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Biomedical subjects

R Blair

Publications and source records attributed to R Blair.

At least 19 recordsLinked to original sources
PubMed1996

Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.

BACKGROUND: Preclinical findings suggest that intra-arterial gene transfer of a plasmid which encodes for vascular endothelial growth factor (VEGF) can improve blood supply to the ischaemic limb. We have used the method in a patient. METHODS: Our patient was the eighth in a dose-ranging series. She was aged 71 with an ischaemic right leg. We administered 2,000 micrograms human plasmid phVEGF165 that was applied to the hydrogel polymer coating of an angioplasty balloon. By inflating the balloon, plasmid DNA was transferred to the distal popliteal artery. FINDINGS: Digital subtraction angiography 4 weeks after gene therapy showed an increase in collateral vessels at the knee, mid-tibial, and ankle levels, which persisted at a 12-week view. Intra-arterial doppler-flow studies showed increased resting and maximum flows (by 82% and 72%, respectively). Three spider angiomas developed on the right foot/ankle about a week after gene transfer; one lesion was excised and revealed proliferative endothelium, the other two regressed. The patient developed oedema in her right leg, which was treated successfully. INTERPRETATION: Administration of endothelial cell mitogens promotes angiogenesis in patients with limb ischaemia.

Aged↗
PubMed1996

Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome.

Nerve root enhancement of the cauda equina occurs in Guillain-Barré syndrome (GBS), but the frequency, diagnostic value, and meaning of this finding is unknown. We prospectively obtained gadolinium-enhanced lumbosacral spine MRIs in 24 consecutive patients with acute GBS and blindly rated nerve root enhancement as absent, mild, or prominent. The MRIs were obtained 13 days, mean, after onset of symptoms (range 2 to 42 days). Twenty of 24 patients had cauda equina nerve root enhancement, which was mild in 6 and prominent in 14. Eighteen of 19 with "typical" GBS had enhancement, compared with 2 of 5 with a variant presentation. Sixty percent of patients with prominent enhancement had severe back or leg pain in contrast to 10% of patients with mild or no enhancement. The GBS disability grade (0 to 5 scale) was higher in patients with prominent enhancement, and significantly fewer patients with prominent nerve root enhancement could walk independently by 2 months. There was no relationship between nerve root enhancement and the timing of the MRI, CSF protein, any of several EMG abnormalities, duration of hospitalization, mean disability grade at 2 months, or the time required for patients to improve to grade 2. In two patients, the EMGs at 11 and 20 days, respectively, were normal except for slightly prolonged F-responses and neurogenic recruitment, but there were prominent nerve root enhancement and an elevated CSF protein. Enhancement of the cauda equina nerve roots with gadolinium on lumbosacral MRI is 83% sensitive of acute GBS and was present in 95% of typical cases. This finding may be useful when electrophysiologic abnormalities are equivocal. In addition, conspicuous nerve root enhancement correlates with pain, GBS disability grade, and duration of recovery.

Acute Disease↗
PubMed1995

Possible involvement of the HLA-DQB1 gene in susceptibility and resistance to human dilated cardiomyopathy.

There is evidence that autoimmunity plays a role in the pathogenesis of dilated cardiomyopathy and that susceptibility to the disease is related to products of human leukocyte antigens (HLA) class II genes. We compared the distribution of HLA-DQA1 and -DQB1 alleles and haplotypes in 44 normal controls and 34 patients with idiopathic dilated cardiomyopathy patients. The distribution of two DQA1-DQB1 haplotypes (*0102-*0604 and *0102-*0501) were more frequent in the patients. Histidine at position 30 of the HLA-DQB1 gene was associated with disease (62% of patients compared to 36% of controls), whereas homozygosity for leucine at position 26 was more frequent in controls (36% vs 18% of patients). There was no correlation between HLA-DQA1-DQB1 haplotypes and the presence of anti-beta-receptor antibodies. These results suggest that the HLA-DQB1 gene is involved in the pathogenesis of human dilated cardiomyopathy.

Adult↗
PubMed1994

Clearance of Histoplasma capsulatum variety capsulatum antigen is useful for monitoring treatment of experimental histoplasmosis.

We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum antigen concentration in tissues and blood provided a marker for antifungal effect of itraconazole in a nonlethal murine model of histoplasmosis. Treatment with itraconazole (Sporanox), in cyclodextrin, was evaluated in a pulmonary model of histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of infection. All mice were sacrificed on day 15 of infection. Blood, spleen, and lung tissues were removed for culture and quantification of antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267. Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The cyclodextrin formulation of itraconazole (Sporanox) demonstrated antifungal activity in experimental histoplasmosis. Antigen detection was a useful marker for antifungal effect.

Animals↗
PubMed1994

The Histoplasma capsulatum antigen assay in disseminated histoplasmosis in children.

Progressive disseminated histoplasmosis is often fatal without treatment and requires rapid and accurate laboratory diagnosis. Radioimmunoassay for Histoplasma capsulatum var. capsulatum antigen has been established as a sensitive and accurate diagnostic technique for disseminated histoplasmosis in adults; this study examines the radioimmunoassay in children. The clinical and laboratory records of 26 patients 18 years old or younger in whom H. capsulatum antigen was detected in urine by radioimmunoassay and at least one other positive corroborative standard test were evaluated. Twenty-two (85%) had disseminated disease, and 4 (15%) had self-limited pulmonary disease. Positive corroborative tests included serologic tests in 17 of 22 (77%) patients tested, tissue stains in 5 of 9 (56%) and fungal cultures in 16 of 24 (67%). Patients with disseminated histoplasmosis had a greater degree of antigenuria than those with self-limited infection. In 20 patients with progressive disease treated with amphotericin B, antigen levels declined, and the decrease in antigenuria correlated with clinical improvement. The radioimmunoassay for H. capsulatum antigen in urine is an important test in the diagnosis of disseminated histoplasmosis and is useful for assessing the efficacy of treatment. The presence of urinary antigen is strong evidence for progressive disease that requires treatment.

Adolescent↗
PubMed1993

Local immunity in lung-associated lymph nodes in a murine model of pulmonary histoplasmosis.

Local immunity against acute pulmonary histoplasmosis was studied in the lung-associated lymph nodes of normal nonimmune mice infected intratracheally with live Histoplasma capsulatum yeasts. The phenotypes and distribution of cells in lung-associated lymph nodes and spleens were determined by flow cytometry. In addition, the immune responsiveness of these cells was evaluated by in vitro blastogenesis. Anti-H. capsulatum antibodies in serum and H. capsulatum antigen in tissue were measured by immunoassays. Cellular immune responses were greater in the lymph nodes than in the spleens. In lymph nodes 7 days after infection, a marked increase in the number of B lymphocytes caused the percentage to rise to 43%, compared with 26% in controls, and it remained elevated throughout the course of infection. A CD3+ cell that did not express CD4 or CD8 increased in number until it constituted 21% of lymph node cells, compared with 5% in controls, by day 14. The numbers of CD4+ and CD8+ T lymphocytes were modestly increased from days 7 to 35, but their percentages dropped because of the greater numbers of B lymphocytes and CD3+4-8- cells. Macrophages consistently constituted 2 to 3% of lymph node cells during the study. In spleens 7 days after infection, the percentage of macrophages in infected mice rose to 21%, compared with 9% in controls, but the total spleen cell number did not increase until day 14, when all cell subsets were nearly double in number. The in vitro blastogenic response of lymph node cells to H. capsulatum peaked at day 7, but spleen cell response was minimal during the course of infection. Histoplasma-specific serum immunoglobulin G antibodies reached peak levels by day 21 and remained high to the end of the study. In contrast, levels of antigen-specific immunoglobulin M antibodies were very low. These data suggest that antigen-specific immune responses occur in lung-associated lymph nodes and that this draining lymph node response may be an important component in host defense against Histoplasma lung infection.

Acute Disease↗
PubMed1993

Effects of lighting pattern and dietary tryptophan supplementation on growth and mortality in broilers.

The effect of lighting pattern and supplementation of the diet with Trp on growth and mortality of male broiler chickens was evaluated in three experiments using 2,392, 2,608, and 2,400 chickens, respectively. There were two lighting treatments, either a constant 23 h of continuous light/24-h period or an increasing photoperiod lighting system, i.e., 0 to 3 days, 23 h light (L):1 h dark (D); 4 to 14 days, 6L:18D; 15 to 21 days, 10L:14D; 22 to 28 days, 14L:10D; 29 to 35 days, 18L:6D; 36 to 42 days, 23L:1D. The design was a completely randomized 2 x 2 factorial, with four replicates per treatment. In the first two experiments, a starter diet with or without .2% supplemental L-Trp (feed grade) was fed from 0 to 3 wk of age and a finisher diet with or without .2% supplemental Trp was fed from 3 to 6 wk of age. In the third experiment, the level of supplemental Trp was .4% in the starter and finisher diet. Birds raised on the increasing light pattern consumed less feed during the first 3 wk, were lighter in weight at 3 wk, and had lower feed:gain ratios (P < .001) than their counterparts on constant light. By market age (6 wk) they had similar body weight but feed intake was significantly (P < .05) lower in all experiments, and feed:gain ratio was significantly lower in these birds in Experiment 3 (P < .05) than in their counterparts on constant light.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Behavioral responses of broiler chickens to handling: effects of dietary tryptophan and two lighting regimens.

In three 2 x 2 factorial experiments, effects of added dietary Trp (0 or .2%, Experiments 1 and 2; 0 or .4%, Experiment 3) and two lighting regimens [1) constant 23-h photoperiod (23H); or 2) increasing photoperiod (INC)] on behavioral responses of broilers to handling were assessed. In Week 6 of Experiment 1, and Weeks 3 and 6 of Experiments 2 and 3, 32 chickens from each treatment were picked up and held by both legs for 30 s, carried for 60 s, and induced into tonic immobility (TI). In all experiments, chickens reared under INC were more likely to flap when carried, and flapped longer, than chickens reared under 23H (P < .01). In Experiments 2 and 3, INC chickens were more likely to curl the body ventrally when handled and were more susceptible to TI induction than 23H chickens (P < .05). The duration of TI was shorter on INC than 23H in Experiment 2 (P < .05), and longer in Experiment 3 (P < .001). Dietary Trp supplementation resulted in a lower flapping duration and higher incidence of body curling in Experiment 2 (P < .05), and a shorter TI duration in Experiment 3 (P < .05). Flapping, body curling, and TI responses of chickens varied between handlers (P < .05). Vocalization and flapping rates were lower, and flapping incidence and duration of flapping and TI higher, in Week 6 than in Week 3 (P < .05). Chickens reared under INC may be at greater risk of injury during preslaughter handling than chickens reared under 23H.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.

PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Tolerance of growing pigs for dietary vitamin A, with special reference to bone integrity.

Weanling crossbred pigs (144) of 8 kg initial weight were fed to 90 kg on diets containing graded levels of vitamin A representing 0, 1, 5, 10, 50 and 100 times the NRC (1988) estimated requirement. No clinical signs of deficiency or toxicity were recorded although plasma and liver retinol levels were affected by treatment. Histopathological examination indicated a high incidence of lesions in the cartilage of the distal femur and ulna, but they were not related to treatment. There was some evidence that excessive vitamin A levels in the diet significantly reduced the uronic acid concentration in joint cartilage, indicating a reduced concentration of proteoglycans. However no relationship was established between dietary vitamin A level and the incidence of clinical osteochondrosis. The results suggest that the allowable range of vitamin A set out in the Canadian feeds regulations is appropriate for practical pig production.

Animals↗
PubMed1991

Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels.

OBJECTIVE: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study using stored specimens. SETTING: A referral center and several private hospitals. PATIENTS: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. MEASUREMENTS: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. MAIN OUTCOME MEASURE: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. MAIN RESULTS: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; CI, 0.03% to 6.6%) obtained on 56 occasions (1.8%; CI, 0.04% to 9.6%) from controls (specificity, 98.2%; CI, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; CI, 10.9% to 69.2%) but in 0 of 9 control patients (CI, 0% to 28.3%). CONCLUSION: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗
PubMed1991

Redox modulation of N-methyl-D-aspartate-stimulated neurotransmitter release from rat brain slices.

Rat brain cortical slices released tritiated norepinephrine ([3H]NA) during a 2-min stimulation with N-methyl-D-aspartate (NMDA). Dithiothreitol (DTT; 0.1-5 mM), present for 6 min prior to stimulation, dose-dependently increased the release of [3H]NA from cortical slices stimulated with a maximally effective concentration of NMDA (500 microM). Similar results were observed for [3H]NA release from hippocampal slices and tritiated and endogenous dopamine release from striatal slices. DTT treatment also markedly shifted the dose-response curve of NMDA to the left. Cortical slices released approximately the same amount of [3H]NA with 10 microM NMDA following DTT treatment (about 5%) as non-DTT-treated control slices did with 500 microM NMDA. The effects of DTT were fully reversed by subsequent treatment with 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB; 0.5 mM). DTT treatment did not significantly alter the ability of magnesium (1.3 mM) or the polyamine antagonist arcaine to block the NMDA-stimulated release of [3H]NA. In contrast, DTT treatment significantly attenuated the antagonist effects of the competitive glycine antagonist, 7-chlorokynurenic acid, and the competitive NMDA antagonist, 2-aminophosphonopentanoic acid. These results suggest that oxidation and reduction of disulfide bonds located within the NMDA receptor complex might regulate the activation of the NMDA receptor. This could have important consequences in vivo if endogenous oxidizing/reducing systems are found to have similar effects on NMDA-stimulated responses.

Animals↗
PubMed1991

Lack of an effect of taurine supplementation on the incidence of sudden death syndrome in male broiler chicks.

Two experiments were conducted to study the effect of taurine supplementation on growth and the incidence of Sudden Death Syndrome (SDS) in male broiler chickens. The 4,650 birds were day-old male broiler chickens raised in floor pens to 9 wk of age. In Experiment 1, the birds received diets containing 0, 250, 500, or 1,000 mg taurine/kg. In Experiment 2, the treatments were no added taurine, 500 mg taurine/kg feed, 1,000 mg taurine/kg feed, 250 mg taurine/L water, and 500 mg taurine/L water. Taurine supplementation did not have any significant influence on growth performance although supplementation of the feed at 250 mg/kg reduced the feed:gain ratio from 1.67 to 1.63 in Experiment 1, which was significant (P less than .05). In general, mortality was unaffected by treatment with a few exceptions: in Experiment 2, SDS deaths were reduced significantly (P less than .01) by supplementation of the feed with 500 mg taurine/kg, and at 3 and 6 wk of age, SDS deaths as a percentage of total deaths were reduced significantly with this treatment. The results are interpreted as suggesting that taurine does not play a major role in the etiology of SDS.

Animal Feed↗
PubMed1991

The effect of taurine transport antagonists on cardiac taurine concentration and the incidence of sudden death syndrome in male broiler chickens.

Two experiments were conducted in which 540 day-old male broiler chickens were raised in heated battery brooders to 4 wk of age. Diets contained taurine antagonists to test effects on cardiac taurine content and the incidence of Sudden Death Syndrome (SDS). In Experiment 1 treatments during Weeks 2 to 4 were A) basal diet; B) basal diet supplemented with .25% guanidinoethyl sulfonate (GES) in Week 2 and 1.5% GES in Weeks 3 and 4; and C) basal diet supplemented with .5% GES in Weeks 2 to 4. The taurine content of heart was significantly reduced (P less than .05) with GES supplementation, but no effects on SDS mortality rates were noted. In Experiment 2 birds received diets containing 0. 2.5, or 5% beta-alanine. Supplementation with this compound decreased cardiac taurine concentration to extremely low levels (P less than .05). No significant effects on SDS mortality rates were noted. The results are interpreted as suggesting that taurine does not play a major role in the etiology of SDS.

Animals↗