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Biomedical subjects

J D Allan

Publications and source records attributed to J D Allan.

At least 55 records · Page 3Linked to original sources

Beta-lactam/aminoglycoside combinations: interactions and their mechanisms.

Combinations of beta-lactams with aminoglycosides are widely used in the therapy of infections. There are a number of theoretic advantages to using such combinations. Indeed, combinations of beta-lactams and aminoglycosides usually result in synergism or indifference and very rarely in antagonism. The mechanisms of synergism, resistance to synergism, and antagonism have been studied extensively in enterococci; further studies are necessary to define such mechanisms in other organisms.

Aminoglycosides↗

Human T-lymphotropic virus type III infection in previously immunocompromised hosts.

The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection. Development of unusual infectious diseases in patients with neoplasms and other underlying immune deficiency disorders should lead to consideration of HTLV-III infection. Surveillance data should be obtained on these patients to accurately define the scope of HTLV-III infection.

Acquired Immunodeficiency Syndrome↗

Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome.

We conducted virus-isolation studies on 56 specimens from the nervous system of 45 patients in order to determine whether human T-cell lymphotropic virus Type III (HTLV-III) is directly involved in the pathogenesis of the neurologic disorders frequently encountered in the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. We recovered HTLV-III from at least one specimen from 24 of 33 patients with AIDS-related neurologic syndromes. In one patient, HTLV-III was isolated from the cerebrospinal fluid during acute aseptic meningitis associated with HTLV-III seroconversion. HTLV-III was also isolated from cerebrospinal fluid from six of seven patients with AIDS or its related complex and unexplained chronic meningitis. In addition, of 16 patients with AIDS-related dementia, 10 had positive cultures for HTLV-III in cerebrospinal fluid, brain tissue, or both. Furthermore, we cultured HTLV-III from the spinal cord of a patient with myelopathy and from the sural nerve of a patient with peripheral neuropathy. These findings suggest that HTLV-III is neurotropic, is capable of causing acute meningitis, is responsible for AIDS-related chronic meningitis and dementia, and may be the cause of the spinal-cord degeneration and peripheral neuropathy in AIDS and AIDS-related complex.

Acquired Immunodeficiency Syndrome↗

Antimicrobial combinations in the therapy of infections due to gram-negative bacilli.

Antimicrobial combinations are used most frequently to provide broad-spectrum coverage; however, they are also frequently employed to enhance antimicrobial activity (synergism). Although there is extensive in vitro documentation of synergism for many antibiotic combinations, a clear advantage for these combinations has been difficult to demonstrate in clinical studies. Several types of combinations have been useful in clinical medicine and frequently result in synergism. These include combinations of a cell wall-active agent with an aminoglycosidic aminocyclitol, combinations of a beta-lactamase inhibitor with a beta-lactam, and combinations of agents that inhibit sequential steps in a metabolic pathway. Given its spectrum of activity, aztreonam will often be used with clindamycin or a beta-lactam antibiotic. Combinations of beta-lactams may be synergistic via several mechanisms. However, these combinations also exhibit significant potential for antagonism when used against gram-negative bacilli and, therefore, require careful evaluation prior to clinical use.

Aminoglycosides↗

Comparative in vitro activities of cefpiramide and apalcillin individually and in combination.

The in vitro activities of cefpiramide and apalcillin were compared with those of other third-generation cephalosporins and extended-spectrum penicillins against over 1,000 clinical bacterial isolates. The activity of cefpiramide against Pseudomonas aeruginosa was comparable to those of piperacillin and cefoperazone, inhibiting 90% of strains at concentrations less than or equal to 16.0 micrograms/ml. This drug was also active against a broad range of gram-negative organisms but was generally less active than many of the other cephalosporins tested against members of the family Enterobacteriaceae. The activity of cefpiramide against gram-positive organisms was comparable to that of cefoperazone. Apalcillin, along with ceftazidime, was the most active agent tested against P. aeruginosa and Acinetobacter calcoaceticus subsp. anitratus, inhibiting 90% of these strains at concentrations less than or equal to 8 micrograms/ml. Against other gram-negative and gram-positive organisms, its activity was similar to that of piperacillin. The activities of both cefpiramide and apalcillin were significantly reduced by the presence of several plasmid-mediated beta-lactamases in a series of otherwise isogenic strains of P. aeruginosa in comparison with their activities against a parent strain which lacks these enzymes. Many strains of Enterobacter cloacae were synergistically inhibited by the combination of gentamicin with either cefpiramide (5 of 10 strains) or apalcillin (6 of 10 strains). Most strains of P. aeruginosa were synergistically inhibited by the combination of gentamicin with either cefpiramide (8 of 10 strains) or apalcillin (10 of 10 strains). However, cefoxitin antagonized the activity of both cefpiramide and apalcillin against most of these same strains.

Ampicillin↗

Seroepidemiology of human T-lymphotropic virus type III among homosexual men with the acquired immunodeficiency syndrome or generalized lymphadenopathy and among asymptomatic controls in Boston.

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p less than 0.001). Six patients with generalized lymphadenopathy developed the acquired immunodeficiency syndrome over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic controls had had sexual contact with a man with the syndrome; receptive anal intercourse in this group was associated with seropositivity for HTLV-III. These data suggest that persistent generalized lymphadenopathy and the acquired immunodeficiency syndrome are part of a clinical spectrum of HTLV-III infection and that most high-risk homosexual men in some regions of the United States have not yet been infected with this virus.

Acquired Immunodeficiency Syndrome↗

Cell-mediated immunity in patients with cystic fibrosis.

Leucocytes from 26 patients with cystic fibrosis (CF) and 18 healthy controls were investigated by migration inhibition induced by a variety of antigens. In patients with CF cell-mediated immunity was found to human lung and pancreatic tissue extracts as well as to Aspergillus fumigatus, Pseudomonas aeruginosa, and food antigens but not to brain, heart, or kidney. Those patients with the severest form of the disease had the greatest impairment of cell-mediated immunity, but this impairment could be reversed by steroid treatment. Cell-mediated cytotoxicity may also be concerned in the pathogenesis of CF.

Adolescent↗

Immune complexes in cystic fibrosis.

Circulating immune complexes were detected in serum and sputum of patients with cystic fibrosis (C.F.). There were extensive deposits of immunoglobulins and complement immune complexes in several of the C.F. organs, especially the respiratory and gastrointestinal tracts, but not in the kidneys. Significant concentrations of IgG and of complement complexes could be eluted from the lungs of the C.F. patients but not from those of controls. Studies involving immunoabsorption, autoradiography, and molecular sieving through Sephadex G-200 columns identified both bovine serum albumin and staphylococcal alpha-haemolysin as two of the antigens present in the immune complexes. The sedimentation constant of the immune complexes was about 8S to 11S. The clinical significance of these immune complexes and the wide variety of antibodies detected in C.F. patients are discussed.

Adsorption↗

Immediate hypersensitivity in patients with cystic fibrosis.

Twenty-three out of thirty patients with cystic fibrosis gave strong immediate skin hypersensitivity reaction to a wide variety of allergens. Seventy-five per cent of these had a markedly elevated serum IgE concentration whereas those patients who had negative Type 1 immediate skin reactions also had normal levels of serum IgE. The sputum of those patients with immediate skin reactivity also had positive precipitins to a variety of antigens.

Allergens↗