Biomedical subjects
G L Simon
Publications and source records attributed to G L Simon.
Prevalence of cardiac abnormalities in human immunodeficiency virus infection.
The prevalence of cardiac abnormalities in the spectrum of human immunodeficiency virus (HIV) infection is unknown. Sixty consecutive HIV-infected patients were studied using echocardiograms, electrocardiograms (50 patients) and ambulatory electrocardiographic monitoring (43 patients). Group A (25 patients) were seropositive but pre-AIDS, whereas group B (35 patients) had AIDS and included 24 with an active opportunistic infection (group B1) and 11 without it (group B2). Abnormalities were identified in 32 of 60 patients (53%) and were more frequent in group B (23 of 35, 66%) than in group A (9 of 25, 36%, p less than 0.05) but independent of active opportunistic infection (15 of 24, 62%, in group B1 vs 8 of 11, 73%, in group B2). Echocardiographic abnormalities were identified in 21 of 60 patients (35%), including 7 of 25 (28%) in group A vs 14 of 35 (40%) in group B (difference not significant), and 7 of 24 (29%) in group B1 vs 7 of 11 (64%) in group B2 (difference not significant). Those patients with an absolute CD4 lymphocyte count less than or equal to 100/mm3 had a higher prevalence of echocardiographic abnormalities (12 of 22) than those with CD4 counts greater than 100/mm3 (1 of 14, p less than 0.01). Left ventricular dilation or hypokinesis was identified in 14 of 60 patients (23%), including 4 of 25 (16%) in group A and 10 of 35 (29%) in group B. Electrocardiographic abnormalities were seen in 22 of 50 patients (44%) including 5 of 18 (28%) in group A and 17 of 32 (53%) in group B (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
Immune modulation by aspirin during experimental rhinovirus colds.
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Modulation of thymosin alpha 1 and thymosin beta 4 levels and peripheral blood mononuclear cell subsets during experimental rhinovirus colds.
Cellular immune response to localized upper respiratory viral infection was studied in two groups of healthy volunteers infected with an unnumbered rhinovirus serotype (Hanks). In the first group of 18 volunteers, serum levels of thymosin alpha 1 rose on day 5 following rhinovirus challenge. This observation was confirmed in a second group of 20 normal volunteers inoculated with the same rhinovirus strain; there was a slight increase in thymosin alpha 1 levels on day 3 and a significant rise on day 5 (p less than .001). There was also a significant rise in serum thymosin beta 4 levels on day 5 (p less than .001). Serum cortisol rose in parallel with thymosin alpha 1 on day 5 after rhinovirus inoculation, but there was no direct relationship between individual changes in cortisol and thymosin alpha 1 levels. Enumeration of peripheral blood mononuclear cell subpopulations during rhinovirus infection revealed a significant increase in total lymphocytes on day 5 (p less than .01), but not on day 3. The rise in total lymphocyte count was attributable to an increase in T lymphocytes (CD3+) (p less than .05), cytotoxic/suppressor (CD8+) cells (p less than .01) and natural killer (CD16+ cells) (p less than .05). This is the first report of thymic hormone modulation by a virus, and suggests that local rhinovirus infection of the upper respiratory tract has systemic effects and induces cellular immune responses.
Effect of lithium carbonate in HIV-infected patients with immune dysfunction.
Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of less than 300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients.
Corneal ulcers in house staff: are risk factors identifiable?
Thirty-six incoming house officers and 20 incoming third-year medical students had conjunctival cultures taken before and after hospital exposure. The groups were divided evenly between contact-lens and noncontact-lens wearers. A decrease in incidence of positive conjunctival cultures was observed after hospital exposure. Within this group, a lower incidence of positive cultures was observed in contact-lens wearers compared with noncontact-lens wearers. The clinical records of corneal ulcer patients during a three-year period from October 1982 through October 1985 were also reviewed. Significant associated risk factors were identified, the largest of which was contact-lens wear.
Clinical, immunological, and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex.
10 patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or lymphadenopathy syndrome (LAS) were given 200-250 mg ampligen, a mismatched double-stranded (ds) RNA with in-vitro antiviral activity against human immunodeficiency virus (HIV), twice a week for up to 18 weeks, without side-effects or toxicity. In all 9 patients who were positive for HIV RNA in peripheral blood mononuclear cells before therapy, levels became undetectable between days 10 and 40 of the start of therapy. 6 of the 7 patients with ARC or LAS also showed a progressive reduction in HIV load as measured by co-culture assays. All 10 patients had augmentation of delayed-type hypersensitivity skin reactions. Other changes noted during ampligen therapy included an increase in or maintenance of numbers of helper-inducer T lymphocytes, improvements in HIV-related symptoms, rises in titre of neutralising antibodies against HIV, and restoration of proper functioning of the natural lymphocyte antiviral dsRNA-dependent (2'-5'-oligoadenylate/RNA-ase L) pathway. Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication.
Prolonged antiviral activity of D-penicillamine in human immunodeficiency virus-infected homosexual men.
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In vitro effects of thymosin and lithium on lymphoproliferative responses of normal donors and HIV seropositive male homosexuals with AIDS-related complex.
The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P less than 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P less than 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P less than 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed.
Candida vertebral osteomyelitis: report of three cases and a review of the literature.
We have recently treated three patients with Candida vertebral osteomyelitis. In each patient there was at least one characteristic prodromal condition, including trauma, multiple antibiotics following bowel surgery, and acute nonlymphocytic leukemia. All patients were treated successfully with amphotericin B. Based on our findings and a review of the literature, we would recommend a 1.0-1.2 gm total dosage of amphotericin B. Alternative therapeutic choices such as 5FC and/or ketoconazole, under specific clinical conditions, have been successfully employed. However, cure can best be confirmed by post-treatment biopsy.
Increased dose requirements of vancomycin in a pregnant patient with endocarditis.
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The human intestinal microflora.
The major host defense mechanisms against bacterial overgrowth in the small bowel are the normal propulsive activity of the bowel itself and gastric acid secretion. Microbial interactions are a major factor in regulating the indigenous bacterial flora. Studies of the bacterial enzymes of the gut suggest that changes in diet may lead to marked changes in the colonic flora. Antibiotics affect the composition of the colonic microflora. The microflora also influence the degradation of mucin, the conversion of urobilin to urobilinogen, of cholesterol to coprostanol, and the production of short chain fatty acids. Current interests are focused on the bacterial flora of tropical sprue, the role of bacteria in colorectal cancer, and the involvement of intestinal microflora in the enterohepatic circulation of sex steroid hormones.
Peptococcaceae bacteremia.
Bacteremia with Peptococcaceae is an uncommon clinical manifestation of infection with this family of microorganisms. A 20-month review of 12 patients with bacteremic infections due to anaerobic gram-positive cocci revealed that obstetrical patients during the peripartum period constitute the group at greatest risk for the development of such infections. Eight of the 12 patients were young women hospitalized on the obstetrical service. Seven patients had postpartum endometritis and one patient had chorioamnionitis. The remaining four patients include a single patient each with pylephlebitis and microabscesses of the liver, ascending cholangitis, thoracic empyema, and necrotizing soft-tissue infection. Bacteriologic identification of the microorganisms revealed the following: Peptostreptococcus micros (5 patients), Peptostreptococcus asaccharolyticus (5 patients), Peptostreptococcus magnus (1 patient), and Peptococcus species (1 patient). Eleven of the 12 patients received appropriate antibiotic therapy. All patients did well and there were no major sequelae.
Subacute pulmonary mucormycosis.
This report describes two patients with subacute pulmonary mucormycosis who died of pulmonary hemorrhage. Both patients had diabetes mellitus, but neither patient had the typical fulminant illness associated with this infection. The subacute progressive illness seen in these patients is unusual and suggests the need for aggressive diagnostic and therapeutic measures in patients who are at risk for this infection.
Treatment of silastic catheter-induced central vein septic thrombophlebitis.
Two patients with surgically implanted right atrial silastic catheters for home hyperalimentation developed central vein septic thrombophlebitis. Initial treatment including removal of the catheter and antibiotic therapy was unsuccessful and both patients had persistent fever and bacteremia. A clinical and microbiologic response occurred when anticoagulation therapy with heparin was added to the treatment regimen. Although a surgical approach has been emphasized in patients with peripheral vein suppurative thrombophlebitis, anticoagulation therapy may be a useful alternative in the treatment of patients with central vein infection.
Hemophilus influenzae septic arthritis in adults. A report of four cases and a review of the literature.
The clinical and diagnostic features of 29 adult patients with H. influenzae septic arthritis are reviewed. Twelve men and 17 women ranging in age from 22 to 82 years developed the infection. H. influenzae septic arthritis is an acute, febrile disease with a mean duration of symptoms before diagnosis of 4 days. Fifteen patients had monoarticular arthritis, 6 with an infected knee. Polyarticular involvement, with a range of 2 to 9 joints, was diagnosed in 14 patients. Nineteen patients had concurrent extraarticular sites of infection, including meningitis, pneumonia, pharyngitis, sinusitis, conjunctivitis, and cellulitis. Twenty-two of 29 patients had predisposing factors for infection, including ethanolism, trauma, rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, splenectomy, multiple myeloma, lymphoma, gout, and acquired common variable hypogammaglobulinemia. Characteristic synovial fluid findings included purulent, greenish fluid, elevated WBC count, and gram-negative pleomorphic microorganisms. Treatment for these patients included antibiotic therapy, most often ampicillin and chloramphenicol, and joint drainage by repeated arthrocentesis or arthrotomy. A favorable outcome was reported in 25 of 29 patients. Hemophilus influenzae septic arthritis should be suspected in adults who are immunocompromised and have a concurrent extraarticular source of infection.
Treatment of HTLV-III/LAV-infected patients with D-penicillamine.
13 asymptomatic, HTLV-III/LAV-infected male homosexuals with generalized lymphadenopathy were treated with oral D-penicillamine. All patients had depressed T4/T8 ratios and 12 had impaired T-cell function. An escalating dose schedule was employed over 2-6 weeks with doses from 0.5 to 2 g/day. Generalized skin rashes developed in 4 patients which required discontinuation of therapy in one patient. Two patients developed mild transient elevations of hepatocellular enzymes. Reversible decreases in lymph node size, absolute lymphocyte counts, and T-cell lymphoproliferative responses were observed in the majority of patients without change in baseline T4/T8 ratios. All 10 patients treated for at least 2 weeks exhibited evidence for suppression of HTLV-III/LAV replication; complete inhibition of virus expression was seen in 60% of patients treated for 6 weeks. Three of the patients treated for 6 weeks remained culture negative for at least 6 weeks after stopping the drug. D-Penicillamine appears to be an effective drug for suppressing HTLV-III/LAV expression in vivo. Its potential role in the treatment of patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) will require further evaluation.
Phase I/II trial of thymosin fraction 5 and thymosin alpha one in HTLV-III seropositive subjects.
Forty-two male homosexuals and/or hemophiliacs with depressed helper/suppressor T-cell ratios were treated with one of three different doses of thymosin fraction 5 (TF5, 30, 60, and 120 mg), or a single dose of thymosin Alpha One (TA1, 600 micrograms), by daily subcutaneous (SQ) administration for 10 weeks, followed twice weekly for 4 weeks. No major toxicity was noted for any of the preparations tested, although three subjects treated with TF5 had to discontinue therapy because of severe local skin reactions. Of the doses and preparations tested, only 60 mg TF5 was capable of significantly improving (p less than 0.02) mean T-cell lymphoproliferative responses to alloantigens (MLR) for six HTLV-III seropositive subjects who were abnormal prior to therapy. Peripheral blood lymphocytes from subjects treated with 60 mg TF5 also exhibited a transient restoration of mean mitogen-induced interleukin-2 (IL-2) production to normal. No effects were observed with any of the four treatment regimens on absolute helper T-cell numbers, NK activity, antibody titers to HTLV-III, or in the expression of a variety of surrogate markers for acquired immunodeficiency syndrome (AIDS). Four of the six seropositive subjects treated with 60 mg TF5 exhibited a return to depressed baseline MLR, after switching to twice weekly injections. With a median follow-up time of 20 months, six cases of AIDS developed. However, none of the five subjects whose MLR improved following treatment progressed to AIDS. We recommend daily subcutaneous (SQ) administration of 60 mg (40 mg/m2) TF5 for use in combined modality trials, along with drugs capable of suppressing replication of HTLV-III.