Hemodynamic effects of staged hematocrit reduction in patients with stable cor pulmonale and severely elevated hematocrit levels

Patients with cor pulmonale and high hematocrit levels are often subjected to phlebotomy in the belief that the adverse effects of high viscosity may outweigh the benefit of increased oxygen carrying capacity. To evaluate this, 12 patients with stable cor pulmonale and hematocrit values greater than 55 per cent were studied before and after a series of venesections. Right heart and aortic pressures, cardiac output and blood gases were measured at three mean hematocrit levels, 61 per cent (stage I), 50 per cent (stage II) and 44 per cent (stage III), with blood volume unchanged. From stages I to II, there were significant decreases in both mean pulmonary artery pressure and total pulmonary resistance. Oxygen transport fell but not oxygen consumption. Right ventricular end-diastolic pressure and cardiac output did not change. Right ventricular work either fell or was maintained by increased output. Frank-Starling performance (supine exercise) improved. No significant changes occurred with further reduction in hematocrit to normal levels (stage III). The findings of this study support the concept of overcompensating erythrocytosis in cor pulmonale, and the effects of moderate hematocrit reduction should not be overlooked in these severely ill patients.     

Superinfection: Another look

Superinfection in the compromised host often poses a diagnostic and therapeutic dilemma for the physician who is concerned that a perplexing array of microorganisms might be involved. We believe that the differential diagnosis list can often be narrowed considerably by separating superinfection in the compromised host into five convenient categories: (1) infections due to the underlying disease itself; (2) infections due to the underlying disease plus therapy for that disease; (3) infections due solely to medicaments, operations, or procedures; (4) infections increased in severity but probably not in incidence; and (5) societally related infections.Use of this or a similar categorization should result in a more rational approach to differential diagnosis, should encourage a more focused diagnostic work-up, should reduce the necessity for invasive procedures, should provide the microbiology laboratory information about specific organisms that should be sought sedulously, and should permit the selection of a more rational antimicrobial regimen prior to the availability of definitive microbiologic information.     

Cardiac function in alcoholics with cirrhosis: Absence of overt cardiomyopathy—myth or fact?

Cardiomyopathy in alcoholics is considered to be associated with a low incidence of hepatic cirrhosis. To evaluate cardiac hemodynamics in alcoholic liver disease, left ventricular function in 37 patients with hepatic cirrhosis (group II) was compared with that in 13 normal subjects (group I) matched for age, sex and cardiac size. These groups were contrasted with group III, comprising 32 alcoholics without cirrhosis who had cardiac symptoms but no cardiomegaly or heart failure. Patients with cirrhosis as a group did not differ from normal subjects (group I) in terms of left ventricular filling pressure and cardiac muscle and pump function (cardiac index). However, subgroup IIA (n = 21) had a stroke index significantly less than normal, while subgroup IIB had a significantly increased stroke index and myocardial cardial contractility with a diminished systemic arterial resistance. Similar hepatic abnormalities were present in both subgroups. In group III, left ventricular end-diastolic and aortic mean pressures were significantly elevated compared with values in normal subjects, while cardiac index and indexes of ventricular contraction and relaxation were abnormal. Further examination of patients with cirrhosis indicated that the responses to volume or pressure increments in terms of the level of stroke work for a given filling pressure were most abnormal in group IIA, approximating those of group III. Thus, although overt cardiomyopathy is infrequent in patients with cirrhosis, asymptomatic myocardial disease may assume clinical importance during volume or pressure overload.     

Introduction and epidemiology

An approach to infections in cancer patients is outlined that divides such infections into those due to underlying disease, those related to underlying disease plus therapy, and those related to therapy alone. The incidence of such infections in each of the categories is discussed, together with a general outline of patterns and trends in regard to involved microorganisms. Several specific areas discussed include: problems of superinfection with newer antimicrobial agents; the current inadequacy of diagnostic techniques; the potential for early treatment with monoclonal antibodies; the potential for augmenting one or more host defenses prior to sundering other defenses during antitumor chemotherapy; the potential value of a variety of nutrients that either may be depleted or might be of benefit in enhancing host defense mechanisms.     

Methamphetamine intoxication. A speedy new treatment

This communication describes the use of droperidol in methamphetamine poisoning. Droperidol antagonizes the central stimulatory effects of amphetamines producing a person who is indifferent to environmental stimuli, calm and cooperative. Coupled with an acid diuresis, causing a fivefold increase in the urinary concentration of methamphetamine and recovery of 66% of the ingested drug, a seriously intoxicated patient showed rapid improvement.     

Chronic inorganic mercury poisoning due to laxative abuse. A clinical and ultrastructural study

Chronic mercury poisoning developed in two patients following long-term daily ingestion of a laxative preparation containing mercurous chloride (calomel). There were major clinical manifestations attributable to toxic effects of mercury on the kidneys, gastrointestinal tract and central nervous system. Chronic renal failure developed in both patients and was manifested by elevated serum urea nitrogen and creatinine levels, with proteinuria but no abnormalities in the urinary sediment. Both patients showed evidence of renal tubular defects. Both patients had colitis with intractable watery diarrhea. In one, the colitis was so severe as to require a diverting colostomy. Dementia was present in both patients, with tremor a prominent feature in one. Tissue mercury levels were highest in the colon (526 μg/g; normal 0.10 μg/g) and kidney (421 μg/g; normal 2.75 μg/g); levels were also significantly elevated in the liver, brain, heart, pancreas, hair, skin, blood and urine. At autopsy both patients showed melanosis coli and blackening of the renal cortex. By electron microscopy the pseudomelanin granules in the colon were atypical in that they were intimately associated with ultra dense crystals identified by electron diffraction as beta mercuric sulfide. Crystals of beta ercuric sulfide were also associated with lipofuscin deposits in renal tubular epithelium and were present free and within macro-phages of the renal cortical interstitium and hepatic portal triads. Chronic mercury poisoning due to mercurous chloride-containing laxative preparations should be suspected in patients with a history of laxative abuse who present with unexplained renal failure, colitis, dementia or tremor.     

Progression of myocardial abnormalities in experimental alcoholism

To determine those characteristics of left ventricular functional and metabolic alterations in chronic ethanolism that may be time-dependent, up to 36 percent of total daily calories as ethanol was fed to dogs for an average of 18 months (study group 1) or 52 months (study group 2). The short- and long-term study groups were fed the same diet with vitamin supplements and were compared with simultaneously studied control animals. Left ventricular function was assessed in the intact anesthetized dogs using the thermodilution method for end-diastolic volume and stroke volume determinations. During preload increments with saline solution, a significantly greater increase in end-diastolic pressure was observed in both groups receiving ethanol as compared with the control animals; this increase was associated with reduced end-diastolic and stroke volume. However, the responses were similar in the short- and long-term study groups. Increased left ventricular collagen was the apparent basis for the compliance abnormality, but neither variable differed in the groups receiving ethanol.In contrast, the first derivative of ventricular pressure (dP/dt) normalized for preload and afterload, an index of left ventricular contractility, and the velocity of the contractile element (Vce) were significantly reduced only in the long-term study group while tissue calcium was normal. When chromium-51-EDTA was used as an extracellular marker, accumulation of water and sodium in myocardial cells was observed only in the long-term study group, without a reduction of cell potassium. In view of the dilatation of sarcoplasmic reticulum observed on electron microscopy, It is postulated that distortion of the tubular membranes may limit the rate of calcium availability to contractile protein and thus diminish contractile function in chronic alcoholism.     

Myocardial effects of long-term cigarette smoking: Relative roles of carbon monoxide and nicotine

In a prior study of an animal model exposed to long-term cigarette smoking, left ventricular performance was observed to decline in association with morphologic evidence of collagen accumulation. Because controversy has existed as to whether nicotine or carbon monoxide is the major pathogenetic agent in cigarette smoking, 18 young adult male beagles with chronic tracheostomy were placed in three groups of six dogs each: Group 1 served as a control group; group 2 received seven cigarettes of low nicotine content (0.2 mg/cigarette), which effected a peak carboxyhemoglobin level approximating 5/100 ml, similar to that of regular cigarettes; and group 3 received nicotine twice daily intramuscularly in an amount equivalent to seven cigarettes/day. In the intact anesthetized state, heart rate, left ventricular end-diastolic pressure and volume (indicator dilution) did not differ among the three groups. To assess relative myocardial wall stiffness, saline solution was infused into the left ventricular chamber. A significantly higher end-diastolic pressure and tension were elicited in group 3, suggesting a decrease in left ventricular compliance. No such change was observed in either group 1 or 2. Only long-term nicotine use was associated with increased hydroxyproline content in the left ventricular myocardium, suggesting a basis for enhanced stiffness. An index of left ventricular contractility was derived from the peak rate of rise of left ventricular pressure ($\text{dP}\text{dt}$), normalized for preload and afterload. Groups 1 and 2 showed no difference in this index (2.18 ± 0.3 versus 2.15 ± 0.18 muscle lengths/s per cm) at similar levels of aortic pressure, but the index was significantly lower (1.28 ± 0.12, p < 0.01) in group 3. Thus, the effects of long-term cigarette use on the myocardium appear to be predominantly dependent on nicotine rather than on carbon monoxide.     

Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition.

Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.     

Atherosclerotic ulcerative disease and associated aneurysms of the coronary arteries.

Abnormal cardiac muscle function has been reported in experimental diabetes mellitus from this laboratory. To examine left ventricular performance in diabetic patients without clinical evidence of myocardial ischemia or other cardiovascular disease, a noninvasive measurement of the systolic time intervals was carried out. Simultaneous recordings of the electrocardiogram, heart sounds, and carotid pulse were made in 25 diabetic subjects, 20 to 56 years of age, and compared with 37 normal subjects. The diabetic subjects had a shorter left ventricular ejection time, longer pre-ejection period, and a higher ratio of pre-ejection period/left ventricular ejection time (P < 0.001). The isovolumic time was prolonged (P < 0.001), while heart rate and arterial pressure were within normal limits. Abnormal function was independent of apparent duration and treatment by diet alone, insulin, or hypoglycemic agents. On the basis of available morphologic data in human and canine diabetes, an alteration of the myocardial interstitium may be the basis for this preclinical abnormality in diabetic patients.     

Association of monocytic leukemia in patients with extreme leukocytosis

Fifteen of 73 newly diagnosed patients with acute myeloid leukemia (AML), admitted to Mount Sinai Hospital between July 1977 and October 1979, presented with leukocyte counts greater than 100,000/μl. Eleven of these 15 patients with hyperleukocytosis had myelomonocytic (AMML-M4) or monocytic (AMOL-M5) leukemia compared to 14 of 58 patients with lower white cell counts (p < 0.001). Identification of type of leukemia, using the FAB classification, was based on morphology and special stains, including myeloperoxidase, Sudan black B, periodic acid-Schiff and nonspecific esterase with and without inhibition by fluoride. The proportion of patients with splenomegaly is higher in those with hyperleukocytosis (73 percent) than in those with lower white blood cell counts (p < 0.001) regardless of cell type. Leukemic infiltration of the skin, gums and central nervous system was seen exclusively in patients with AMML and AMOL. The serum lysozyme levels were significantly higher for all patients with AMML and AMOL regardless of the white blood cell count. The mean serum lysozyme for M-4, M-5 patients was 59.7 μg/ml compared to 18.9 μg/ml in patients with other cell types (p < 0.0001). Patients with a white blood cell count ≤100,000/μl had a complete remission rate of 69 percent compared to 47 percent for patients with higher white blood cell counts.     

A case of lymphoproliferative disease presenting as juvenile rheumatoid arthritis. Diagnosis by synovial fluid examination

Lymphoproliferative disease can present as arthritis, most commonly mimicking acute rheumatic fever. The finding of arthritis rarely leads to the correct diagnosis, in fact, it frequently suggests inflammatory rheumatic diseases. We present a case closely resembling juvenile rheumatoid arthritis in which the diagnosis was made by demonstration of malignant cells In the synovial fluid at a time they were absent from the peripheral blood and initial bone marrow specimen. Closed synovial and bone biopsy specimens, the latter of an osteopenic area, revealed the infiltrative character of this disorder.     

Primary aldosteronism. A study in contrasts.

Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia.     

Estimate of capillary permeability coefficients of canine heart to sodium and glucose

Measurements of fractional extraction (E) were used to study the transcapillary diffusion of sodium and glucose in isolated, nonworking, spontaneously beating dog hearts, perfused with blood of low hematocrit at controlled flows. Papaverine, dipyridamole, and norepinephrine were used, in separate experiments, to increase vascular conductance and capillary density. E-Sodium fell from 0.77 to 0.23 and E-glucose from 0.70 to 0.11 as plasma flow (F) was varied from 23 to 422 ml/min · 100 g. Permeability-surface area products (PS), calculated from PS = ?F ln (1 ? E), for both molecules increased progressively over the range of flows. Assuming S to be 500 cm²/g, capillary permeability coefficients were estimated from the maximal mean PS observed. Calculated P values (× 10^?5 cm/sec) for sodium and glucose were 3.91 and 2.13, respectively. The ratio of P-Na to P-glucose was analyzed statistically at various flow ranges. Mean $\text{P-}\text{Na}\text{P-}\text{glucose}$ ratios were proportional to the $\text{D-}\text{Na}\text{D-}\text{glucose}$ ratio (D, free-diffusion constant) at all flows greater than 40 ml/min · 100 g. Comparison of $\text{D-}\text{Na}\text{D-}\text{glucose}$ to $\text{D′-}\text{Na}\text{D′-}\text{glucose}$ (D′, restricted diffusion constant) at various pore radii showed that proportionality between Ps and Ds ratios is not a sufficient argument for free diffusion of Na and glucose across capillary walls.     

Acidosis of synovial fluid correlates with synovial fluid leukocytosis.

The antibacterial activity of aminoglycoside antibiotics is significantly reduced by lowering the pH of the incubation medium. Since gram-negative septic arthritis responds poorly to aminoglycoside antibiotic therapy, we sought to determine whether synovial fluid acidosis contributes to this poor outcome. Synovial fluid samples from 22 patients with various forms of acute and chronic arthritis were examined for white blood cell count and pH. A close correlation (r = -0.92, p is less than 0.001) between an increasing white blood cell count and a decreasing pH was demonstrated. Since septic arthritis is associated with high white blood cell counts, in synovial fluid, the resultant low pH may contribute to the poor response to gram-negative septic arthritis treated with aminoglycoside antibiotics.     

Ischemic heart failure: Sustained inotropic response to small doses of L-epinephrine without toxicity

As a prelude to a study of severe ischemic heart failure, the therapeutic response of the ischemic ventricle to epinephrine and acetylstrophanthidin in nontoxic doses was determined in 24 intact anesthetized dogs undergoing a first episode of acute regional ischemia. A thrombotic obstruction was produced in the left anterior descending coronary artery, effecting moderate left ventricular dysfunction. The elevation of end-diastolic pressure and reduced stroke volume in control dogs were not significantly altered by administration of strophanthidin. Epinephrine (0.05 μg/kg per min) elicited a significant reduction in end-diastolic pressure and increase in stroke volume. The latter was not attended by an increased incidence of ventricular fibrillation, whereas fibrillation occurred in half of the group given strophanthidin. Thus, the catecholamine was selected to study pump failure.Severe ischemic heart failure was assessed in two groups with scar from previous infarction for up to 4 hours. By 60 minutes of ischemia, the increase in end-diastolic pressure and volume and decrease in stroke volume and ejection fraction were comparable in both groups. Thereafter, alternate animals received small doses of epinephrine (0.05 to 0.15 μg/kg per min) with graded increments at 60 minute intervals to counter tachyphylaxis and findings were compared with those in control dogs. Over the subsequent 3 hours, there was progressive deterioration of left ventricular function in the untreated group with an increase in end-diastolic pressure from 10 ± 1 to 33 ± 2.4 mm Hg. End-diastolic volume increased by 63 percent; stroke volume and ejection fraction decreased by 48 and 66 percent, respectively. The infusion of epinephrine was attended by a significantly lower end-diastolic pressure of 20 ± 2.5 mm Hg, whereas end-diastolic volume, stroke volume and ejection fraction were restored to control levels after 4 hours of ischemia. Mortality in the untreated group was 62 percent by 4 hours; all seven animals in the treated group survived.     

Symptomatic normovolemic essential hypernatremia. A clinical and physiologic study

A 23 year old man presenting with episodic muscle paralysis and persistent normovolemic hypernatremia and hyperosmolality was investigated. Metabolic studies at the time of presentation and during a 10 hour fast, and the responses to acute and chronic water loading, alcohol, vasopressin and nicotine infusion, sodium restriction and intravenous sodium loading were all normal, with the exception of the acute water load. These results suggested abnormal hypothalamic function leading to an altered regulation of the central osmoreceptors controlling thirst and sodium metabolism; however, no central nervous system lesion was demonstrable. Despite normal levels of plasma [potassium], total exchangeable body potassium was reduced. It is proposed that the muscle paralysis was secondary to both the hypernatremia and the reduced total body potassium status. Progressive symptomatic improvement with lowering of plasma sodium and osmolality occurred following 24 months on a low sodium-high potassium-high fluid regimen although total body potassium status has remained low.     

Occupational lead nephropathy.

Among eight subjects suspected of excessive occupational exposure to lead, detailed examination of renal function identified abnormalities in four. Glomerular filtration rate was less than 87 ml/mim/1.73 m2 in one subject with asymptomatic renal failure, and in three subjects with preclinical renal dysfunction. In the subject with asymptomatic renal failure, chelation therapy increased the glomerular filtration rate, p-aminohippurate (PAH) extraction, the maximal PAH secretion rate (TmPAH) and improved proximal tubule ultrastructure, despite decreased renal plasma flow. This improvement in PAH transport was associated with correction of a proximal tubule defect in tritiated PAH uptake detected by section freeze-dry autoradiography of renal biopsy specimens. In three subjects, the etiologic diagnosis of lead-induced nephropathy was established by exclusion, but tubular dysfunction did not obviously exceed the reduction in blomerular filtration. Proximal tubule abnormalities were seen in each of the three patients who underwent biopsy. These studies suggest that lead nephropathy may be an important occupational hazard in the United States lead industry.     

Acute myelofibrosis in progressive systemic sclerosis. Report of a case developing during long term chlorambucil therapy and discussion of pathogenetic factors.

A case of acute myelofibrosis occurring in the course of long-term chlorambucil therapy for cardiac manifestations of progressive systemic sclerosis (PSS) is reported. Although hematologic malignancies have been known to develop consequent to long-term use of alkylating agents, and bone marrow suppression is well known, acute myelofibrosis has not, to our knowledge, been reported as a complication of this therapy, nor has any specific myeloproliferative syndrome been described consequent to such therapy in a patient with PSS. As abnormal fibroblastic proliferation is central to both PSS and myelofibrosis, it may be speculated that the patient with scleroderma may be predisposed to this particular expression of hematologic dyscrasia. The roles of fibroblastic proliferation, and immunologic and vascular factors in these two illnesses are currently poorly understood.