Extramedullary plasmacytomas following successful radiotherapy of Hodgkin's disease. Clinical and immunologic aspects

A patient with multiple extramedullary plasmacytomas is described, with particular attention to the protein abnormalities. A lambda type Bence Jones protein and elevated serum levels of immunoglobulin D (IgD) were demonstrated as well as the in vitro biosynthesis of the lambda light chain by the plasma cells from a subcutaneous plasmacytoma. It seems probable that the particular clone of cells studied in vitro retained only the ability to manufacture the lambda type light chain.     

Bullous photoreaction to nalidixic acid

Cutaneous blisters developed after exposure to the sun in two women who were taking nalidixic acid. Blisters continued to appear even after therapy was discontinued and there was no further exposure to the sun. Phototesting showed abnormal sensitivity to both short and long wavelength ultraviolet spectra in one patient. The low incidence of this phenomenon suggests a photoallergic mechanism, but features of both photoallergy and phototoxicity are present.     

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.     

Immunodeficiency, malabsorption and secretory diarrhea. A new syndrome.

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.     

Clinical manifestations of mannosidosis—A longitudinal study

Mannosidosis is a partially defined disorder of glycoprotein metabolism; less than 20 cases have been reported in the literature. In this work, a longitudinal study of five new patients is presented in an attempt to delineate the phenotype and clinical course of this unusual storage disease. The data on our patients and those in the literature indicate that people with mannosidosis appear normal at birth and that their typical phenotype develops by two years of age. This is characterized by a distinctive coarse facies and dysostosis multiplex. Although recurrent Infections, hearing loss and mental retardation occur, the course in this storage disorder generally is stable and is compatible with adult life.The diagnosis is confirmed by the presence of a deficiency in α-D-mannosidase activity in leukocytes or fibroblasts, by the presence of vacuolated lymphocytes in peripheral blood and foam cells in bone marrow, and an increased excretion of mannose-rich oligosaccharides in urine.     

Current therapy of hypertension. A pharmacologic approach.

Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside.     

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.     

Protein digestion and absorption in man. Normal mechanisms and protein-energy malnutrition.

Protein is an essential nutrient normally assimilated in an efficient manner following the action of gastric, pancreatic and small intestinal enzymes. After hydrolysis, protein digestion products in the form of amino acids and small peptides undergo mucosal uptake by distinct transport mechanisms. Although gastric and pancreatic enzymes are important, the small intestine appears to be the critical rate-limiting tissue in this process. Impaired intake, assimilation or excessive enteric protein loss may occur with several diseases leading to protein-energy malnutrition. Although the clinical and laboratory features of this condition are nonspecific and wide ranging in spectrum, their presence may provide a clue to underlying disease and serve as an index of patient nutritional status. Disease of the exocrine pancreas or small intestine may cause significant protein-energy malnutrition which, in turn, can cause major structural and functional abnormalities in these tissues.     

Osteosclerosis in primary hyperparathyroidism.

Osteosclerosis in adults with primary hyperparathyoidism is rare; the usual skeletal manifestation, when presented, is diffuse osteropenia. We describe a patient with generalized osteosclerosis in association with primary hyperparathyroidism. The findings are documented by conventional and fine-detail radiography, absorptiometric bone mineral analysis, quantitative microradiography and histologic examination of bone. The unique features are contrasted with the manifestations recorded in a recently studied group of 87 hyperparathyroid patients. The data presented here support a causal relationship in this patient between parathyroid hormone excess and the development of densely sclerotic bones.     

Salmonella heidelberg enteritis and bacteremia. An epidemic on two pediatric wards.

Symptomatic infection with Salmonella heidelberg developed in 55 children after their admission to the pediatric wards of two adjacent hospiatls in San Juan, Puerto Rico. Many of these children had been hospitalized for the treatment of diarrhea of unidentified etiology. In 25 of these patients, Salmonella bacteremia was documented. Five had clinically unsuspected and untreated bacteremia with no evidence of complications during the follow-up period of four and a half months. The remaining 30 had "standard" symptomatic infection due to S. heidelberg. Eight children died; four of these proved to be bacteremic. The index patient, who also introduced the infection into one of the hospitals, was identified. Person to person spread perpetuated the outbreak within and between the two hospitals for nearly four months. Although neonates with salmonellosis had a higher rate of bacteremia than other children, no other specific predisposing factors for Salmonella bacteremia were identified. Laboratory studies of the epidemic strain revealed neither invasive nor enterotoxic properties of the organisms, nor enhanced virulence in laboratory mice. Cohort nursing and isolation of patients with positive cultures halted the epidemic. Nontyphoid Salmonella bacteremia, sometimes clinically unsuspected and self-limited, should be recognized as a frequent accompaniment of Salmonella enteritis in young hospitalized children.     

Multiple adenocarcinomas and premalignant changes in "backwash" ileitis.

In a patient with long-staning ulcerative colitis and "backwash" ileitis, multiple carcinomas developed in the colon and ileum. In both locations premalignant mucosal changes of the basal cell proliferation type were seen adjacent to and remote from sites of carcinoma. Although the frequency of such premalignant and malignant changes in "backwash" ileitis is unknown, their concurrence in this case suggests that ulcerative colitis involving the terminal ileum increases the risk of small bowel carcinoma.     

The evolution of alpha heavy chain disease

Two patients with alpha heavy chain disease are described. In the first patient, treatment with cyclophosphamide, prednisone and doxycycline was associated with a 28 month-long remission and the disappearance of the paraprotein and lymphoplasmocytic infiltration of the intestine. Shortly afterwards, a retroperitoneal immunoblastic lymphoma was found associated with an immunoglobulin G-kappa-paraproteinemia, and gamma heavy and kappa-light chains in the urine; the intestinal biopsy specimen was normal. In the other patient, the alpha chain only appeared two years after the malabsorption syndrome. The fact that in the first, apparently cured patient, a tumor of different anatomic site and secretory capacity appeared, suggests the existence of a B-cell neoplasia of different clone from that which gave rise to the original disease. In the second patient, it is probable that only the increase in the mass of neoplastic cells led to the detection of the protein abnormality, or alternatively the antigenic-oncogenic stimulus led to the abnormal secretion only after two years.     

Alterations in left ventricular mass and performance in patients treated effectively for thyrotoxicosis. A comparative echocardiographic study.

The effect of successful therapy for thyrotoxicosis on left ventricular mass in human subjects has not been documented. Furthermore, assessment of intrinsic left ventricular pathophysiologic changes associated with hyperthyroidism has been limited by the difficulty of justifying invasive studies in these patients. Echocardiography is a suitable method of assessing cardiac dimensions and function in patients with thyrotoxicosis.Echocardiographic studies were performed on 15 thyrotoxic patients, mean age 36 years, prior to and 12 months after the initiation of effective antithyroid therapy. The clinical diagnosis and results of therapy were confirmed by the measurement of serum thyroxine levels. Therapy produced a significant decrease in heart rate (108 to 78 beats/min; p < 0.001), arterial pulse pressure (60 to 45 mm Hg; p < 0.02) and echocardiographically estimated cardiac output (6.49 to 3.84 liters/min; p < 0.001).There was a significant reduction in left ventricular mass from 135 to 96 g (p < 0.001). The mean velocity of circumferential fiber shortening was reduced from 1.13 to 0.81 cire/sec (p < 0.001), a change that correlated significantly with the decrease in heart rate (r = 0.66, p < 0.01). A minimal reduction in left ventricular diameter was found (4.7 to 4.5 cm; p < 0.05), whereas end-systolic diameter and shortening fraction remained unchanged. Four patients failed to repond to initial antithyroid therapy. The size of the left ventricular mass increased in these patients after unsuccessful therapy.This study shows that effective treatment for thyrotoxicosis is associated with a reduction in the size of the left ventricular mass. The correlation between alterations in heart rate and mean velocity of circumferential fiber shortening following effective therapy suggests that the changes in myocardial contractility in these hyperthyroid patients may be predominantly a negative chronotropic effect. Minimal changes in end-diastolic diameter without changes in end-systolic diameter tend to confirm that myocardial contractility is altered by the state of thyroid activity independent of the Frank-Starling mechanism.     

Angina pectoris among 10,000 men. 5 year incidence and univariate analysis

In 1963, 10,000 men aged 40 years and over were examined; those without myocardial infarction or angina pectoris were followed for the next 5 years (1963–1968) to see what factors (variables) found in 1963 were associated with the development of angina pectoris by 1968.The average annual adjusted incidence for angina pectoris was 7.2/1,000; the incidence was highest (11.2) in those bom in Southeastern Europe and lowest (3.8) in those born in the Middle East. The incidence rose with age until age 59 and then plateaued off.The variables found significantly associated (p <0.01) with the development of angina pectoris were as follows: Clinical—blood pressure (systolic and diastolic), intermittent claudication, diabetes mellitus, nonspecific T waves in the electrocardiogram, serum cholesterol (total and in beta-lipoprotein). Psychosocial—anxiety and severe problems as seen by the subject in whatever area of his life situation, as well as, or because of, moving from one country to another. Blood group—A1BJk^a?. In addition, overweight, peptic ulcer and lack of physical activity are probably of importance.A knowledge of the factors associated with the development of angina pectoris is a “sine qua non” for the clinician who is interested in preventing the condition or aiding the patient who already has it.     

Angina pectoris among 10,000 men: II. Psychosocial and other risk factors as evidenced by a multivariate analysis of a five year incidence study

The major independent role played by anxiety and severe psychosocial problems (especially family ones) is demonstrated by this multivariate analysis of a five year prospective study of the development of new angina pectoris among almost 10,000 adult men (average annual incidence = $\text{5.7}\text{1,000}$).The independent effect of these two variables is considerably augmented by the other significant risk factors of age, total serum cholesterol, systolic or diastolic blood pressure, certain electrocardiographic abnormalities and diabetes mellitus. The presence of all seven risk factors (at a high level) increases the probability of angina pectoris developing within five years to $\text{289}\text{1,000}$ from $\text{14}\text{1,000}$, when these factors are low or absent.The wife's love and support is an important balancing factor, which apparently reduces the risk of angina pectoris even in the presence of high risk factors. The implications of these findings to the pathophysiology and prevention of angina are stressed.     

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.     

Acquired bullous disease of the skin and solitary amyloidoma of the lung

A 70 year old black woman had a 1 year history of bullae occurring at points of trauma without preceding inflammation. She was also found to have a solitary amyloidoma of the upper lobe of the left lung and no signs of amyloidosis elsewhere. Her general health, except for mild chronic bronchitis, was good.     

Immunopathologic features of a patient with glomerulonephritis and pulmonary hemorrhage

Described here is a patient who had pulmonary hemorrhage associated with glomerulonephritis. Serologic data revealed the presence of circulating cold agglutinins, a positive Coombs test and positive antinuclear factor. Serum total hemolytic complement levels and serum complement component Clq levels were low throughout the patient's course. The patient also exhibited precipitating antibodies against calf thymus nuclear extract and rabbit liver ribosomes. In addition, rheumatoid factor precipitable material was detected in the serum early in the patient's course. Immunofluorescent studies revealed deposition of immunoglobulin G (IgG) on the glomerulus in a pattern analogous to that which occurs in experimental “immune-complex” induced glomerulonephritis. Our findings suggest that the patient's disease was associated with circulating and deposited antigen-antibody complexes. The pathogenesis of the renal lesion in this instance is therefore distinctive from that previously described in patients with pulmonary hemorrhage and nephritis and said to have Goodpasture's syndrome, which is usually associated with antiglomerular basement membrane antibodies.     

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.