Short-term effects of 1,25-dihydroxycholecalciferol on disordered calcium metabolism of renal failure

The short-term effects of 1,25-dihydroxycholecalciferol (1,25-(OH)₂D₃) on disordered calcium metabolism were studied in 15 trials in patients with advanced renal failure and, for comparison, in 20 trials in normal persons. The steroid was given orally in doses of 0.027, 0.14, 0.68 and 2.7 μg/day for 7 to 15 days. Calcium absorption and urinary calcium increased after the administration of 0.14 to 2.7 μg/day in normal subjects, but 0.68 to 2.7 μg/day was needed to augment calcium absorption in the patients with uremia. Fecal calcium decreased significantly during metabolic balance studies. Serum calcium increased markedly only in the patients with uremia, and hypercalcemia occurred at a dosage level of 2.7 μg/day. With the increase in serum calcium, the blood levels of immunoreactive parathyroid hormone (iPTH) decreased. Urinary calcium increased substantially only in normal subjects. The steroid corrected the “vitamin D resistance” of uremia, suggesting that the renal production of 1,25-(OH)₂D₃ in uremia is defective.     

Studies on renal function after relief of complete unilateral ureteral obstruction of three months' duration in man

Individual renal functions were studied in a 24 year old woman following relief of a complete unilateral ureteral obstruction of three months' duration. Function of the previously obstructed kidney was investigated over a period of six weeks and compared with that of the contralateral unobstructed kidney. Within one week after relief of obstruction, the creatinine clearance in the affected kidney increased from 2.6 to 10.2 ml/minute and remained essentially unchanged thereafter. In comparison to the contralateral kidney, fractional sodium excretion was moderately increased, maximal diluting ability was normal, generation of free water (corrected for glomerular filtration rate) was supranormal, and urinary excretion of phosphate was very low; the latter was presumably due to excessive tubular reabsorption of phosphate. The urinary pH was higher than that from the contralateral kidney and did not decrease normally after the ingestion of ammonium chloride. The excretion of titratable acid was low, partially due to low urinary phosphate excretion and high urinary pH. After 16 hours of water deprivation, the urine from the affected kidney remained hypotonic to the plasma. The natriuretic response to volume expansion, sodium retention after the administration of mineralocorticoids and the phosphaturic action of parathyroid hormone extract were normal as compared to the contralateral kidney. Despite the prolonged period of complete ureteral obstruction, the renal function attained by this kidney would probably have been adequate to support life were this kidney the only one available to the patient.     

Streptococcal lymphadenitis in homosexual men with chronic lymphadenopathy

Lymphadenopathy is an important clinical problem in homosexual men. Over a period of 10 months, three homosexual patients were treated for chronic lymphadenopathy and spontaneous lymphadenitis of the inguinal lymph nodes. All patients presented with fever, chills, and rapidly enlarging inguinal masses. In each case, cultures showed group A beta-hemolytic streptococci. None of the patients had an obvious portal of entry for infection, and all had responses to penicillin and surgical drainage. Streptococcal lymphadenitis should be considered in any homosexual man with chronic lymphadenopathy in whom rapidly enlarging inguinal nodes develop.     

Septic shock in a young splenectomized man

For convenience, clinical findings are often artificially forced into finite pigeonholes such as “positive” or “negative.” This convention obscures much of the inherent uncertainty in diagnosis and can result in serious misinterpretation of the significance of certain observations. Unhappy past experience with the poor predictive accuracy of electrocardiographic stress testing in asymptomatic patients is one such example. As an aid to understanding the limitations of clinical diagnosis, an epistemologic model of judgment was developed. According to this model, judgments are viewed as existing on three separate dimensional levels, each of which is rigorously defined and unambiguously quantified. The first dimension expresses diagnostic belief in terms of a numeric probability; the second quantifies the degree of confidence in the probability estimate; and the third defines the information that derives from the probability and confidence. The practical clinical relevance of this conceptual model is illustrated by applying it to a common clinical problem: the interpretation of a “positive” electrocardiographic stress test result in an asymptomatic man. This process—termed herein “metadiagnosis”—provides a new perspective by which the art of diagnosis might be made more accurate and explicit.     

Hypocalcemia in magnesium-depleted dogs: evidence for reduced responsiveness to parathyroid hormone and relative failure of parathyroid gland function

The effect of magnesium depletion on serum calcium and magnesium and on the response to the infusion of parathyroid extract (PTE) was evaluated in nine adult mongrel dogs during a control period, magnesium depletion, and following magnesium repletion. Magnesium depletion was associated with a fall in serum magnesium and calcium, and both returned to normal with magnesium repletion. There was a significant direct correlation between the serum concentration of calcium and magnesium in the magnesium-deficient state. During magnesium depletion, there were significant calcemic and phosphaturic responses to PTE, but these effects were reduced; the impaired responsiveness of the skeleton and the kidney to PTE returned to normal after magnesium repletion. Serum levels of immunoreactive parathyroid hormone, measured in two animals during the control and magnesium depletion state, remained stable during magnesium depletion, despite the hypocalcemia present. These results indicate that both impaired responsiveness of the skeleton to parathyroid hormone and reduced secretion of the hormone in response to hypocalcemia exist in dogs with magnesium depletion. Each of these factors probably contributes to a reduced level of serum calcium in magnesium depletion, and they may compound each other and hence aggravate the degree of hypocalcemia.     

Regional differences in left ventricular response to atrial pacing in the dog: mapping of segmental function by two-dimensional echocardiography

Two-dimensional echocardiography was applied in 10 closed-chest dogs to evaluate, in several left ventricular (LV) short-axis cross sections and subsegments, the regional contractile response to right atrial pacing. Compared with sinus rhythm (81 +/- 10 beats/min), which exhibited a moderate 7.2 +/- 12.0% (mean +/- standard deviation) base-to-apex increment in function, this gradient was significantly augmented to 34 +/- 12% by pacing at a heart rate of 180 beats/min. Measurements of wall thickening and perimeter shortening exhibited similar trends. Differences also were observed in subsegments of individual cross sections: in sinus rhythm the base-to-apex difference in function was relatively minor in the anterior and lateral aspects of the left ventricle (-9.1 +/- 18% and -1.9 +/- 19%), whereas a significant increase was noted in posterior and midseptal zones (18 +/- 17% and 22 +/- 30%). In response to pacing, the anterior and lateral wall base-to-apex gradients were significantly augmented (25 +/- 8% and 35 +/- 34%), but there was no further change in the posterior or septal regions. In conclusion, apical regions of the canine left ventricle responded to right atrial pacing with significant augmentation of contractile function, whereas more basal levels showed little response. Circumferentially, response to atrial pacing was most pronounced in the anterior and lateral segments.     

Symposium on infectious complications of neoplastic disease (Part II). Legionnaires' disease. Aspects of nosocomial infection

Tremendous progress has been made recently in characterization of Legionella pneumophila and infections caused by it. Certain areas that are particularly germane to immunosuppressed patients, who are affected more frequently than other patients, and areas that are controversial and merit particular consideration are considered herein. These include pathogenesis and correlation of experimental and clinical evidence, nosocomial outbreaks and almost ubiquitous distribution of L. pneumophila in water despite only a limited number of studies linking the two by aerosols, prevalence and possible reasons for the apparent spotty distribution, protean clinical manifestations, difficulties in diagnosis, certain aspects of therapy, and control by environmental changes.     

Derangements of myocardial metabolism preceding onset of ventricular fibrillation after coronary occlusion

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.     

Synchronized retroperfusion of coronary veins for circulatory support of jeopardized ischemic myocardium

A retroperfusion system was developed that augments retrograde delivery of arterial blood into an acutely ischemic myocardial region during diastole and facilitates coronary venous drainage in systole. An electrocardiogram-synchronized, gas-actuated bladder pump propels retroperfusate through an autoinflatable balloon catheter whose tip is placed within the regional coronary vein that drains the ischemic myocardium. Experiments were performed in 26 closed chest dogs with 4 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery. An untreated control series consisted of 13 dogs; the remaining 13 dogs were treated with retroperfusion, which was initiated after the first hour of acute coronary occlusion. Synchronized retroperfusion resulted in a significant 37 ± 10 percent (mean ± standard error of the mean) decrease in left ventricular end-diastolic pressure from 11 ± 2 to 5 ± 21 mm Hg, a 20 ± 4 percent decrease in peak systolic pressure (140 ± 7 to 110 ± 6 mm Hg) and a 25 ± 6 percent reduction in systemic vascular resistance (3,880 ± 340 to 2,380 ± 300 dynes sec cm⁻⁵). Ischemic region intracoronary S-T segment elevation decreased 40 ± 15 percent, and potassium loss was reduced 92 ± 22 percent. Partial pressure of oxygen measured distal to the coronary occlusion decreased 36 ± 2 percent, suggesting oxygen delivery to and extraction by the jeopardized ischemic myocardium. Ventriculography in four dogs revealed an increase in left ventricular ejection fraction and reversal of ischemic segment dyskinesia by synchronized retroperfusion. A nitro-blue tetrazollum study of 10 excised hearts indicated that 3 hours of synchronized retroperfusion significantly reduced the size of Ischemic Injury to 3.3 ± 2 percent of the left ventricle (versus 16.2 ± 5 percent in the untreated control group). In addition, retroperfusion appeared to correct ischemic arrhythmias.

The experimental data suggest that this treatment is capable of improving cardiac function and salvaging jeopardized myocardium. Clinical application is envisioned as a prompt temporary emergency support for acute and profound ischemic dysfunction not readily treatable by other interventions.     

Noninvasive in vivo and in vitro study of the St. Jude mitral valve prosthesis: Evaluation using two dimensional and M mode echocardiography,phonocardiography and cinefluoroscopy

Fifteen patients with clinically normal function of a St. Jude mitral valve prosthesis were studied with two dimensional and M mode echocardiography, Cinefluoroscopy and phonocardiography 8 to 292 days after valve replacement. The valve was readily imaged from the left sternal edge and cardiac apex in all patients. On two dimensional echocardiography from the long axis and four chamber views, minimal end-diastolic and endsystolic distances between the interventricular septum and prosthetic valve were 18 ± 5 mm and 13 ± 3 mm, respectively (mean ± standard deviation). On M mode echocardiography both leaflets were imaged throughout the cardiac cycle from the left sternal edge and their motion relative to the valve ring and to one another was easily evaluated. The apical transducer position permits quantitative assessment of individual leaflet motion. Maximal individual diastolic leaflet excursion was 8.7 ± 1 mm and the velocity of leaflet opening and closure was 364 ±103 and 678 ±115 mm/s, respectively.Asynchronous early closure of the posterior leaflet was observed during long cardiac cycles in six of seven patients with atrial fibrillation; the seventh patient had a rapid ventricular response and no long cardiac cycles. Diastolic fluttering of one or both leaflets was also seen during atrial fibrillation after rotation of the patient from the supine to the left lateral decubitus position. Three of the six patients with asynchronous leaflet closure underwent Cinefluoroscopy, and similar leaflet behavior was documented in all. An atrial systolic wave was inscribed in the valve echogram in six of eight patients with sinus rhythm.Phonocardiography recorded prosthetic valve opening and closing sounds occurring 60 ± 20 ms after aortic closure and 61 ± 12 ms after the QRS complex, respectively. The prosthetic valve opening and closure sound amplitude ratio was 0.11 ± 0.06.A clear plexiglass water bath phantom was fitted to a pulse duplicator and constructed so as to permit in vitro simulation of valve echograms under a variety of conditions. With this method, it was possible to reproduce or approximate all images obtained in patients from both echocardiographic transducer positions.     

Reflex and humoral responses to pulmonary embolism

The pathophysiologic response to pulmonary embolism involves mechanical blockade of the pulmonary vascular bed, release of humoral agents, and reflex responses involving receptors in the lung parenchyma and airways. Although not discussed above, arterial baroreceptor and chemoreceptor responses may also occur subsequent to hemodynamic and blood gas alterations. Most of the observations of pulmonary pathophysiologic and reflex responses of pulmonary embolism have been made in experimental animal models. Although these data appear to be applicable to patients with pulmonary embolism, detailed confirmation is lacking at this time. However, the animal observations can be extrapolated to patients with pulmonary embolism in describing many of the acute responses—tachypnea, shallow breathing, elevation of the hemidiaphragm, and abnormal blood gaseous exchange.     

Intracoronary thrombolysis in acute myocardial infarction

Forty-seven patients with acute myocardial infarction (MI) underwent intracoronary infusion of Thrombolysin or streptokinase. In 41, a completely reoccluded artery was reopened. Patency was associated with appearance of arrhythmias, relief of pain, gradual return of the ST-segment to the baseline and appearance of abnormal Q waves. Creatine kinase (CK) and MB-CK enzyme levels peaked earlier. Serial thallium scintigrams showed reduction in defect size after reperfusion, and the ejection fraction was higher compared with control. Eighteen patients were recommended for coronary bypass surgery for recurrent pain or severe multivessel disease.     

Focal and segmental glomerular sclerosis in reflux nephropathy

Reflux nephropathy was diagnosed in 23 patients (14 per cent of all the patients who received transplants) between 1973 and 1977, and nephrectomy was performed in all. Histology and immunofluorescence revealed a glomerular sclerosis associated with the idiopathic nephrotic syndrome. No focal and segmental glomerular sclerosis was seen in kidneys removed from patients with nonglomerular renal disease. Twenty-four hour urinary protein excretion in grams was 3.1 ± 0.3 (mean ± SEM) and was greater than that in our patients with end-stage nonglomerular renal disease. Thirty-one renal transplants were performed in these 23 patients; thereafter, maximum protein excretion was 1.4 g. Focal and segmental glomerular sclerosis was seen in only one (chronic rejection, protein excretion < 0.5) of the 20 kidneys available for histologic study. Thus, focal and segmental glomerular sclerosis is extremely common in reflux nephropathy, accounts for “glomerular” proteinuria and may contribute importantly to progressive renal failure but, unlike that associated with the idiopathic nephrotic syndrome, rarely recurs after renal transplantation.     

Characterization of left ventricular mechanical function during arrhythmias with two dimensional echocardiography: I. premature ventricular contractions

Two dimensional echocardiography was applied experimentally in the closed chest dog to quantitate left ventricular function during and immediately after single premature ventricular contractions induced through threshold stimulation at the apex. Coupling intervals were varied over a range from 35 to 85 percent of the R-R interval during normal sinus rhythm (920 to 980 ms). The quality of tomographic echocardiographic images during premature as well as postextrasystolic beats was found to be satisfactory for quantitating short axis section areas at end-diastole and end-systole. A systolic fractional area change was computed from two dimensional echocardiographic measurements to characterize mid ventricular cardiac function, which correlated significantly with peak left ventricular pressure and maximal first derivative of left ventricular pressure (dP/dt). Marked shortening of coupling intervals reduced fractional shortening during premature systole and enhanced the degree of potentiation during the postextrasystolic beat. By contrast, premature beats with relatively long coupling intervals caused less reduction in contraction and only minor postextrasystolic potentiation.Systolic shortening of left ventricular length as well as transverse diameters were studied in a two dimensional echocardiographic long axis cross section. During long coupling intervals contraction was normal except for distinct regional systolic outward “bulging” in the apical region. In contrast, short coupling intervals were associated with a more significant generalized derangement of ventricular wall motion during systole. It is concluded that the two dimensional echocardiographic method can be used to portray and quantitate global as well as regional left ventricular function during disturbances of cardiac rhythm.     

Prevention of ischemic injury and early reperfusion derangements by hypothermic retroperfusion

Hypothermic synchronized retroperfusion was applied during coronary artery occlusion to determine its ability to alleviate junctional derangements of reperfusion and to reduce infarct size. The proximal left anterior descending coronary artery was occluded in 25 closed chest dogs for 3 hours and then reperfused for 7 days. Thirteen dogs with no reperfusion pretreatment served as a control group (Group A). In 12 dogs, hypothermic retroperfusion was applied from 30 minutes up to 3 hours of the occlusion period (Group B). Sequential two-dimensional echocardiographic and hemodynamic as well as metabolic measurements were performed. Compared with untreated control dogs, dogs with hypothermic synchronized retroperfusion had significantly reduced heart rate and rate-pressure product, decreased left ventricular volumes and improved ejection fraction during the occlusion period. Two-dimensional echocardiographically-derived ischemic zone systolic fractional area change and systolic wall thickening indicated significantly improved function as a result of retroperfusion. During the reperfusion period, untreated control dogs (group A) had more severe derangements in hemodynamics and wall motion than dogs treated by hypothermic retroperfusion (group B). Mortality was 30.7% in group A, 16.7% in group B and 7th day infarct size as percent of the left ventricle was 12.0 +/- 6.5 (mean +/- standard deviation) and 4.2 +/- 5.9, respectively (p less than 0.02). It is concluded that hypothermic synchronized retroperfusion applied after coronary occlusion and before reperfusion significantly improves cardiac function during occlusion, minimizes complications of reperfusion and reduces the ultimate infarct size. Because this form of circulatory assistance helps maintain cardiac function and delays the evolution of myocardial necrosis, its application may be beneficial during an evolving acute myocardial infarction before achievement of surgical or nonsurgical reperfusion.     

A 6 year experience with the St. Jude medical valve: hemodynamic performance, surgical results, biocompatibility and follow-up

After in vitro testing (confirmed in vivo) of three contemporary valve designs (St. Jude, Bj?rk-Shiley and Carpentier-Edwards) demonstrated that the St. Jude valve possessed the most favorable hydrodynamic performance characteristics, a limited clinical trial was begun in high risk patients who might benefit from a prosthesis with improved hemodynamics. Between March 1978 and March 1984, 419 St. Jude prostheses (157 aortic, 156 mitral and 53 double aortic-mitral) were implanted in 366 patients. Ninety-six percent were in New York Heart Association functional class III or IV preoperatively. Early (30 day) mortality was 10.4% overall, and was lower after aortic (5.7%) or double (7.5%) than after isolated mitral valve replacement (16.0%). Forty-four prosthetic mitral valve recipients with severe ischemic mitral regurgitation experienced a 32% early mortality rate; without this group, mitral valve replacement carried a 10% early mortality rate (p less than 0.01). Multivariate logistic regression analysis confirmed that early death was strongly associated with three preoperative patient characteristics (p less than 0.05): ischemic mitral valve disease, depressed left ventricular function (ejection fraction less than 0.55) and advanced functional class (class IV). Late follow-up (7,055 patient-months, mean 22) was 99.7% complete (1 patient lost). Actuarial survival at 4 years was 80, 80 and 79% after aortic, mitral (nonischemic) and double valve replacement, respectively; in the subset with ischemic mitral regurgitation, actuarial survival was 34% (p less than 0.01). Eighty-six percent of survivors were in functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of left ventricular mechanical function during arrhythmias by two-dimensional echocardiography. II. Location of the site of onset of premature ventricular systoles

Two-dimensional echocardiography was applied experimentally in a closed chest dog model with intact pericardium to determine the location, magnitude and extent of contractile response during pacing from discrete ventricular sites. Midventricular short-axis tomographic images obtained during regular sinus rhythm and subsequent premature ventricular beats provided comparative measurements of global and segmental systolic changes of cross-sectional luminal areas and myocardial wall thickness. Computer-assisted standardized analysis of segmental systolic fractional area change and wall thickening was used to map left ventricular contraction during normal rhythm and premature beats of 70% coupling interval, induced alternately from anterior and lateral aspects of the mid-left ventricular short-axis cross-sectional plane. A characteristic pattern consisting of early systolic contraction and wall thickening was followed by paradoxical motion and wall thinning in late systole in segments corresponding to the region of direct electrical stimulation. Statistical analysis of segment by segment function indicated a maximal amount of premature beat contractile derangement at the site of the stimuli. Pacing from a right ventricular wall site in the midventricular plane caused a similar premature beat response at the anterior aspect of the interventricular septum. It is concluded that two-dimensional echographic analysis of segmental ventricular function can identify the location of electrical stimuli, and thus might noninvasively characterize regional patterns of contraction associated with ectopic foci during arrhythmias.