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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 541 records · Page 30Linked to original sources
PubMed1990

Tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis.

This study was designed to evaluate the tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis. Serum, peritoneal fluid, bile, gallbladder wall and pancreatic tissue concentrations of cefotaxime in these groups of pigs exceeded the MIC90 for susceptible species of Gram-negative aerobic bacteria. Cefotaxime penetration into pancreatic tissue and peritoneal fluid was increased from 2% to 2.6% and 73% to 89%, respectively, in pigs with pancreatitis in comparison with normal pigs. These increases however, were not statistically significant.

Animals↗
PubMed1990

A longitudinal study of the cultivable subgingival anaerobic bacteria isolated from sheep during the development of broken mouth periodontitis.

In a longitudinal bacteriological study of the cultivable subgingival anaerobic flora isolated from developing broken mouth periodontitis in sheep, samples were taken from five sheep on each of three farms on seven occasions over a period of 2.5 years. Ten different bacterial genera were isolated regularly but with fluctuating frequencies. Bacteroides and Fusobacterium organisms accounted for nearly 70% of the isolates. The Bacteroides and Fusobacterium isolates studied in detail from one farm were identified to species level. The fusobacteria comprised F. nucleatum-like organisms (68.6%). F. necrophorum (29.6%) and F. naviforme (1.8%). The Bacteroides spp. were divided into 11 main groups and included black-pigmented species similar to B. asaccharolyticus and B. gingivalis. On the farm studied in detail, the sheep could be allocated to two groups according to progression of periodontal disease. Most of the B. gingivalis-like isolates were from sheep with actively progressing disease, indicating that this organism may play a role in periodontal destruction in sheep.

Animals↗
PubMed1990

Levels of cytochrome P-450-mediated aryl hydrocarbon hydroxylase (AHH) are higher in differentiated than in germinative cutaneous keratinocytes.

Induction of microsomal aryl hydrocarbon hydroxylase and cytochrome P-450 was observed in epidermal cells obtained from the skin of newborn rats exposed to benz(a)anthracene by topical exposure and in submerged cultures exposed to the procarcinogen in vitro. The level of aryl hydrocarbon hydroxylase activity was increased 2.5-fold in vivo and six- to sevenfold in vitro when the measurements were made on the entire epidermis or the entire culture, respectively. However, separate measurement on germinative (basal) and on differentiated cells revealed that AHH was sevenfold higher in differentiated cells as compared with basal cells in the skin of both unexposed animals and animals exposed in vivo. Similar results were obtained in cultured cells exposed in vitro. Immunocytochemical staining of sections of skin from animals exposed to benz(a)anthracene in vivo with a monoclonal antibody generated against cytochrome P-450c showed a higher binding of the antibody in lower spinous cells than in basal cells in the epidermis. Although more stained cells were observed in exposed cultures than in untreated cultures, the antibody, which inhibits at least 85% of the hydroxylase activity in the skin, inhibited only 6%-16% of the activity in culture. These observations support the interpretations that a) differentiated keratinocytes have a higher capacity in the metabolic activation of PAH than do germinative cells, although both types of cell are susceptible to induction of cytochrome P-450 by exposure to BA, and b) the cytochrome P-450 induced by exposure of epidermis to benz(a)anthracene in vivo exhibits some differences from the one induced upon exposure of keratinocytes to this procarcinogen in vitro.

Animals↗
PubMed1990

Evaluation of the effect of azapropazone on neutrophil migration in anaesthetized swine using a multichamber blister suction technique.

1. The purpose of this study was to determine the in vivo inhibitory efficacy of azapropazone on neutrophil migration. The effects of azapropazone given at a dose of 100 mg kg-1 i.v. every 2 h on the neutrophil migration into skin inflammation sites (blister fluid) as well as into an autologous serum (+/- chemoattractant) placed above the blister surface (2nd chamber) were determined. 2. Azapropazone treatment schedule maintained blood levels at 70-100 micrograms ml-1 throughout the time course (360 min) of the experiment. 3. Azapropazone significantly inhibited (48 +/- 6%) neutrophil migration into the blister fluid (as evident from the decrease in myeloperoxidase activity). 4. Azapropazone significantly inhibited the neutrophil migration into the autologous serum either with (65 +/- 5%) or (35 +/- 6%) without the chemoattractant, formyl-methionyl-leucyl-phenylalanine (FMLP). The chemoattractant, FMLP, markedly increased neutrophil migration into the autologous serum by approximately 1.5 to 2 times the non-FMLP treated group. Azapropazone was more efficacious in inhibiting the neutrophil migration in the presence of FMLP than in its absence. 5. We conclude that azapropazone is an effective inhibitor of neutrophil migration into topically inflamed sites in anaesthetized swine.

Anesthesia↗
PubMed1990

Evaluation of the effect of azapropazone on neutrophil migration in regional myocardial ischaemia/reperfusion injury in rabbits.

1. The purpose of the present study was to determine the myocardial cytoprotective efficacy of azapropazone (AZA) and its potential site of action on neutrophil infiltration into reperfused/ischaemic myocardium with or without in vivo activation of neutrophils in rabbits. 2. AZA, 100 mg kg-1, was administered i.v. 10 min after occlusion of the left circumflex (LCX) artery in rabbits with and without pretreatment with phorbol myristate acetate ester (PMA). The LCX occlusion was then released at 10 min after AZA administration. Haemodynamic parameters (heart rate, LV pressure, mean arterial blood pressure and dp/dt) were monitored throughout the experiment. After 60 min reperfusion, the area at risk was delineated and the heart was then excised and divided into epi- and endocardial pieces for analysis of myeloperoxidase activity. 3. AZA inhibited neutrophil infiltration into the reperfused/ischaemic rabbit myocardium with and without PMA treatment. The inhibition of neutrophil infiltration was more apparent in the epicardium than in the endocardium. Additionally, AZA inhibited to a similar extent the in vivo PMA-stimulated neutrophil migration into the epicardium and endocardium area at risk. AZA had no significant effect on the haemodynamic parameters as compared to control. 4. AZA administered in an anaesthetized rabbit model of LCX occlusion/reperfusion resulted in the reduction of infarct size. 5. It is concluded that AZA has significant inhibitory effects on neutrophil migration which might contribute to its myocardial cytoprotective effect.

Animals↗
PubMed1990

Screening for subclinical sleep-disordered breathing.

We evaluated self-administered questionnaires and short sleep studies in screening for sleep-disordered breathing (SDB) in 40 hypertensive men ages 36-66 unselected for symptoms. Each subject completed a questionnaire including questions on sleep-related symptoms and underwent overnight polysomnography in which we evaluated the apnea-hypopnea index (AHI) and the percentage of time during which arterial O2 saturation was less than 90% (T90). The first 90 min of overnight study was evaluated separately, and 10 subjects with an AHI greater than or equal to 10 also underwent late afternoon nap study. By overnight polysomnography, 48% of the cohort had an AHI greater than or equal to 10, and 35% had a T90 greater than or equal to 10%. Using linear regression, we found no features of the symptom questionnaire that strongly predicted AHI. Only self-reported snoring and baseline arterial Po2 significantly predicted T90. The AHI and T90 were not significantly correlated. Considering an AHI greater than or equal to 10 in the overnight study as "abnormal" and an AHI greater than or equal to 10 on the short study as a "positive" test, the specificity of the AHI in the first 90 min was 100% (21/21), and the sensitivity was 42% (8/19). The sensitivity of the nap study was 60% (6/10). We conclude that in a cohort unselected for symptoms, the ability of self-administered questionnaires to predict SDB was low; short studies were only moderately sensitive for detecting an AHI greater than or equal to 10, and the AHI was not a major determinant of nocturnal desaturation.

Adult↗
PubMed1990

Blunt cardiac injury: is this diagnosis necessary?

The diagnosis of blunt cardiac injury in traumatized patients is problematic and the implications of such a diagnosis are not clear. Although cardiac selective creatine kinase (CK-MB) assays and electrocardiograms (EKG) are the most widely available laboratory investigations, they often correlate poorly with diagnoses made on clinical grounds, or by other laboratory methods. We therefore retrospectively studied the Montreal General Hospital experience with 342 consecutive blunt trauma patients admitted to our surgical intensive care/trauma unit. Using clinical criteria, cardiac injury was diagnosed in 44 patients (13%). Twenty-seven of these patients (61%) developed arrythmias or cardiogenic hypotension, half of which required treatment. Heart injuries contributed to six of the 12 deaths in this group. Many of the patients maintained normal CK-MB levels and/or had normal admission EKG's despite the clinical diagnosis of cardiac injury. However, using our criteria for CK-MB positivity, there was a strong correlation between CK-MB elevation and the development of cardiac complications, and very high CK-MB levels (greater than 200 mu/L) were associated with a 100% incidence of such complications. Focusing on patients who developed cardiac complications serious enough to require treatment, we found combined CK-MB/EKG positivity in all cases (100% sensitivity). This method also provided a negative predictive value of 100%. We conclude that although blunt cardiac injury is an important source of morbidity and mortality its 'diagnosis' is not the issue. Rather, it is more important to recognize which of these clinically identified 'high-risk' patients will actually develop cardiac complications. We feel our approach will enable clinicians to do this.

Adult↗
PubMed1989

Internal amino acid sequence analysis of the 80 kDa protein kinase C substrate from rat brain: relationship to the 87 kDa substrate from bovine brain.

We have obtained sequence data from five proteolytic peptides totalling 102 amino acid residues of the 80 kDa protein kinase C substrate purified from rat brain. The amino acid sequences of these five peptides were compared with that deduced from a cDNA encoding the 87 kDa protein kinase C substrate from bovine brain. The overall amino acid sequence identity within the regions covered by our peptides is 54%. Two peptides aligned at the C- and N-termini of the bovine protein kinase C substrate with a very high degree of homology (more than 80% identity). Two other peptides exhibited 62% and 46% identity with two regions located in the C-terminal half of the bovine protein. The fifth peptide which contains the sequence PEQPEQPEQ did not reveal any similarity with the bovine protein. Based on the homologies of our experimentally determined sequences, which represent about 30% of the deduced sequence of the bovine protein, we suggest that although these protein kinase C substrates are not identical, they may belong to a family of related proteins.

Amino Acid Sequence↗
PubMed1989

Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease.

Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry.

Alzheimer Disease↗
PubMed1989

'Air hunger' arising from increased PCO2 in mechanically ventilated quadriplegics.

A number of investigators have proposed that the sense of respiratory discomfort accompanying hypercapnia depends on respiratory mechanoreceptors which inform the sensory cortex of reflex increases in breathing. To test this hypothesis, we studied subjects whose respiratory muscles were paralyzed, and who were thus unable to increase breathing in response to hypercapnia. We gradually elevated inspired PCO2 in four tracheostomized quadriplegic subjects supported by constant mechanical ventilation. These subjects reported sensations of 'air hunger' (e.g., "short of breath", "air-starved") when end-tidal PCO2 increased 10 Torr (mean) above their resting levels. In a second experiment we used the forced-choice technique to determine the ability of three of these subjects to detect repeated changes of end-tidal PCO2. Two detected 7 Torr changes, the third detected 11 Torr changes. These data suggest that changes in breathing are not necessary to evoke the sense of 'air hunger'. We conclude that the likely mechanisms are (1) projection of chemoreceptor afferent traffic to the sensory cortex, and (2) projection of corollary discharge from brainstem respiratory centers to the sensory cortex.

Adult↗
PubMed1989

The influence of high-resistance training on glucose tolerance in young and elderly subjects.

Aging is associated with a decrease in glucose tolerance. In younger subjects both high and low intensity forms of exercise have been shown to improve glucose tolerance. The purpose of this investigation was to determine whether or not strength training in elderly subjects would have a positive effect upon glucose and insulin responsiveness following a glucose feeding. The medical history of each subject and an exercise stress test were given prior to the establishment of the two age groups: those individuals with contra-indications for exercise were not tested further. An oral glucose tolerance test, 100 g, was administered to six young (23 +/- 1 year) and 9 elderly (63 +/- 1 year) male subjects before and after 12 weeks of a supervised progressive resistance weight lifting program, which employed Nautilus equipment. All the major muscle groups of the body were exercised and a three set, six-eight repetition, training protocol was followed. Blood samples were taken at 0, 30, 60, 120 and 180 min; after centrifugation (1169 g for 15 min) the serum was frozen for analysis of glucose and insulin. Percent body fat was determined by skin calipers and the Lean Body Mass estimated. The 6 Rep max for the leg press, leg extension and bench press machines were used to determine the strength gains made for the 12 weeks of training. The results show that both the young and elderly subjects had a significant increase (P less than 0.05) in LBM and a significant decrease (P less than 0.05) in percent body fat with training. In the young these changes occurred without a significant change in body weight, whereas the elderly had a significant increase (P less than 0.05) in body weight. In terms of strength, both the young and elderly showed significant gains (P less than 0.05) following training. The training protocol had little effect on the glucose response, but did significantly lower (P less than 0.05) the plasma insulin response to a glucose load. In response to a 100 g oral glucose load insulin declined regardless of age, with the insulin sum of the young and elderly being, 31.8% and 32.6% lower, respectively, after training. Although strength training improved glucose tolerance in both age groups, the response of the elderly subjects was well below that of the young. In conclusion, the data present here demonstrate that 12 weeks of high resistance strength training improved the overall physical fitness level of both the young and elderly participants of this study, but did not affect age related differences.

Adult↗
PubMed1989

Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects.

We observed the response of serum growth hormone (GH) and testosterone (T) to a progressive resistance strength training program. Basal levels (after a 12-h fast) of GH and T were measured in young (23 years) and elderly (63 years) subjects before and after a 12-week training program. The response of GH and T to an acute bout of exercise was also measured. The exercise training, which involved all the major muscle groups, was conducted on Nautilus equipment and required 45-60 min for completion. The subjects completed three sets of lifts with 8-10 Reps/set. Blood was drawn from an anticubital vein, centrifuged (1169 g) for 15 min and the serum frozen for later analysis. The acute exercise blood samples were taken immediately before and after the exercise and at 15 min post-exercise during week 1 and 12. The hormone assay was carried out with radioimmunoassay kits for GH and T. The basal level of GH increased by 44.9% in the young and by only 3% in the elderly but neither change was significant. In response to a single exercise session GH levels in the young went from 0.85 +/- 0.13 to 4.19 +/- 1.45 ng/ml before training and from 1.45 +/- 0.11 to 8.61 +/- 2.55 after training. Each response was significant (P less than 0.05) as were the pre-post differences (P less than 0.001). In the elderly the response was not as great, values increasing from 1.00 +/- 0.09 to 2.92 +/- 0.65 ng/ml before training and from 1.50 +/- 0.06 to 3.43 +/- 0.64 ng/ml after training were recorded. These differences represented significant increases (P less than 0.05) but did not demonstrate pre- to post-changes. Basal levels of T decreased in both groups, but were not significant. The T response to an acute bout of exercise was not significant but did increase in both age groups. In conclusion, the data presented here indicate that strength training can induce growth hormone and testosterone release, regardless of age, but that the elderly response does not equal that of the young.

Adult↗
PubMed1989

Characterization of a broadly expressed human leucocyte surface antigen MEM-43 anchored in membrane through phosphatidylinositol.

A monoclonal antibody MEM-43 was prepared, which recognizes an antigen expressed on all peripheral blood leucocytes, on erythrocytes and several cell lines, but is absent from U937, Nalm-6, Daudi and Raji cell lines. The antigen isolated by immunoaffinity chromatography from several cell lines is an 18,000-25,000 mol. wt glycoprotein. An apparently identical antigen isolated from erythrocytes binds to several lectins and has a 14,000 mol. wt polypeptide backbone, modified by an endoglycosidase F-sensitive carbohydrate moiety. The epitope recognized is reduction-sensitive. The sequence of N-terminal 17 amino acid residues was determined; five out of six N-terminal amino acids are identical to those found at the N-terminus of the mouse lymphocyte surface antigen Ly-6C. The antigen is completely released from the cell surface after treatment with phosphatidylinositol-specific phospholipase C.

Amino Acid Sequence↗
PubMed1989

Interleukin-1 beta and muramyl dipeptide can prevent decreased antibody response associated with sleep deprivation.

A single, brief (8 h) period of sleep deprivation (DEP) was found to suppress secondary antibody response to sheep red blood cells in rats. This decrease could be totally prevented if either interleukin-1 beta (IL-1) or muramyl dipeptide (MDP) was administered at the beginning of the DEP vigil. Twenty-five units of IL-1 or 250 micrograms/kg MDP was found to be immunosuppressive in sleeping rats but, paradoxically, the combination of such doses with DEP alleviated this effect. Increased colonic temperatures associated with antigen and/or adjuvant administration were not related to the differences in antibody levels between sleeping and DEP animals. Activation of hypothalamic dopamine in IL-1-treated rats following DEP suggests that this monoamine transmitter system may participate in the observed protective activity of IL-1. The present findings extend the immune adjuvant effects of both IL-1 and MDP to protection of the host against behaviorally induced immunosuppression.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Nicardipine and hydrochlorothiazide in essential hypertension.

Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.

Adult↗