James J. Marx

Myocardial magnesium: relation to laboratory and clinical variables in patients undergoing cardiac surgery.

Magnesium concentration was measured in the right atrial appendage of 100 patients undergoing cardiac surgery and associations with serum and mononuclear blood cell magnesium, other laboratory values and patient clinical variables were studied. In addition, magnesium was measured in the right atrial appendage and left ventricular free wall in 23 autopsy subjects to determine whether there was a proportional relation between right atrial appendage and left ventricular free wall magnesium. The mean left ventricular free wall/right atrial appendage magnesium ratio was 2.13 +/- 0.39 (r = 0.67, p = 0.0009). In the group with cardiac surgery, the right atrial appendage magnesium concentration correlated inversely with age (r = -0.54, p = 0.001). The mean right atrial appendage magnesium concentration (micrograms/g wet weight tissue) was lower in patients with postoperative cardiac arrhythmia than in those without arrhythmia (103 +/- 13 versus 111 +/- 10, p = 0.009) and in diabetic than in nondiabetic patients (103 +/- 13 versus 109 +/- 12, p = 0.02). The right atrial appendage magnesium concentration also tended to be lower in patients receiving potassium/magnesium-losing diuretics, although this difference did not achieve statistical significance (105 +/- 14 versus 109 +/- 11, p = 0.16). Right atrial appendage magnesium concentration correlated positively with serum creatinine concentration (r = 0.31, p = 0.002) and negatively with serum calcium concentration (r = -0.29, p = 0.013). Serum magnesium did not correlate with right atrial appendage or mononuclear blood cell magnesium concentration or clinical variables. There was a statistically significant correlation between mononuclear blood cell and right atrial appendage magnesium concentrations in some subgroups of patients.

Farmer's lung disease among farmers with precipitating antibodies to the thermophilic actinomycetes: A clinical and immunologic study☆

Farmers were evaluated for the presence of farmers lung disease by serologic methods and by clinical histories. From a large farming population screened serologically, 40 of 92 farmers with precipitating antibodies to the thermophilic actinomycetes consented to be evaluated for clinical evidence of farmers lung disease. Each subject completed a standardized questionnaire which was reviewd by a trained observer. On the basis of the questionnaire and an indepth clinical history, the subjects were grouped into those farmers who had a history of farmers lung disease (38%), those with no history (50%), or a doubtful group (12%). When these groups were compared for radiologic changes, pulmonary function abnormalities, and immune function, no differences were discernible. None of the parameters tested were useful in predicting which farmer would develop clinical farmers lung disease. The parameters tested did not provide reliable criteria for differentiating those patients who present without acute symptoms but relate a history of recurrent pulmonary illnesses associated with moldy forage.

Comparison of the enzyme-linked immunosorbent assay and double immunodiffusion test for the detection and quantitation of antibodies in farmer's lung disease

Abstract An ELISA for the detection of antibodies to the thermophilic actinomycetes associated with farmers lung disease (FLD) has been described and compared with the standard double immunodiffusion (DID) assay. Parallel determinations of antibody were made with both test systems on sera from 10I0 patients being tested for FLD, as well as on sera from 133 additional subjects previously diagnosed with FLD or assessed as antibody-positive farmers. The ELISA was more sensitive than DID in detecting antibody to the panel of antigens used and also in detecting patients with symptons consistent with FLD. The ELISA was also useful in quantitating antibody in previously diagnosed FLD. When compared with farmers with antibody to the thermophilic actinomycetes and no clinical illness, FLD patients had a higher mean titer as a group, which was not statistically significant.

Multi-drug resistance in chronic lymphocytic leukemia

We evaluated 45 chronic lymphocyte leukemia (CLL) patients for the presence of multi-drug resistance (MDR) by the ex vivo techniques: 1) a functional assay utilizing doxorubicin (dox) retention with modulation; 2) a cytotoxicity assay (MTT) with modulation; 3) and four monoclonal antibodies. Ex vivo tests were correlated with disease stage and prior treatment, and were repeated as patients became resistant to alkylating agents, fludarabine and VAD chemotherapy (infusion of vincristine, dox, and oral dexamethasone). The majority of patients (64.4%) were in early stage and were untreated (62.2%). P-glycoprotein (p-gp 170) was detected most frequently by the monoclonal antibody MRK-16 (48%) and by functional modulation of dox retention by PSC-833 (40.6%) and by functional modulation of the MTT assay with vincristine (0.29) and dox (0.39) with PSC-833 at 1.0 microg/mL. Functional modulation of dox retention with PSC-833 was significantly associated with stage, but not with either the MTT assay or any of the monoclonal antibodies. None of the tests correlated with prior chlorambucil treatment. Correlation of dox retention with the monoclonal antibodies was mild to moderate and became stronger following chlorambucil treatment. Three patients who became resistant to VAD were found to express p-gp 170. We conclude that MDR can frequently be detected in patients with CLL. Furthermore, the expression of p-gp 170 increases with advancing stage, but not prior alkylating agent therapy. The functional expression of p-gp 170 increases with advancing stage and prior treatment and correlates well with monoclonal antibody detection (especially MRK-16). Patients who become resistant to VAD more frequently express p-gp 170 by a variety of techniques. PSC-833 is a more potent modulator of MDR than cyclosporin-A (CsA) ex vivo, and correlates better with stage of disease.

Frequency and clinical significance of Lyme seropositivity in patients with isolated optic neuritis

We evaluated antibody reactivity against Borrelia burgdorferi in 20 consecutive patients with newly diagnosed isolated optic neuritis who resided in a region endemic for Lyme disease. Four (20%) patients had positive serology. All three patients who had follow‐up serologies showed rising convalescent levels of Borrelia‐specific IgM. One patient refused lumbar puncture, one had normal CSF constituents except for an elevated Lyme antibody index, and two had CSF lymphocytic pleocytosis that remained unexplained after extensive evaluations for causes other than Lyme disease. We treated both patients who had CSF pleocytosis with intravenous ceftriaxone; the pleocytosis and optic nerve function improved. The other two patients received oral antibiotics and showed excellent recovery of visual acuity. We believe that serologic testing for Lyme disease is warranted for individuals with optic neuritis who reside in an endemic region, and patients with rising convalescent antibody levels or unexplained CSF pleocytosis should receive antibiotic treatment for Lyme disease. NEUROLOGY 1991;41:706‐711

Hyperimmunoglobulin E syndrome: response to transfer factor and ascorbic acid therapy.

Abstract This report presents the case history of a 29-year-old man with hyperimmunoglobulin E syndrome and the successful treatment with transfer factor and ascorbic acid. The patient presented with a marked defect in the ability of his lymphocytes to respond to mitogens, in skin test response to DNCB challenge and other recall antigens, and a variety of in vitro granulocyte function defects. The presence of a serum inhibitor to lymphocyte and granulocyte function was found. This individual had multiple episodes of mucocutaneous candidiasis and staphylococcal infections. Clinical improvement was evident after transfer factor and ascorbic acid treatment. Many of the in vitro functions also returned to normal.

The 12-lead electrocardiogram of “healthy” ambulatory subjects with positive lyme immunoserology☆

Abstract First described as a distinct clinical entity by Steere et al 1 in 1977, Lyme disease is now known to result from human infection with the spirochete Borrelia burgdorferi , an organism predominantly transmitted by Ixodes ticks. 2 Serologic testing for the presence of antibodies to B. burgdorferi , although imperfect, remains the single best, widely available, laboratory method to demonstrate exposure to the offending organism. 3 The most frequently reported cardiac manifestation of early (stage II) Lyme disease consists of variable degrees of atrioventricular block, including complete heart block. These conduction abnormalities have been documented by 12-lead electrocardiography and invasive electrophysiologic testing. 4,5 Despite advances in characterizing the acute expressions of this spirochetal infection in patients with definite disease, little has been learned regarding the significance of previous subclinical infection, specifically a “positive” Lyme test in an untreated asymptomatic person in an endemic area, with no history of clinically apparent Lyme disease. The aim of this study was to identify any electrocardiographic abnormalities that may be attributable to exposure to the Lyme spirochete in “healthy” seropositive subjects in a Lyme disease endemic area.

Acquired angioedema, autoimmune hemolytic anemia, and lymphoma: Resolution after therapy

Abstract We describe the association of lymphoblastic lymphoma, autoimmune hemolytic anemia, and acquired angioedema in a patient whose decreased levels of C1 inhibitor, C4, and CH 50 and elevated reticulocyte counts returned to normal after removal of a lymphomatous spleen and chemotherapy. The hemolytic anemia, angioedema, and lymphoma have not recurred over a 3-year period following therapy. We compare this patient to other similar reported cases and suggest a possible mechanism for this association.

The Bactericidal Defect of Neutrophil Function with Lithium Therapy

Lithium has been promoted for the treatment of granulocytopenia and as an adjuvant for cancer chemotherapy (Jacob and Herbert, 1974; Gupta et al., 1975; Greco, 1976; Greco and Brereton, 1977; Charron et al., 1977; Tisman and Wu, 1977; Catane et al., 1977; Stein et al., 1977). In preliminary studies of 8 normal volunteers we found a significant bactericidal defect of the granulocytes when studied after 1 week of lithium therapy. We also assessed lymphocyte subpopulations, function, and cell mediated immunity both in vivo and in vitro and could find no defect of lymphocyte function except for a reduction in the response of the lymphocytes to PPD antigen. The rational for the use of lithium is to decrease the incidence of infection in patients who have granulocytopenia. With such defects demonstrated in normals after short term doses, granulocyte and lymphocyte functions were studied in patients on long term lithium therapy.

The treatment of older adult patients with acute myeloid leukemia by triple infusion chemotherapy.

Adult patients (≥56 years old) with acute myeloid leukemia (AML) received induction therapy consisting of daunoruhicin (60 mg/m2). etoposide (80 mg/m2), and cytarahine (200 mg/ m2) daily for 5 days by continuous i.v. infusion (120 hours). The initial protocol was modified so that patients who were not hypoplastic after the tirst cycle of chemotherapy received a second cycle of treatment, utilizing 30 mg/m2 of daunorubicin/24 hours for 5 days plus etoposide and cytarahine as used in the first cycle. Two courses of consolidation with etoposide and cytarahine at the same dose and schedule were given. Patients were then maintained on cytarahine monthly. Twelve of 29 previously untreated patients (41%) achieved complete remission (CR). Excluding patients with secondary AMI., 48% of all patients (11/23) achieved CR. including 56% ≥ 70 years old. The median duration of CR was 41 weeks and median survival of CR patients was 54 weeks. Six of 13 patients (46%) with relapsed AML achieved CR. Toxicity in these older adult patients has been mild. Two patients (8%) had severe mucositis and one had severe (bloody) diarrhea. Most patients developed a mild transient asymptomatic rash. Triple infusion chemotherapy (TIC) may be as effective as other chemotherapy regimens for AML in older adults and has acceptable toxicity.