedipine

To examine the effects of nifedipine on the left ventricular (LV) functional response to isometric exercise in patients with aortic regurgitation (AR), 20 patients with isolated, moderate to severe AR performed 3 minutes of handgrip exercise at 33% of their maximal voluntary contraction, before and after administration of 20 mg of sublingual nifedipine. Although handgrip exercise produced similar increases in heart rate and systolic blood pressure before and after nifedipine treatment, heart rate was higher and systolic blood pressure lower with handgrip exercise during nifedipine treatment. LV end-diastolic volume index was not different during the control period and nifedipine handgrip exercise, but the increase in end-systolic volume index was smaller and the ejection fraction was higher during nifedipine handgrip exercise. Nifedipine reduces afterload and ameliorates handgrip exercise-induced LV dysfunction in patients with AR.     

Noninvasive detection of multivessel disease after myocardial infarction by exercise radionuclide ventriculography

The ability of exercise radionuclide ventriculography to detect multivessel coronary artery disease in patients who survived a single myocardial infarction was assessed. Seventy-four patients who had had myocardial infarction at least 8 weeks earlier underwent cardiac catheterization and exercise radionuclide ventriculography. Thirty-eight patients had had an inferior infarction: 25 with multivessel disease and 13 with single vessel disease of the right coronary artery. Thirty-six patients had had an anterior infarction: 26 with multivessel disease and 10 with single vessel disease of the left anterior descending coronary artery.

Among patients with anterior infarction there was no significant difference between patients with single vessel disease and patients with multivessel disease with regard to resting ejection fraction, exercise ejection fraction, and the mean change from rest to exercise. Patients with single vessel disease had a decrease in ejection fraction from rest to exercise of 2.2 ± 2.7% units (mean) ± standard error [SE]), compared with a decrease of 5.4 ±1.3% units in those with multivessel disease (p = not significant [NS]). Seventeen of 26 (65%) patients with multivessel disease and 6 of 10 (60%) with single vessel disease had a decrease in ejection fraction of at least 5 percentage units (p = NS).

In patients with inferior infarction there was no difference in the mean resting ejection fraction in those with single vessel disease (53 ± 2%) compared with those with multivessel disease (50 ±2%); however, the mean exercise ejection fraction in patients with single vessel disease (57 ± 3%) was significantly higher (p < 0.005) than that in patients with multivessel disease (45 ± 2%). Sixteen of the 25 patients with multivessel disease (64%) but only 1 patient with single vessel disease (7.7%) had a decrease in ejection fraction of at least 5 percentage units (p < 0.001).

A new wall motion abnormality developed in 8 patients with anterior infarction and 11 with inferior infarction with multivessel disease and none with single vessel disease. The sensitivity and specificity in predicting multivessel disease using the criteria of the development of a new wall motion abnormality or a decrease in ejection fraction with exercise of at least 5 percentage units were 80 and 92% for the patients with inferior infarction, but only 69 and 40% for the patients with anterior infarction.

These results suggest that exercise radionuclide angiography can be used to discriminate between single and multivessel disease after inferior myocardial infarction. For patients with anterior infarction, only a new abnormality in wall motion accurately predicts multivessel disease, but this occurred in only one third of such patients.     

Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects differing in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. Lipoprotein particles resembling the serum very low, intermediate, low, and high density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) in density, particle size, and morphology were isolated from the urine. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. However, little sieving effect was seen within the urinary HDL, which comprised a broad spectrum of particle sizes including the larger HDL₂, whose average diameter was similar to that of the plasma HDL. A sieving effect was not seen in the urinary LDL, except for a greatly increased proportion, about 20% of total particles, of HDL-like species. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10⁴ and 5 × 10⁴ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotein fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The fragments were derived in part from apo AI, the least acidic form of which was lost preferentially. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis. Apparently, the surface-exposed, readily exchangeable apolipoproteins are subject to proteolytic degradation upon glomerular filtration.     

Pulsed Doppler echocardiography in the diagnosis and estimation of severity of aortic insufficiency

Detection and estimation of the degree of chronic aortic insufficiency with pulsed Doppler echocardiography was attempted in 27 patients documented to have aortic insufficiency on aortography. Twenty-five patients had associated aortic stenosis or mitral valve disease, or both. A disturbed diastolic flow within the left ventricular outflow tract was recorded in all but one patient (Doppler sensitivity 96 percent). Aortic insufficiency was clinically undetected In three patients (clinical sensitivity 89 percent). In a small number of patients Doppler echocardiography also appeared to be highly specific for this disorder. The Doppler technique estimated the degree of aortic Insufficiency by assessing the distribution of diastolic flow within the outflow tract and the body of the left ventricle. A significant correlation between the Doppler method and the angiographic estimation of aortic insufficiency was found (r = 0.88, p < 0.01).     

Surgical repair of congenitally corrected transposition of the great arteries: Results and follow-up

Eighteen patients with congenitally corrected transposition of the great arteries had open heart repair for intracardiac associated defects. Fourteen patients (78%) are alive during the follow-up period (mean 4.5 years). Seventeen (94%) of the 18 patients had ventricular septal defect closure, and 12 (66%) insertion of a pulmonary artery conduit. Surgical repair of the tricuspid valve was required in 6 patients (33%) during the first operation and in 3 additional patients during a second operation (total 50%). When hemodynamic overload or cardiac compromise was detected after surgery it was directly related to identifiable residual defects such as atrioventricular valvular insufficiency, residual ventricular septal defect, or pulmonary conduit stenosis. Repeat open heart operation for residual defects was common during the follow-up period (8 of 18 patients, 44%). No patient showed primary systemic or pulmonary ventricular dysfunction during the follow-up period. None of the last 11 patients developed complete heart block. Postoperative intraventricular conduction defects were common and are presumably caused by surgical injury of the bundle branches.Our observations suggest that surgical repair of congenitally corrected transposition of the great arteries can be currently achieved with acceptable risk. Improved knowledge of the precise location of the specialized conduction system resulted in a marked decrease in the Incidence of atrioventricular (A-V) block in patients with congenitally corrected transposition of the great arteries undergoing intracardiac repair. In the absence of postoperative residual defects it can be expected that longevity and quality of life will improve considerably, but many of these patients may require a repeat operation.     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such, serum thyroglobulin determinations on and off thyroid hormone (T₄) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (< 1 ng/ml). Values during T₄ therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T₄ withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T₄. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T₄ therapy or less than 10 ng/ml off T₄ therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Tocainide therapy for treatment of ventricular arrhythmias: assessment with ambulatory electrocardiographic monitoring and treadmill exercise

Tocainide has shown promise in the acute suppression of ventricular arrhythmias and in the treatment of such arrhythmias considered refractory to other drugs. However, there is little experience with tocainide therapy using currently acceptable statistical end points in patients not receiving conventional antiarrhythmic drugs concurrently. Accordingly, a double-blind, crossover study design was used to compare the effects of 2 week periods of placebo therapy and small dose (400 mg every 8 hours) tocainide therapy in 10 patients with ventricular arrhythmias who were not receiving quinidlne, procainamide or disopyramide. Ventricular arrhythmias were assessed with 24 hour ambulatory electrocardiographic monitoring and treadmill exercise. Individual patients not responding to small dose tocainide with at least an 80 percent decrease in ventricular premature complexes on ambulatory monitoring were given doses of 600 mg and then 800 mg every 8 hours. Small dose tocainide therapy resulted in a decrease in ventricular premature complexes/hour from 364 ± 98 (standard error) to 127 ± 50 (p < 0.05) and 5 of 10 patients had at least an 80 percent decrease. At higher dose levels, two additional patients had at least an 80 percent decrease. The response of ventricular arrhythmias during treadmill exercise was comparable with that during ambulatory monitoring. Side effects were minor or nonexistent in the seven patients who responded to tocainide, and effective mean serum concentrations were 4.4 ± 1.9 μg/ml, a value significantly lower than that previously reported to suppress refractory ventricular arrhythmias. It is concluded that tocainide is an effective agent in patients not receiving concurrent therapy with conventional agents and that patients selected because of refractory ventricular arrhythmias may require higher serum concentrations of the drug than unselected patients.