Sequential gold and penicillamine therapy in rheumatoid arthritis

Ninety patients with rheumatoid arthritis who had received courses of gold followed by penicillamine for their disease were evaluated to determine the predictiveness of a certain response or adverse reaction to gold for the same response or adverse reaction to penicillamine. Most patients who were considered gold-responders also responded to penicillamine, and most patients who did not respond to gold responded to penicillamine as well. Regarding toxicity, gold reactions did not predict reactions to penicillamine except that that patients with gold-induced proteinuria were at a higher risk for development of proteinuria during penicillamine therapy (p less than 0.001), and this usually occurred within the first six months of treatment. Patients with penicillamine-associated mucocutaneous reactions tended to have low gamma globulin levels (p less than 0.05) and were less likely to have subcutaneous nodules (p less than 0.05).     

Total occlusion of the left main coronary artery. A clinical, hemodynamic and angiographic profile

Although left main coronary artery stenosis has been extensively revicwed, total occlusion of the left main coronary artery has received scant attention. Six patients were diagnosed at cardiac catheterization as having total occlusion of the left main coronary artery over a period of seven years at two institutions. They ranged in age from 32 to 72 years, and all had symptoms ranging from NYHA Class 1-IV at initial presentation. One patient died three days after coronary artery bypass graft surgery. Of the remaining five, two treated medically are alive four and 40 months after catheterization, and three treated with coronary artery bypass graft surgery are alive three, 66 and 68 months after catheterization. Electrocardiogram showed prior myocardial infarction in three patients, stress tests were positive in three of four patients, and hyperlipidemia was present in the five tested. In the three patients without prior myocardial infarction, left ventricular function was preserved (ejection fractions = 0.52, 0.55 and 0.64; left ventricular end-diastolic pressures = 6, 9 and 14 mm Hg). Injection of the right coronary artery in this group revealed extensive collaterals filling the left coronary artery. The three patients with prior myocardial infarction had impaired left ventricular function (ejection fractions = 0.18, 0.30 and 0.33; left ventricular end diastolic pressures = 26, 35 and 35 mm Hg) and sparse intercoronary collaterals. Patients with total occlusion of the left main coronary artery have a varying clinical presentation and may have prolonged survival. In patients with good collaterals, left ventricular function may be preserved.     

Left ventricular dysfunction following acute myocardial infarction. A clinicopathologic and hemodynamic profile of shock and failure

The clinical, historic, hemodynamic and pathologic observations on 41 patients with shock following acute myocardial infarction are presented and compared with those on 38 patients in failure without shock. Patients with shock were divided into groups according to the presence or absence of ventricular or papillary muscle rupture (6 patients). Although over-all mortality for the 35 patients in shock without rupture was 77 per cent, subsets with varying survival rates could be identified based on the assessment of the hemodynamic state and heart size on roentgenograms. In survivors, mean cardiac index was 2. 1 liters/min/m², stroke work index 25 g-m/m² and left ventricular filling pressure 14 mm Hg; in nonsurvivors, these mean values were 1.3, 10 and 24, respectively. Heart size on roentgenograms and postmortem was increased in all those who died in both shock and failure groups whereas only 50 per cent of those who survived had cardiac enlargement. The patients who died in shock were found at autopsy to have major losses of left ventricular myocardium (approximately 40 per cent) from previous infarctions and the acute injury. Prognostic indices which accurately identify these high risk patients for aggressive therapy were derived based on discriminant analysis of the hemodynamic data. The various forms of circulatory and surgical support currently available and their potential usefulness are discussed. Finally, the comparison of ventricular performance for shock and failure groups describes a spectrum of impairment existing postinfarction which has been characterized by a three-dimensional analysis.     

Treatment of autosomal recessive lymphopenic agammaglobulinemia by transplantation of matched allogeneic bone marrow

A five month old male infant with autosomal recessive lymphopenic agammaglobulinemia (Swiss type) was treated by transplantation with unfractionated bone marrow from a sibling donor. The donor and recipient were well matched by cytotoxic and one-way mixed lymphocyte stimulation assays but differed in major blood group antigens. Evidence for establishment of both cellular and humoral immunity was obtained within two weeks of the transplant. Mucocutaneous candidiasis cleared, the skin test for Candida albicans became positive and normal numbers of phytohemagglutinin responsive lymphocytes appeared in the circulation. Antibodies to host erythrocytes appeared, and circulating immunoglobulin M (IgM) levels rose. A clinically mild graft-versus-host reaction was accompanied by the appearance of large lymphoblasts, similar to transformed lymphocytes, in the peripheral blood. The patient died of Pneumocystis carinii pneumonia 21 days after transplantation. Large numbers of lymphocytes and plasma cells were found in peripheral lymphoid tissues, but there was no histologic evidence for thymic lymphopoiesis. Adoptive transfer of immunocompetent cells, rather than differentiation of uncommitted stem cells, probably accounted for the appearance of immune functions.     

Estimating the likelihood of significant coronary artery disease

Among 23 clinical characteristics examined in 3,627 consecutive, symptomatic patients referred for cardiac catheterization between 1969 and 1979, nine were found to be important for estimating the likelihood a patient had significant coronary artery disease. A model using these characteristics accurately estimated the likelihood of disease when applied prospectively to 1,811 patients referred since 1979 and when used to estimate the prevalence of disease in subgroups reported in the literature. Since accurate estimates of the likelihood of significant disease that are based on clinical characteristics are reproducible, they should be used in interpreting the results of additional noninvasive tests and in quantitating the added diagnostic value.     

Left atrial transport function in myocardial infarction. Importance of its booster pump function.

After myocardial infarction (MI), left ventricular (LV) end-diastolic pressure (EDP) is higher than mean pulmonary artery wedge pressure because of powerful atrial contraction. To evaluate the significane of atrial contraction to left ventricular function we studied 10 control (C) patients without cardiac disease and 17 patients from three to six weeks after acute myocardial infarction. Cardiac catheterization with simultaneous left ventricular diastolic pressure (DP) and left ventricular cineangiograms were obtained. Left ventricular volumes and pressure were (mean +/- SD): (SEE ARTICLE). Although left ventricular stroke volume was lower in the patients with myocardial infarction than in the control subjects (46 versus 56 ml/m2), atrial contraction contributed more to left ventricular filling during diastole (which is the same as left ventricular stroke volume) in the patients with myocardial infarction than in the controls (16 versus 10 ml/m2). The average atrial contribution to left ventricular end-diastolic volume was 11.9 per cent (C), 15.4 per cent (MI); to left ventricular end-diastolic pressure 20 per cent (C), 38.7 per cent (MI); and to left ventricular stroke volume 21.7 per cent (C), 35.1 per cent (MI). Atrial contribution to left ventricular stroke volume was 56 per cent in patients with a cardiac index less than or equal to 2.0 liters/min/m2 and 31 per cent in those with a cardiac index greater than 2 liters/min/m2 (p less than 0.01). Atrial contraction contributed 35 per cent to left ventricular stroke volume in patients with normal end-diastolic volume and in those with increased end-diastolic volume and 10 per cent to end-diastolic volume in patients with increased end-diastolic volume (p less than 0.001). In patients with myocardial infarction, atrial contraction made a large contribution to left ventricular filling and stroke volume irrespective of the type of left ventricular functional derangement that was present. The "booster pump" function of the atrium cannot be ignored in assessing left ventricular performance.     

Patency of saphenous vein grafts five or more years after coronary bypass surgery.

The state of preservation of 48 coronary saphenous vein grafts was investigated by angiography in 27 patients from 60 to 79 months, average 64.6 months, after their insertion. Thirty-nine of the grafts (81.2 per cent) were patent; of these, 24 (50 per cent) were in excellent, six (12.5 per cent) in good, six (12.5 per cent) in fair and three (6.2 per cent) in poor condition. Nine grafts (18.8 per cent) were occluded. The rate of graft patency in this series compares favorably with that in shorter follow-ups and presages their further prolonged viability. Atherosclerotic obstructive graft disease may emerge as an important cause of late graft deterioration in an occasional patient.     

Resting U wave inversion as a marker of stenosis of the left anterior descending coronary artery

Resting 12-lead electrocardiographic records from 849 patients who underwent coronary cineangiographic studies were reviewed for U wave negativity without knowledge of the clinical data or angiographic results. In order to evaluate U wave negativity as an independent electrocardiographic sign, patients with significant Q waves in the anterior leads were excluded from the final data analysis leaving 760 patients. Twenty-seven patients had U wave negativity in leads I, a VL or V₄ through V₆. For the study population, the prevalence of coronary artery disease was 64 percent (484 of 760); the prevalence of significant left anterior descending or left main coronary artery stenosis was 46 percent (350 of 760); and the prevalence of angiographic left ventricular dysfunction was 41 percent (309 of 754). Among 27 patients with resting U wave negativity the prevalence of coronary artery disease was 89 percent (24 of 27); the prevalence of left anterior descending or left main disease was 89 percent (24 of 27); and the prevalence of angiographic left ventricular dysfunction was 80 percent (20 of 25). Among patients selected for coronary cineangiographic study, U wave negativity was a significant predictor (p <0.001) of ?75 percent stenosis of the left anterior descending or left main coronary artery and of left ventricular dysfunction (p <0.001).     

The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience

Although the occurrence of normal coronary arteriograms in patients with anginal pain is now recognized as a clinical entity, a large-scale study of such patients has not been reported. Accordingly, the historic aspects, laboratory findings and subsequent clinical course of 200 subjects (101 men and 99 women) with this syndrome were analyzed. Their average age was 47 years. No specific feature in the history could be discerned which separated these patients from those with angina due to coronary heart disease. The frequency of noncardiac sources of chest pain was similar in all patients. The electrocardiogram demonstrated abnormalities in the ST-T waves in slightly over 50 per cent of the patients, and the postexercise electrocardiogram was abnormal in another 20 per cent. Objective evidence for myocardial ischemia (myocardial lactate production) was three times more frequent in women than in men. The frequency of carbohydrate and/or lipid abnormalities was approximately half that in patients with coronary heart disease and did not correlate with the presence of myocardial ischemia. Long-term follow-up of these patients indicated that over half showed gradual improvement without specific therapy, whereas only 8 per cent had an increase in chest pain. Six patients died (four of unknown cause) in an average follow-up period of three years. Mortality, however, as determined by the life table method, was no greater than in a sex-age matched cohort derived from actuarial data. Although the etiology of this syndrome has not yet been demonstrated, its prognosis both in terms of persistence of pain and mortality appears to be benign.     

Aortocoronary bypass grafting in the management of patients with coronary artery disease.

There is widespread agreement that aortocoronary bypass grafting generally lessens the symptoms and functional limitations of patients with angina pectoris. Evidence for prolongation of life or prevention of myocardial infarction, arrhythmias and ventricular dysfunction is inconclusive. Harmful effects associated with surgical management of coronary artery disease can be documented in terms of operative mortality, perioperative myocardial infarction, graft occlusion and progression of occlusive disease in the native circulation. In this review of published experience, the accomplishments and the limitations of myocardial revascularization are considered in various clinical settings. Critical assessment of evolving information leads to the conclusion that widespread application of this procedure beyond the alleviation of symptoms refractory to medical therapy is not justified by present data.     

Right and left ventricular dysfunction in patients with chronic obstructive lung disease: Assessment by first-pass radionuclide angiography

To evaluate the relationship between right and left ventricular function in patients with obstructive lung disease, we studied 10 normal subjects (group 1) and 37 patients with chronic obstructive pulmonary disease by first pass radionuclide angiography. These 37 patients were divided into three groups: nine with mild chronic obstructive pulmonary disease (group 2), 20 with severe chronic obstructive pulmonary disease (group 3) and eight with severe chronic obstructive pulmonary disease and primary left ventricular disease (group 4). In each subject right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF) and ejection fraction during first third of systole (first third LVEF) were calculated. LVEF RVEF First-Third LVEF Group 1 0.60 ± 0.05 0.52 ± 0.03 0.29 ± 0.04 Group 2 0.61 ± 0.08 0.52 ± 0.03 0.29 ± 0.02 Group 3 0.58 ± 0.09 0.46 ± 0.091 0.24 ± 0.061 Group 4 0.51 ± 0.061 0.44 ± 0.091 0.20 ± 0.031 1 p < 0.05 versus 1. All subjects in group 2 had normal left ventricular and right ventricular function. In group 3,11 of 10 (55 per cent) had a low RVEF and three of 20 (15 per cent) a low LVEF. However eight of 20 in this group (40 per cent) had a depressed first-third LVEF. The correlation between decline in RVEF and first-third LVEF was good r = 0.73. We conclude that (1) certain indices of early systolic left ventricular ejection are abnormal in many patients with chronic obstructive pulmonary disease and correlate with the decline in right ventricular function; (2) this is not seen in patients with mild chronic obstructive pulmonary disease and is worse in patients with underlying left-sided heart disease.     

Congenital stenosis of the pulmonic and tricuspid valves. Clinical, hemodynamic and angiographic observations in a 20 year old woman

Patients with congenital stenosis of the tricuspid and pulmonic valves are rare, indeed, and are expected to have underdeveloped right ventricles. The three obstructions in series, namely, tricuspid orifice, right ventricular inflow and right ventricular outflow typically result in symptomatic, cyanotic infants or young children with right to left shunts at atrial level. We present unique clinical, hemodynamic and angiographic information on a 20 year old acynotic, virtually asymptomatic woman with normally formed right ventricle and congenital stenosis of the tricuspid and pulmonic valves.     

Nonrandom occurrence of single-vessel coronary artery disease

The location of obstructive coronary artery lesions in single-vessel disease is nonrandom. The circumflex coronary artery is protected relative to the right coronary artery. This may have important implications regarding the causation of coronary obstructive lesions.     

Myocardial metabolism and threshold to angina in coronary artery disease after digitalization: responses at rest and during stress.

To determine the metabolic cost of digitalis to patients with coronary artery disease who were not in congestive heart failure, 15 patients were stressed with atrial pacing before and after the administration of ouabain (0.007 mg/kg). Resting coronary sinus blood flow (118 ± 31 ml/min) and myocardial oxygen consumption (15.8 ± 3.5 ml oxygen/min) increased to 141 ± 25 ml/min (P < 0.05) and 19.8 ± 3.8 ml oxygen/min (P < 0.02) after ouabain administration, but there was no shift to lactate production and no angina. Atrial pacing before and after the infusion of ouabain induced a shift to lactate production (before ouabain: +29 per cent to -3 per cent, P < 0.05; after ouabain: +36 per cent to ?2 per cent, P < 0.01), caused angina in 12 patients (80 per cent) and S-T segment depression in nine patients (60 per cent) whether ouabain was given or not. Furthermore, atrial pacing alone versus atrial pacing plus ouabain produced no significant differences in coronary sinus blood flow (178 ± 63 to 181 ± 90 ml/min) and myocardial oxygen consumption (22.8 ± 6.6 to 23.5 ± 10.1 ml oxygen/min). Yet, 11 of 12 patients (92 per cent) experienced angina within a much shorter period of time after the institution of atrial pacing (152 ± 119 seconds to 46 ± 41 seconds, P < 0.01) if they had previously received ouabain.These findings indicate that digitalization increases myocardial oxygen consumption in nonfailing hearts with coronary artery disease but that this increase is not accompanied by a shift to anaerobic metabolism at rest. Although prior digitalization does not appear to produce additional deleterious metabolic effects during stress, it may sensitize patients to a much earlier awareness of angina.     

Multisystem involvement in chronic liver disease. Studies on the incidence and pathogenesis

Sjögren's syndrome occurred in 37 per cent, renal tubular acidosis in 32 per cent, pulmonary diffusion defects in 26 per cent and peripheral neuropathy in 10 per cent of patients with active chronic hepatitis, primary biliary cirrhosis or cryptogenic cirrhosis. The incidence of certain other conditions determined from clinical features alone was lower; these included arthropathy in 14 per cent, thyroid disorders in 10 per cent, skin lesions in 17 per cent and colitis in 5 per cent. In the complete series of 218 patients, 125 (57 per cent) had involvement of at least one organ other than the liver, such involvement being significantly more common in those with active chronic hepatitis (63 per cent of cases) and primary biliary cirrhosis (68 per cent) than in those with cryptogenic cirrhosis (38 per cent). In a number of patients, prednisone therapy was followed by both subjective and objective improvement in the features of the multisystem involvement.No correlation could be found between multisystem involvement and the presence of mitochondrial, smooth muscle or antinuclear antibodies in the serum or with the serum levels of immunoglobulins A (IgA), M (IgM) and G (IgG). Histologie examination of the various organs disclosed dense infiltration with small lymphocytes, suggesting that delayed hypersensitivity reactions were involved in the production of tissue damage. In support of this was the demonstration of cell-mediated reactivity in vitro to salivary or renal antigens in 42 per cent of the patients with Sjögren's syndrome and in 62 per cent of those with renal tubular acidosis, respectively.These findings, together with the frequency and similar pattern of multisystem involvement in the three conditions, suggest a common pathogenetic mechanism, and disordered cellular immune reactions directed primarily against the liver could affect other organs as a result of cross antigenicity.     

The importance of type IV hyperlipoproteinemia as a predisposing factor in coronary artery disease

One hundred seventy-six consecutive patients were evaluated for the frequency of potentially reversible risk factors associated with coronary artery disease. The results In a group of 105 patients with objective coronary artery disease was compared with a control group of 71 patients without coronary disease. The prevalence of risk factors was examined in the entire group of 176 patients and in a young subgroup of 55 patients with coronary disease who were under 50 years of age.Obesity was the most prevalent risk factor for the whole group but was especially significant for the young patient with coronary disease. Type IV hyperlipoproteinemia, the most prevalent lipoprotein disorder in the study, was significantly elevated in the entire group as well as in the young patients with coronary disease. An abnormal glucose tolerance test was another feature of the young patients with coronary disease. Although some men with coronary disease did not have a predisposing metabolic abnormality, no woman in the study had coronary disease if a metabolic abnormality was not present. These findings emphasize the metabolic nature of coronary artery disease as well as the atherogenic potential of type IV hyperlipoproteinemia.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.