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Biomedical subjects

H F Ross

Publications and source records attributed to H F Ross.

At least 19 recordsLinked to original sources
PubMed2001

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure.

The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

Aged↗
PubMed2000

A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease.

OBJECTIVE: To compare the incidence of dementia in PD with that of a control group without PD, and to assess the relationship between dementia and other features of PD. METHODS: The authors recruited 83 patients with PD and 50 controls, all without dementia at initial assessment, and assessed them at regular intervals over a maximum period of 122 months. Dementia was diagnosed according to objective criteria, and included a judgment by researchers masked to subject group and to variables putatively associated with dementia. RESULTS: Seventeen patients fulfilled dementia criteria; no controls did so. The cumulative proportion of PD patients becoming demented by 112 months was 0.38 (95% CI 0.20 to 0.55), or 42.6 cases per 1000 years of observation. Univariate analyses showed that incident dementia in patients with PD was associated with older age at entry into the study, greater severity of neurologic symptoms, longer duration of PD, greater disability, and male sex. The association of age at onset of PD with incident dementia was of only borderline significance. Multivariate analysis found that age at entry into the study and severity of motor symptoms were significant predictors of dementia but duration of PD and age at onset of PD were not. CONCLUSIONS: Dementia in PD is likely to reflect interaction of the neuropathology of the basal ganglia and age-related pathology. The findings do not support the division of PD into early and late-onset cases.

Age of Onset↗
PubMed2000

Tooth slice organ culture for cytotoxicity assessment of dental materials.

The purpose of this work was to develop a tooth slice organ culture method to assess the response of the cells of the dental pulp to commonly used dental materials and products. Wistar rat tooth slices were grown in culture for two and ten days in the presence of dental materials. After culture, the tooth tissues were processed and the responses of the pulpal cells were analysed histomorphometrically. Cytotoxic cell destruction was observed following the direct application of test materials to tooth slices (n = 298) after 10 days in culture (MANOVA, P = 0.0001), whilst the restoration of prepared deep dentine cavities (n = 30), with test products, did not result in a significant amount of pulpal injury (MANOVA, P = 0.287). In rank order of causing pulpal injury, the test materials from the most to the least cell destructive, was; Salicylic acid. Calcium hydroxide, Kalzinol zinc oxide eugenol, high-mercury Amalgam, Prime & Bond, Dycal, Barium sulphate, Hypocal, Scotchbond, Calasept, Life and One-step. Tooth slice organ culture, provided a cytotoxicity screening method for dental materials, bearing a closer physiological resemblance to the clinical situation than cell culture screening methods. Tooth slice culturing may have the potential to replace some types of in vivo animal experimentation, as there is a clear need to reduce this form of testing.

Animals↗
PubMed2000

The influence of sample dimensions on hydroxyl ion release from calcium hydroxide products.

The purpose of this study was to compare the rate of hydroxyl ion release from commercially available setting and non-setting calcium hydroxide products. The rate of hydroxyl ion release is important, as this has been suggested to be the main factor in the therapeutic activity of these products. In total, hydroxyl ion release was measured from 1104 samples of Dycal, Life, Calasept and Hypocal in solution using in vitro titration. The rate of hydroxyl ion release was measured for up to 14 days, using two sizes of sample surface area. The dimensions of the exposed sample surface area was found to be an important physical constraint to the hydroxyl ion release from non-setting calcium hydroxide products, whereas this was not found to be the case with setting products. The range in hydroxide activity between products was found to be 298%. In rank order of hydroxide ion release, from the most to the least active was: Hypocal, Calasept, Life and Dycal. The differences in the rate of hydroxyl ion release from these products may have some implications for their clinical applications. It is suggested that in cases where the oral healing responses have been poorer than expected, the size and seal of prepared cavities could have negatively influenced the therapeutic release of hydroxyl ions from non-setting calcium hydroxide products.

Analysis of Variance↗
PubMed2000

Nitric oxide and cardiac autonomic control in humans.

Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23+/-5 years), we measured heart rate variability and baroreflex sensitivity during inhibition of endogenous NO production with N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg per hour) and during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases from baseline (Delta) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison to an equipressor dose of the control vasoconstrictor phenylephrine (12 to 42 microg/kg per hour): Deltaroot mean square of successive RR interval differences (DeltaRMSSD)=23+/-32 versus 51+/-48 ms (P<0.002); Deltapercentage of successive RR interval differences >50 ms (DeltapNN50)=5+/-15% versus 14+/-12% (P<0.05); and DeltaHF normalized power=-2+/-7 versus 9+/-8 normalized units (P<0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/-15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The change in cross-spectral alpha-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.

Adolescent↗
PubMed1999

Use of opposing reflex stimuli and heart rate variability to examine the effects of lipophilic and hydrophilic beta-blockers on human cardiac vagal control.

Evidence from animal studies suggests that beta-blockers can act within the central nervous system to increase cardiac vagal motoneuron activity. We have attempted to determine whether such an effect is evident in healthy humans, by examining the effects of lipophilic and hydrophilic agents on heart rate variability and cardiac vagal reflexes. A total of 20 healthy volunteers took part in the study. Autonomic studies were performed after 72 h of treatment with placebo, atenolol or metoprolol in a blinded cross-over design. ECG recordings were taken at rest and during mental and orthostatic stress. Heart rate variability was measured in the time and frequency domains. The effects on heart rate of two opposing cardiac vagal reflexes were examined. Trigeminal stimulation causing vagal stimulation, and isometric forearm muscle contraction ('muscle heart reflex') causing vagal inhibition, were performed alone and simultaneously. At rest, during mental stress and during trigeminal stimulation, beta-blocker therapy was associated with significantly increased high-frequency beat-to-beat heart rate variability when compared with placebo. There were no significant differences in effects on heart rate or heart rate variability between atenolol and metoprolol. Analysis of the muscle heart reflex, alone and with simultaneous trigeminal stimulation, showed that the magnitude of the R-R interval response was significantly greater after beta-blocker therapy compared with placebo, but the effects of atenolol and metoprolol were equivalent. beta-Blocker therapy increased cardiac vagal activity, as shown by measures of high-frequency heart rate variability and reflex studies. Lipophilic and hydrophilic beta-blockers appeared to be equally efficacious in increasing the cardiac vagal modulation of heart rate.

Adolescent↗
PubMed1998

The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus.

Tst, the gene for toxic shock syndrome toxin-1 (TSST-1), is part of a 15.2 kb genetic element in Staphylococcus aureus that is absent in TSST-1-negative strains. The prototype, in RN4282, is flanked by a 17 nucleotide direct repeat and contains genes for a second possible superantigen toxin, a Dichelobacter nodosus VapE homologue and a putative integrase. It is readily transferred to a recA recipient, and it always inserts into a unique chromosomal copy of the 17 nucleotide sequence in the same orientation. It is excised and circularized by staphylococcal phages phi13 and 80alpha and replicates during the growth of the latter, which transduces it at very high frequency. Because of its site and orientation specificity and because it lacks other identifiable phage-like genes, we consider it to be a pathogenicity island (PI) rather than a transposon or a defective phage. The tst element in RN4282, near tyrB, is designated SaPI1. That in RN3984 in the trp region is only partially homologous to SaPI1 and is excised by phage 80 but not by 80alpha. It is designated SaPI2. These PIs are the first in any gram-positive species and the first for which mobility has been demonstrated. Their mobility may be responsible for the spread of TSST-1 production among S. aureus strains.

Amino Acid Sequence↗
PubMed1998

A central gamma-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam.

1. Animal studies show that cardiac vagal tone can be modified by gamma-aminobutyric acid neurons acting at several sites in the central nervous system. The present study has attempted to determine whether similar control exists in humans by using midazolam, a benzodiazepine. Benzodiazepines exert their main actions on the central nervous system by interacting co-operatively at the gamma-aminobutyric acid receptor. 2. Twenty patients took part in the study before undergoing cardiac catheterization. After resting for 20 min in a semi-supine position on a couch, ECG, blood pressure and respiration were recorded for 5-min periods with either controlled (fixed) or free respiration. During this time a baroreceptor sensitivity test was conducted. 3. Doses of 1 mg and 5 mg of midazolam were administered intravenously. 4. Five-minute segments of data, before and after midazolam, were subjected to power spectral and time-domain analysis. 5. Midazolam caused a decrease in the high-frequency and an increase in the low-frequency components of the power spectral density plot, and in addition reduced the mean R-R interval and R-R variability expressed as the interquartile difference, and pNN50. There were no significant changes in the sensitivity of the baroreflex or in the systolic, diastolic and average blood pressures. 6. This decrease in variability of heart period, particularly at a controlled respiratory frequency, strongly suggests that cardiac vagal tone in man can be regulated by gamma-aminobutyric acid neurons.

Blood Pressure↗
PubMed1997

Is human skeletal muscle capillary supply modelled according to fibre size or fibre type?

Analysis of muscle supply usually relies on estimating either the numerical capillary to fibre ratio or capillary density. Both indices are scale dependent, i.e. they vary with fibre size. We have examined the use of an alternative approach based on the anatomical supply area of individual capillaries, which allows the calculation of a local capillary to fibre ration or density based on area, rather than number of fibres. The results suggest that, in human skeletal muscle, capillary supply is primarily scaled according to fibre size, and is relatively independent of fibre type.

Adult↗
PubMed1995

The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus.

The synthesis of virulence factors and other exoproteins in Staphylococcus aureus is controlled by the global regulator, agr. Expression of secreted proteins is up-regulated in the postexponential growth phase, whereas expression of surface proteins is down-regulated by agr. The agr locus consists of two divergent operons, transcribed from neighboring but non-overlapping promoters, P2 and P3. The P2 operon sequence, reported here, contains 4 open reading frames, agrA, C, D, and B, of which A and C appear to encode proteins of a classical 2-component signal transduction pathway. The P3 operon specifies a 0.5 kb transcript, RNA III, which is the actual effector of the agr response, and, incidentally, encodes the agr-regulated peptide delta-hemolysin. Transcriptional fusions have shown that both P2 and P3 are agr sensitive (function in an agr+ but not in an agr- background) and deletion analysis has shown that all four of the P2 ORFs are involved; agrA and agrC seem to be absolutely required for the transcriptional activation of the agr locus, whereas agrB and agrD seem to be partially required. Since transcription of P2 requires P2 operon products, the P2 operon is autocatalytic, and is thus admirably suited to the need for rapid production of exoproteins at a time when overall growth is coming to a halt.

Amino Acid Sequence↗
PubMed1995

An improved procedure for assessing ABR latency in young subjects based on a new normative data set.

Auditory brainstem response (ABR) latencies in normal young and very young subjects are longer than in mature subjects. Use of adult norms in the assessment of young subjects may therefore result in the erroneous reporting of abnormalities in subjects who are in no way impaired. In this study a new normative data set was established by measuring ABR absolute and interpeak latencies in 374 subjects in different age groups with normal ABR and no risk factor for hearing impairment or neurological abnormality. Double exponential functions were fitted to a number of latency measures derived from the data and from those functions a table of correction values was computed. The variability in the measurements of the children is greater than that of the adults. Procedures are proposed which enable the assessment of abnormality of ABR latencies to be made for all subjects regardless of age.

Adolescent↗
PubMed1995

Anti-epithelial (anti-A549) antibodies: their nature, specificity and relevance to transplantation.

Several studies have addressed the possible importance of anti-epithelial cell antibodies in kidney transplantation using the A549 cell line as an in vitro model. In this paper we report our results using for the first time an enzyme-linked immunosorbent assay (ELISA) to detect the anti-A549 cell antibodies. Sera from 129 kidney transplant patients were tested for IgM anti-epithelial cell antibodies directed against the A549 cell line prior to transplantation; only three sera were positive (2.3%). 101 of these patients were then followed-up post-transplantation; sera were collected routinely at 2, 6 and 12 weeks and at the time of rejection episodes. All samples were also tested for cytomegalovirus (CMV) IgM antibodies. Sixteen patients developed anti-A549 IgM antibodies, and there was no correlation with acute graft rejection. Anti-epithelial antibodies showed no binding to sections of normal kidney or biopsies of rejected kidneys. Eleven patients were positive for anti-CMV IgM antibodies. In nine cases both IgM anti-A549 and IgM anti-CMV antibodies were found, which was a highly significant association (p < 0.001). Analysis of A549 cellular proteins by immunoblotting gave evidence for the presence of CMV polypeptides in the cell lysate. Electron-microscopic examination of A549 cell preparations revealed intracellular particles which were compatible in size with CMV. Polymerase chain reaction analysis confirmed the presence of a specific CMV DNA sequence in A549 cells of several batches from different sources. Our data strongly suggest that the A549 cell line used in several published reports is infected with CMV and that in the majority of cases the anti-A549 'anti-epithelial' antibodies found in renal transplant patients are anti-CMV antibodies.

Adolescent↗
PubMed1994

Agonist and antagonist EMG activation during isometric torque development at the elbow in spastic hemiparesis.

Voluntary isometric step contractions of the elbow flexor and extensor muscles were studied in a group of patients with paresis arising as the result of unilateral cerebral lesion and in a control group of normal subjects. For each subject the maximum isometric torque in flexion and extension was obtained, along with a series of graduated torque steps up to this maximum, in order to perform a regression analysis between torque developed and the associated agonist and antagonist EMG. This relationship proved to be linear in all normal subjects and in all but the most paretic spastic patients. If the patients were grouped according to their ability to make discrete large angle flexion and extension movements at the elbow, a clear correspondence was seen between increasing movement disability and the degree of paresis. No significant differences were found in the torque/EMG relationship of spastic patients when either elbow extensors or flexors were acting as the agonist in a contraction. Similarly, no evidence of exaggerated antagonist co-activation was found. It is concluded that, in the upper arm muscles, hemiparesis following stroke cannot, under isometric conditions, be attributed to hyperactivity of antagonist muscles.

Adult↗
PubMed1993

Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule.

The production of most toxins and other exoproteins in Staphylococcus aureus is controlled globally by a complex polycistronic regulatory locus, agr. Secretory proteins are up-regulated by agr whereas surface proteins are down-regulated. agr contains two divergent promoters, one of which directs the synthesis of a 514 nucleotide (nt) transcript, RNAIII. In this report, we show that the cloned RNAIII determinant restores both positive and negative regulatory functions of agr to an agr-null strain and that the RNA itself, rather than any protein, is the effector molecule. RNAIII acts primarily on the initiation of transcription and, secondarily in some cases, at the level of translation. In these cases, translation and transcription are regulated independently. RNAIII probably regulates translation directly by interacting with target gene transcripts and transcription indirectly by means of intermediary protein factors.

Base Sequence↗
PubMed1993

The limitations of the tendon jerk as a marker of pathological stretch reflex activity in human spasticity.

The motor disorders associated with human spasticity arise, partly from a pathological increase in the excitability of muscle stretch reflexes. In clinical practice, reflex excitability is commonly assessed by grading the reflex response to a blow delivered to the tendon of a muscle. This is a much simpler response than the complex patterns of activity which may be elicited following muscle stretch caused by active or passive movement. Changes in the biceps brachii tendon jerk response have been followed over the first year after stroke in a group of hemiparetic patients and compared with changes in short and medium latency reflex responses elicited by imposed elbow flexion of initially relaxed spastic muscle and with the development of the late reflex responses which contribute to spastic hypertonia. A progressive increase in tendon jerk responses occurred over the first year following stroke, whereas reflex responses to imposed displacement, in particular the late reflex responses contributing to muscle hypertonia, reached their peak excitability one to three months after stroke, with a subsequent reduction in activity. The tendon jerk reflex therefore provides an incomplete picture of the pathological changes in the reflex responses in spasticity.

Adult↗
PubMed1991

Biomechanical changes at the ankle joint after stroke.

The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the "healthy" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed.

Ankle Joint↗
PubMed1989

Quantifying capillary distribution in four dimensions.

Analysis of spatial distribution using numerical (O-D) distribution is limited to global estimates, while linear (1-D) separation of capillaries may be used to describe unrealistic spatial patterns. Intramuscular diffusion is best viewed as an integration of all distances between surrounding capillaries, or area (2-D) of influence for individual vessels. True planar analysis also accommodates other forms of heterogeneity, and may be extrapolated to give the volume (3-D) of tissue supplied by capillaries. Temporal (4-D) heterogeneity in functional spacing may then be quantified.

Animals↗