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Biomedical subjects

M Gardner

Publications and source records attributed to M Gardner.

At least 91 records · Page 5Linked to original sources

SIV vaccines: current status. The role of the SIV-macaque model in AIDS research.

SIV vaccines made of inactivated whole virus, modified live virus and native and recombinant envelope antigens have protected macaques against experimental infection with low doses of cell-free SIV given systemically. The few vaccinated monkeys that do become infected have tended to live longer than the infected controls. Protection against cell-associated virus has not as yet been tested. The recombinant envelope vaccines now on test have generally not been as effective as the whole virus vaccines. Post-infectious immunotherapy with SIV vaccines has been ineffective. The same whole virus and modified live virus vaccines that protect against systemic infection fail to protect against genital mucosal challenge with cell-free virus. Since sexual transmission is the major route of HIV spread on a global scale, a major effort is now required to develop vaccines in this animal model that induce genital mucosal as well as systemic immunity against infection with both cell-free and cell-associated SIV.

Animals↗

Subclass and molecular form of immunoglobulin A antibodies to Actinobacillus actinomycetemcomitans in juvenile periodontitis.

Patients with juvenile periodontitis frequently have elevated levels of serum immunoglobulin A (IgA) antibodies to antigens of Actinobacillus actinomycetemcomitans. IgA occurs in two subclasses, IgA1 and IgA2, and in monomeric and polymeric forms. Because IgA1 is susceptible to cleavage by IgA1 proteases produced by microorganisms found at mucosal sites and in the gingival crevice, we wished to determine the IgA subclass distribution of antibodies to antigens of A. actinomycetemcomitans. The molecular form was examined because it may indicate the origin of the IgA and because the form differs in acute and chronic infections. There is also evidence that monomeric and polymeric IgA have different biological functions. Serum was taken from patients with juvenile periodontitis before and at intervals during and after initiation of therapy. IgA subclass distribution was determined against a sonic extracts of A. actinomycetemcomitans ATCC 2952a (serotype b) by using monoclonal anti-subclass reagents in an enzyme-linked immunosorbent assay. To determine the molecular form of the antibodies, sera were separated by high-performance liquid chromatography on a size-exclusion column. Fractions were assayed for antibody activity by the enzyme-linked immunosorbent assay, and described above. The results of the subclass analysis of the sera indicated that while both IgA1 and IgA2 antibodies to A. actinomycetemcomitans sonic extract are often found before, during, and after treatment, IgA1 antibodies dominated the response. There was a predominance of monomeric IgA1 antibodies to A. actinomycetemcomitans sonic extracts in most samples before, during, and after treatment. The monomeric form is consistent with what is seen in other chronic infections. The predominance of IgA1 antibodies implies that any protective effects of the IgA response to A. actinomycetemcomitans could be compromised by microbial IgA1 proteases.

Actinobacillus Infections↗

Effect of information organization on recall of medication instructions.

This study compared immediate recall of prescription information when the message content was presented in a highly organized format versus a less-organized approach. Two groups of pharmacy students viewed separate videotapes, which described information for a patient about three fictitious medications. Students were then asked to recall the medications' name, colour, purpose, dosage, duration, side-effects and quantity prescribed. Students who viewed the organized version correctly recalled more information in every category except drug colour. Both groups made more errors in recalling dosage than any other category. Thus, organizing information facilitates recall of medication information.

Adult↗

Neutrophil surface protein markers as indicators of defective chemotaxis in LJP.

Abnormalities of neutrophil function have been highly correlated with severe, early onset periodontal diseases. Nonetheless, the identification of these patients and diagnosis of specific disease states, such as LJP or prepubertal periodontitis, are difficult and costly. In this report, the identification and quantification of neutrophil cell surface markers specific to LJP patients with neutrophil chemotaxis defects are described. GP110 and FMLP receptors were quantified by flow cytometry on neutrophils from LJP patients with neutrophil chemotaxis defects, LJP patients without chemotaxis defects, other patients with primary neutrophil chemotaxis defects, and controls. Results suggest that reduction of GP110 and FMLP receptor on neutrophils is specific for LJP patients who exhibit neutrophil chemotaxis abnormalities.

Adolescent↗

Biological and molecular characterization of human immunodeficiency virus (HIV-1BR) from the brain of a patient with progressive dementia.

HIV-1BR was isolated from the autopsied brain tissue of a 57-year-old man who died of progressive dementing illness. This virus was shown to be HIV-1 by hybridization to HIV-specific DNA probes. The expression of viral proteins as tested by radioimmunoprecipitation assay revealed the presence of HIV-1-specific proteins. HIV-1BR replicated in cultures of CD4+ T-lymphoid cells and induced cytopathic effects in these cells. HIV-1BR also replicated in monocytoid cell lines. The genetic nature of this isolate was determined by molecular cloning and sequencing of the 3'-half of the genome. DNA sequence information established that HIV-1BR is a unique HIV-1 isolate. A stretch of approximately 30 bases in the nef gene of HIV-1BR was found duplicated when compared with the other sequenced HIV-1 genomes. The functional significance of this duplication remains to be determined.

Acquired Immunodeficiency Syndrome↗

A study of the cells in the explanted viable cryopreserved allograft valve.

From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve. Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability. The allograft valve was obtained from coroner's autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death). Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve. A uniform protocol for valve preparation was used during the entire experience. Nine allograft aortic valves have been obtained by eight reoperations (two were for leaflet degeneration) and one autopsy. The time intervals from implantation to explantation were 2 months, 10 months, 20 months, 22 months, 2.2 years, 5 years, 8.3 years, 9.2 years, and 10.8 years. Histologic examination of the leaflet tissue disclosed a variable degree of cellularity, ranging from a highly cellular matrix (9.2 years) to minimal cellularity (20 months). Within the same valve (10 months), one leaflet was completely acellular with a moderate degree of cellularity in the other two leaflets. The competent valve recovered at autopsy (8.2 years) was essentially acellular. Fibroblasts could consistently be cultured from leaflets in which viable cells were seen histologically. Chromosomal analysis of cultured cells from a valve leaflet (9.2 years) that was implanted with a donor and recipient sex mismatch demonstrated persistence of donor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

The viable cryopreserved allograft aortic valve.

One hundred and twenty-four patients underwent aortic valve replacement with a nonviable 4 degrees C refrigerated aortic allograft valve. One hundred and eighty-four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow-up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perforation or rupture whereas no patients in the group with viable valves developed this complication (p less than 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long-term follow-up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.

Actuarial Analysis↗

Molecular characterization of the Akvr-1 restriction gene: a defective endogenous retrovirus-borne gene identical to Fv-4r.

A dominant restriction allele, Akvr-1r, from California wild mice (Mus musculus domesticus) confers resistance to exogenous ecotropic murine leukemia virus (MuLV) infection. The presence of an ecotropic MuLV envelope-related glycoprotein in uninfected virus-resistant cells suggests that viral interference is a possible mechanism for this resistance. We molecularly cloned the ecotropic MuLV envelope-related sequence from the genomic DNA of a wild mouse homozygous for the Akvr-1r locus. The cloned provirus was defective and contained a C-terminal end of the pol gene, a complete envelope gene, and a 3' long terminal repeat. The presence of this provirus was directly correlated with Akvr-1r-mediated virus resistance in cell cultures and hybrid mice. The Akvr-1r provirus restriction map and partial DNA sequence were identical to those of the Fv-4r allele, an ecotropic MuLV resistance locus from Japanese feral mice (M. musculus molossinus), which was previously shown to be allelic with the Akvr-1r gene. The 3' host flanking sequences of Fv-4r and Akvr-1r also had identical restriction maps. These findings indicate that Akvr-1r and Fv-4r are the same gene. It was probably acquired by interbreeding of these feral species in recent times. Conservation of this locus might be favored by the useful function that it performs in protection against ecotropic MuLV infection endemic in both populations of wild mice.

Alleles↗

Hematologic abnormalities in simian acquired immune deficiency syndrome.

Hematologic abnormalities were defined in 31 rhesus monkeys (Macaca mulatta) with simian acquired immune deficiency syndrome (SAIDS). Animals manifested anemia (hypochromic/microcytic), severe neutropenia and progressive lymphopenia, monocytosis and occasional thrombocytopenia. Bone marrow studies showed erythroid hyperplasia with a marked left shift and adequate megakaryocytes. Two animals showed profound hypoplasia of all hematopoietic elements. Most animals were iron deficient, but the course of the anemia suggested additional factors. There was no evidence of immune hemolysis. The pathogenesis of these abnormalities is not clear and will require further study. This reproducible disease will allow studies to elucidate the mechanisms of viral-induced hematologic abnormalities.

Acquired Immunodeficiency Syndrome↗

Long-term survival with the right lower lobe as the only lung tissue.

The case of a patient who underwent left pneumonectomy at 23 years of age is described. When he was 54 years old, he required resection of the right upper and middle lobes. He survived and lived an active life for more than three years with the right lower lobe as his only lung tissue.

Activities of Daily Living↗

Encircling endocardial resection with complete removal of endocardial scar without intraoperative mapping for the ablation of drug-resistant ventricular tachycardia.

Encircling endocardial resection, with complete removal of endocardial scar unguided by intraoperative mapping, was employed in 10 patients with drug-resistant sustained ventricular tachycardia. Reproducible sustained ventricular tachycardia was induced in all patients preoperatively with programmed electrical stimulation. A trial of conventional antiarrhythmics had failed in all 10 patients; seven patients required frequent cardioversion, and three patients required overdrive suppression with temporary transvenous pacing. Encircling endocardial resection was performed in all patients, with complete removal of endocardial scar; partial reimplantation of the mitral apparatus was required in nine patients. Eight patients underwent aneurysmectomy, and the nine patients who required concomitant aorta-coronary bypass received a total of 13 grafts (mean 1.3 grafts per patient). There were no spontaneous postoperative arrhythmias. One patient without postoperative clinical arrhythmias, who had required daily preoperative cardioversion, had inducible ventricular tachycardia with postoperative programmed electrical stimulation, but not after loading with procainamide. Mean follow-up was 17.3 months. Eight patients are alive and well. There were two late deaths. One patient died with recurrent ventricular septal defects 2.5 months following extensive septal encircling endocardial resection, and one patient was readmitted after 4 months with massive pulmonary embolus and right-sided heart failure. This early experience suggests that this procedure, with complete removal of endocardial scar, successfully ablates reentrant ventricular tachycardia. We believe that the procedure will prove to be more effective than localized endocardial resection because the encircling procedure removes all ventricular sites that have the potential to generate reentrant ventricular tachycardia.

Aged↗

Effects of oral amiodarone on left ventricular function in dogs: clinical implications for patients with life-threatening ventricular tachycardia.

Twenty-four mongrel dogs were divided into two equal groups to determine the effects of orally administered amiodarone on left ventricular function. Measurements of left ventricular function included left ventricular contractility as denoted by maximum rate of rise of left ventricular pressure (dP/dtmax), cardiac index (CI), left ventricular stroke work index (LVSWI), and peripheral vascular resistance (PVR). Left ventricular function was measured in 6 of the 12 animals in Group 1 before and after 14 days of amiodarone administered orally; the remaining animals served as controls. The dP/dtmax was reduced from 2,855 to 1,291 mm Hg/sec (p less than 0.01), and LVSWI fell from 1.6 to 0.74 gm-m/beat/kg (p less than 0.05) in the 6 animals given amiodarone. The 12 animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals were given amiodarone orally for 14 days prior to cardiopulmonary bypass and ischemic arrest; the other 6 served as controls. Before cardiopulmonary bypass, the dogs administered amiodarone had significantly greater depression of dP/dtmax (p less than 0.01) and LVSWI (p less than 0.05). Thirty minutes of ischemia produced significant depression of left ventricular function in all animals in Group 2. However, a significantly greater reduction in dP/dtmax and LVSWI occurred in those animals receiving amiodarone. Furthermore, 4 of the 6 dogs receiving amiodarone were unable to sustain sufficient cardiac output following cardiopulmonary bypass to permit long-term survival (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Enhanced gastrointestinal excretion of phenytoin in a patient with Crohn's disease.

A patient with Crohn's disease and generalized seizures who lacked the distal small bowel and ascending colon required 600 mg of intravenous phenytoin daily (11 mg/kg/24 h) to maintain her plasma phenytoin levels in the 12-24 micrograms/ml range. She received no oral phenytoin. Stool volumes ranged from 1,125 to 1,875 ml/24 h, and stool fraction phenytoin levels from 15 to 41 micrograms/ml. Urinary 5-(p-hydroxyphenyl)-5-phenylhydantoin and phenytoin levels in three 24-h samples were sufficient to account for 26, 46, and 57% of the administered drug, compared with the expected 70-90%. This was most likely due to an alteration of the normal cycle of absorption and reexcretion between the intestinal lumen and the blood resulting in net excretion of phenytoin into the bowel.

Adult↗

Encircling endocardial resection for sustained drug-resistant ventricular tachycardia.

Localized endocardial resection guided by intraoperative mapping has been used recently to manage patients with drug-resistant ventricular tachycardia. Although not uniformly successful, this procedure is superior to simple aneurysmectomy. This report describes the authors' early experience with encircling endocardial resection with complete removal of endocardial scar in seven patients with drug-resistant, sustained, ventricular tachycardia, as identified by electrophysiologic studies. Intraoperative mapping was not used. Although no spontaneous clinical arrhythmia occurred after operation, ventricular tachycardia could be induced in one patient, but not after loading with procainamide. This was the only patient who required long-term antiarrhythmic therapy. There were no operative deaths, but one patient died 21/2 months after endocardial resection with recurrent ventricular septal defects and another died after 4 months. Our early experience indicates that encircling endocardial resection effectively eliminates re-entrant ventricular tachycardia and identifies ventricular septal defect as a potential postoperative complication following extensive septal endocardial resection.

Aged↗