Gaucher's disease associated with Hodgkin's disease

A patient with chronic adult-onset Gaucher's disease is described. The diagnosis was based on the finding of typical Gaucher cells in the spleen, liver and bone marrow associated with deficiency of glucocerebrosidase. The patient also had Hodgkin's disease, nodular sclerosis type, stage III. The patient is alive and relatively well six years after presentation, having been treated with a combination of chemotherapeutic regimens.Previously reported cases of Gaucher's disease concurrent with Hodgkin's disease are reviewed.     

Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort

The serum levels of estradiol and testosterone as well as established risk factors for coronary heart disease were estimated in 61 men (mean age 70.0 ± 6.4 [SD] years) with coronary heart disease and in 61 matched control subjects enrolled in the Framingham Heart Study. The mean serum estradiol level was significantly higher in the subjects with coronary disease (p = 0.011). This difference in estradiol level increased with the exclusion of subjects older than 75 years (p < 0.001). The mean serum testosterone level was not significantly different. None of the established risk factors for coronary heart disease was different between subjects with coronary disease and control subjects except blood glucose level, which was higher in the subjects with coronary disease (p = 0.025). We conclude that hyperestrogenemia is an important correlate of coronary heart disease in men.     

Evidence for hyperestrogenemia as the link between diabetes mellitus and myocardial infarction

The previous findings of hyperestrogenemia in men with myocardial infarction and of a correlation between the ratio of serum estradiol to testosterone and the glucose-insulin-lipid defect have led to the hypothesis that hyperestrogenemia may be responsible for the increased incidence of atherosclerosis and its complications in patients with diabetes. The hypothesis predicts that the mean serum level of estradiol and the ratio of serum estradiol to testosterone are elevated in patients with diabetes. To test this hypothesis, the serum levels of estradiol and testosterone were measured in 21 nonobese men with diabetes and in 19 apparently healthy men of similar age and weight. A higher mean serum estradiol level (p less than 0.001) and estradiol-to-testosterone ratio (p less than 0.005) were observed in the patients with diabetes, whereas the mean serum testosterone level was not significantly different. The findings are consistent with the hypothesis.     

Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium. Further implications on the role of the von Willebrand factor in hemostasis

The platelets of two patients with the Bernard-Souller (giant platelet) syndrome were not aggregated by bovine factor VIII. Platelet aggregation by rlstocetin was also absent and, in contrast to the findings in von Willebrand's disease, this defect was not corrected by human factor VIII. The platelets of patients with the Bernard-Soulier syndrome may lack a receptor for the von Willebrand factor activity of factor VIII (VIII_VWF), whereas the abnormal platelet function in von Willebrand's disease is due to a decreased level of VIII_VWF in their plasma. As in the latter disorder, the adhesion of platelets to subendothellum was impalred in the two patients with the Bernard-Souller syndrome that we studied. These findings provide further evidence that VIII_VWF, through its effect on platelets, plays an important role during the primary arrest of bleeding.     

Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases

Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency.     

Isolated deficiency of platelet procoagulant activity

This is a study of a 34 year old woman with a moderate to severe bleeding disorder in whom impaired platelet procoagulant activity (PPA) was found by several methods, including tests of factor 3 availability (PF-3a), prothrombin consumption and contact activation. No deficiencies of platelet adhesion, aggregation, secretion, metabolism or granule-bound substances were detectable. Under adequate platelet coverage, this woman underwent two surgical procedures without difficulty. These findings demonstrate the role of PPA in hemostasis and indicate that a defect in PPA can be an isolated occurrence. The abnormalities in PF-3a found in this patient could be due to the diminished number of factor V binding sites, resulting in impaired factor Xa binding, found in separate studies by Majerus et al.     

Heparin therapy in a patient bitten by a saw-scaled viper (Echis carinatus), a snake whose venom activates prothrombin

Disseminated intravascular coagulation developed in a 28 year old man who was bitten by a saw-scaled viper (Echis carinatus). He also became severely anemic, and this may have been the result of both hemorrhage and a microangiopathic hemolytic anemia. After therapy with fibrinogen and antivenin failed to correct his coagulation defects, he was treated with heparin. Four days later, all coagulation studies were normal and the patient recovered rapidly. In vitro studies showed that the venom of this snake activates prothrombin directly. This procoagulant effect was enhanced by a calcium-lipid mixture and by factor V. In platelet-rich plasma, heparin inhibited both venom-induced platelet aggregation and clotting, and this may explain its effectiveness in correcting the coagulation defects in the patient. Heparin may be useful in treating the bites of some other snakes whose venoms activate the coagulation mechanism.     

Methyldopa hepatitis: A report of six cases and review of the literature

Six cases of methyldopa hepatitis, including two in which the patients died are reported; and 77 cases from the literature are reviewed. Patients in whom severe hepatotoxic reactions to methyldopa develop usually complain of prodromal symptoms typical of hepatitis, often with fever, one to four weeks after therapy is initiated. Jaundice, when it occurs, is usually manifest within three months.

Asymptomatic, transient elevations of serum transaminase levels may occur in patients receiving methyldopa. However, since the clinical and histologic features of hepatic injury from methyldopa are indistinguishable from viral hepatitis, it is suggested that the incidence of this iatrogenic disease is higher than generally appreciated.

Serum transaminase levels should be determined at the initiation of therapy with methyldopa and four weeks later. Moreover, any patient who has unexplained fever or the prodromal symptoms of hepatitis should undergo liver chemistry studies immediately.     

Dynamic intercoronary collateral flow in a patient with variant angina and coronary artery spasm

Intermittent intercoronary collateral flow was observed in a patient with coronary vasospasm associated with variant angina. Collateral flow began almost immediately after total occlusion of the right coronary artery, but did not prevent pain or S-T segment elevation. Some collateral vessels may pre-exist ischemic conditions and flow across these channels may be immediately dependent on the pressure gradient across them.     

Sudden death during ambulatory monitoring. Analysis of six cases

The ambulatory electrocardiographic recordings of six patients with coronary artery disease who died during monitoring were analyzed. In four patients, sinus rhythm was interrupted by sinoatrial, atrioventricular, nodal, or infra-His conduction abnormalities leading to bradyarrhythmic sudden death. Two patients died of sustained ventricular tachycardia or ventricular fibrillation. These data emphasize that the arrhythmias involved in the sudden death syndrome may be more heterogenous than currently appreciated.     

Acute pulmonary edema due to ischemic heart disease without accompanying myocardial infarction: Natural history and clinical profile

The natural history of acute cardiogenic pulmonary edema was studied in a group of patients who did not have acute myocardial infarction, cardiomyopathy, or valvular heart disease. Most of these patients had coronary artery disease. Cardiac catheterization in selected patients showed depressed contractility in some with segmental abnormalities. In the group older than 70 years, this carried a 70 percent two-year mortality rate. It is important to approach patients with this syndrome vigorously, both diagnostically and therapeutically. Acute, reversible segmental ischemia may be responsible for this syndrome and may respond to measures designed to prevent recurrent ischemia.     

Studies of twins with systemic lupus erythematosus: A review of the literature and presentation of 12 additional sets

To assess the role of genetic factors in systemic lupus erythematosus (SLE), 12 twin pairs (seven definitely monozygotic, three definitely dizygotic) of which one or both twins had SLE, were studied and compared to 17 twin pairs (12 definitely monozygotic) previously described. In the present series, four of seven (57 per cent) definitely monozygotic pairs were clinically concordant for SLE, satisfying the preliminary criteria of the American Rheumatism Association (ARA). Concordance for the presence of antinuclear factor (ANF) and hypergammaglobulinemia was 71 and 87 per cent, respectively. These data closely agree with those on the 12 definitely monozygotic sets previously described. All three of the dizygotic sets in the present series were discordant for clinical SLE, although one clinically well twin had marked serologie abnormalities.Comparison of these data with those from other first degree relatives of our twins clearly suggests a strong genetic component in the pathogenesis of SLE. The relative contribution of nongenetic and environmental factors to the expression of the disease is discussed.     

Chorea complicating oral contraceptive therapy: Case report and review of the literature

Oral contraceptive-induced chorea occurs infrequently; therefore, this serious complication of birth control pills may be generally unrecognized as a potential side effect. A patient with oral contraceptive-induced chorea is described and a review of the literature presented. A previous episode of chorea predisposes towards estrogen-progesterone-induced chorea; therefore, other methods of contraception should be considered in patients with a past medical history of Sydenham's chorea or chorea gravidarum. Vascular, immunologie and neurotransmitter abnormalities are discussed as possible etiologies for gestational steroid-induced chorea.     

Diffuse intrapulmonary hemorrhage,renal failure and a systemic vasculitis: A case report and review of the literature

A 63 year old woman was hospitalized with massive hemoptysis, anemia and renal failure. Despite intensive supportive care, she died soon after admission. Autopsy revealed diffuse necrotizing alveolitis, rapidly progressive glomerulonephritis and a systemic vasculitis. Massive intrapulmonary hemorrhage with hemoptysis is an unusual complication of a systemic vasculitis. The case is discussed and the literature reviewed.     

Use of cefotaxime, a beta-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms

Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents.     

Relapses after interruption of cyanocobalamin therapy in patients with pernicious anemia

One or more episodes of recurrent megaloblastic anemia occurred in 36 (10.8 percent) of 333 patients with pernicious anemia following interruption of therapy. Treatment had most commonly been discontinued by patients because they felt well, or by physicians due to error. Thirty-five episodes of recurrent cobalamin deficiency were analyzed in detail. In the 24 patients in whom the exact date of cessation of therapy was recorded, the mean interval before relapse was diagnosed was 64.5 months (range 21 to 123 months). Recurrence manifested as macrocytosis in the absence of anemia occurred earlier (mean, 49.2 months) than that associated with anemia (73.1 months). A weak correlation was apparent between the amount of previous cyanocobalamin treatment and time to relapse. One third of relapses were unrecognized and left untreated for more than two years, white usually stow hematologic progression occurred. Recurrences of cobalamin deficiency in individual patients exhibited mimetic features. Further study is necessary to establish the optimal dosage and frequency of maintenance therapy in pernicious anemia.     

Postpartum amenorrhea, diabetes insipidus and galactorrhea. Report of a case and review of the literature

A 26 year old woman presented with postpartum amenorrhea, galactorrhea, diabetes insipidus and hypopituitarism. This occurred in the absence of postpartum hemorrhage or shock. Plasma prolactin levels were within normal limits. To our knowledge, this is only the second reported case of such an association of clinical findings; the possible pathogenesis is discussed.     

Candida peritonitis: Report of 22 cases and review of the english literature

Thirty-one patients with Candida isolated from peritoneal fluid were examined. Twenty-two were considered to have Candida peritonitis. The data on these 22 patients, plus 12 additional patients described in the literature, were reviewed. This infection was observed as a complication of peritoneal dialysis, gastrointestinal surgery or perforation of an abdominal viscus. Recent antibiotic administration seemed to be an important predisposing factor. The disease usually remained localized intra-abdominally, although disseminated candidiasis was also noted in three cases. Clinically significant infection could be differentiated from peritoneal contamination with Candida by the presence and persistence of fever, peritoneal signs, peripheral leukocytosis, positive peritoneal cultures for Candida, abnormal films of the abdomen and purulent ascitic fluid. Surgical interventions and removal of infected peritoneal fluid were the cornerstones of therapy. Short-term, low-dose systemic and/or intraperitoneally administered amphotericin B appeared promising in the treatment of unremitting infection. Mortality in treated patients was low and was comparable to that in patients with bacterial peritonitis.     

Cardiac failure in Addison's disease

In an average 30 years of follow-up study, seven of 22 patients with primary adrenal insufficiency have had cardiac failure. Comparison of these seven with the 15 who remain free of this complication revealed that the former group were somewhat older and had higher incidences of unrelated cardiac disease and of nonsteroid-dependent hypertension, but that their replacement regimens, with respect to sodium supplementation and sodium-retaining steroids, were identical with the latter. Coincident with the appearance of cardiac failure, all seven patients had a decrease in sodium requirements. Adequate control of the adrenal disease was subsequently possible with elimination of mineralocorticoid support in one of the six who had initially required this therapy and a reduction in dosage in the other five. In all seven, dietary sodium supplements were no longer required. In three patients with severe failure, sodium restriction was imposed and diuretics were added, although the latter therapy has required close monitoring to avoid sodium depletion.