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Biomedical subjects

S E Smith

Publications and source records attributed to S E Smith.

At least 127 records · Page 7Linked to original sources

The effect of posture on the intraocular pressure and pulsatile ocular blood flow in patients with non-arteritic anterior ischaemic optic neuropathy.

Intraocular pressure (IOP) and pulsatile ocular bloodflow (POBF) have been recorded in 15 patients with unilateral non-arteritic anterior ischaemic optic neuropathy (na-AION) and in 28 healthy subjects of comparable age. Measurements were obtained in both the upright and lying postures with a pneumotonometer linked to a Langham ocular bloodflow system. By comparison with the healthy subjects, patients with na-AION were found to have a significantly greater postural pressure change in IOP (3.9 +/- 0.4 mmHg in the affected eye and 3.6 +/- 0.6 mmHg in the unaffected eye of the patients with na-AION compared to 2.2 +/- 0.4 mmHg in the right eye of the healthy subjects P less than 0.01 and less than 0.05 respectively). There was no significant difference between the IOP in the affected and unaffected eyes of patients with na-AION nor between this group and the healthy subjects in either posture. Pulsatile ocular bloodflow measurements were similar in both groups and in both eyes of the patients with na-AION. In both groups POBF fell significantly on lying down (healthy right eyes -84 +/- 16 ul/min p less than 0.01, na-AION affected eye -84 +/- 24 ul/min p less than 0.01, unaffected eye -83 +/- 26 ul/min p less than 0.001). These figures represent decrements of 19% in all groups. These findings suggest that assumption of the supine posture may be associated with a reduction in the pulsatile component of ocular perfusion. The importance of this in the pathogenesis of na-AION is discussed.

Adult↗

Antenatally detected pelviureteric junction obstruction. Is non-operation safe?

We report follow-up data (minimum of 1 year) on 63 kidneys with antenatally detected pelviureteric junction obstruction, as defined by renographic criteria. The condition was bilateral in 10 patients (i.e. 20 kidneys), 2 patients had unilateral obstruction with contralateral multicystic dysplastic kidneys, and 41 patients had unilateral obstruction with a normal contralateral kidney. In the latter group, 29 (71%) had good function (greater than 40%) at initial assessment. Of the 63 kidneys, 24 (38%) were operated upon following initial assessment, mainly for impaired function. Of 39 patients, initially managed non-operatively, 8 (21%) were operated upon subsequently: 3 for deteriorating function (2 of whom have been reassessed and both have regained their lost function) and 5 for other renographic or ultrasonic indications). Of the original 63 kidneys, 31 (49%) continue to be managed non-operatively; 16 of these (52%) show improving ultrasound appearances, 8 of 17 studied show improved drainage, and all unilateral cases have stable good function. It is concluded that non-operative management of selected cases of antenatally detected pelviureteric junction obstruction is safe.

Female↗

Postural studies in pulsatile ocular blood flow: I. Ocular hypertension and normotension.

Measurements of pulsatile ocular blood flow (POBF) have been recorded in a group of healthy, ocular normotensive volunteers and ocular hypertensive patients recruited from outpatients. Use of a pneumotonometric probe linked to a Langham ocular blood flow system enabled readings of intraocular pressure and its variation with heart rate (ocular pulse) to be taken in erect and supine positions. Pulsatile ocular blood flow was calculated from these values by means of the pressure-volume relationship previously described for living human eyes. Assumption of the supine posture was accompanied by a significant rise in intraocular pressure; in normal eyes (mean, with SEM) (3.1 (0.4) mmHg, p less than 0.0001) and to a greater extent in ocular hypertensive eyes (4.7 (0.6) mmHg, p less than 0.0001). The POBF did not differ significantly between normotensive and ocular hypertensive groups in either the erect or supine postures. In both groups, however, assumption of the supine posture was accompanied by a significant fall in POBF (normals: -121 (21) microliters/min, p less than 0.0001; ocular hypertensives: -75 (16) microliters/min, p less than 0.0002). These reductions in POBF represent decrements of 27.5 (3.0)% and 17.1 (3.8)% respectively. Pulsatile ocular blood flow is reduced in the supine posture, and this may result in tissue hypoxia in subjects at risk of developing glaucoma. A companion paper describes the measurement of POBF in a group of patients with chronic open angle glaucoma treated with topical timolol 0.25%.

Adult↗

Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma.

The pulsatile ocular blood flow (POBF) has been recorded in 15 patients with chronic open angle glaucoma. Measurements were performed during regular treatment with timolol 0.25% eyedrops, two weeks after withdrawal of this treatment, and then a further two weeks after its reinstitution. Readings were taken with subjects in both the erect and supine positions by means of a pneumotonometric probe to measure intraocular pressure (IOP), linked to a Langham ocular blood flow system. Assumption of the supine posture was associated with a significant increase in IOP in all phases of the study. Treatment with timolol lowered the mean IOP in comparison with the untreated phase (-4.4 (SEM 0.6) mmHg, p less than 0.001) but had no effect on the postural change. A significant reduction in POBF was recorded on assumption of the supine posture (-66 (SEM 18) microliters/min, p less than 0.001), representing a mean decrement of 19%. However, there were no significant differences in POBF between treated and untreated phases of the study. Comparison of the values obtained in patients with glaucoma (COAG) after withdrawal of treatment with those in subjects with ocular hypertension revealed that there was no significant difference in intraocular pressure between the two groups. However, both POBF (-68 (SEM 29) microliters/min) and the pulse amplitude of the intraocular pressure (ocular pulse: -0.45 (SEM) 0.14 mmHg) were significantly lower in the COAG patients. Pulsatile ocular blood flow is significantly lower in patients with chronic open angle glaucoma. Furthermore, the POBF and the postural response of these patients is not improved by the use of topical timolol therapy.

Adult↗

Measurement of aqueous cells and flare in normal eyes.

(abstractThe Kowa laser cell flare meter has been recently introduced to quantify the assessment of aqueous cells and flare in vivo by measurement of light scattering from a low power HeNe beam. Computer analysis of this scattered light can distinguish cells (expressed as cell count) from protein (expressed as photon count/ms), and in-vitro work with albumin solutions has shown that the photon count/ms is linearly related to protein concentration. This study of 106 normal eyes (53 subjects) assesses the accuracy and sensitivity of the instrument and the factors affecting the interpretation of its results. Using in-vitro solutions of human albumin we found a highly significant linear correlation (r = 1, p = 0.0001) between photon count and protein concentration. The results show that the instrument has a photon count/ms reproducibility of 8.26% and that there is a within-subject variability in photon count/ms (aqueous flare) of 12.2% in normal eyes. No significant difference in photon count/ms (aqueous flare) was found to exist between right and left eyes (p greater than 0.4), between sexes (p greater than 0.5), or between irides of different colour (p greater than 0.8). There was also no statistically significant variation in photon counts/ms with time of day over the period of measurement (1000-1900 h) (p = 0.4). There was, however, an increase in photon count/ms with age (r = 0.57, p less than 0.001) and a decrease with pupillary dilatation at both 30 and 60 minutes after instillation of tropicamide 1% (p less than 0.05). An occasional cell was found in only 10.4% of normal eyes, and there was no significant increase in the cell counts on mydriasis (p>0.05). These findings indicate that the Kowa laser flare meter is an accurate and sensitive instrument with potential application in the investigation of blood-aqueous barrier.

Adolescent↗

Ocular responses in healthy subjects to topical bunazosin 0.3%--an alpha 1-adrenoceptor antagonist.

The ocular effects of the alpha-adrenoceptor blocking drug bunazosin, administered as eyedrops, have been measured in a placebo-controlled double-blind single-dose study in 15 healthy volunteers. The drug significantly reduced intraocular pressure over 10 hours, and there was no associated change in pulsatile ocular blood flow. Characteristic effects of alpha-adrenoceptor blockade were observed--miosis, ptosis, and conjunctival hyperaemia. The miosis alone persisted for more than 24 hours in nine out of 15 subjects.

Adrenergic alpha-Antagonists↗

Pulsatile ocular blood flow in patients with low tension glaucoma.

Measurements of the intraocular pressure (IOP) pulse and pulsatile ocular blood flow (POBF) have been made in 22 patients with bilateral low tension glaucoma (LTG) and 29 healthy subjects matched as closely as possible for age, refractive error, IOP, systemic pulse pressure, and heart rate. Recordings were made in both the standing and supine positions. The amplitude of the intraocular pressure pulse was significantly lower in patients with LTG (1.2, SEM 0.1 mmHg standing, and 1.3, SEM 0.1 mmHg lying) than in healthy subjects (1.9, SEM 0.1 mmHg standing, and 2.0 SEM 0.1 mmHg lying): p less than 0.001 standing and p less than 0.002 lying. Measurement of POBF also showed a significant reduction between the healthy subjects (428 (31) SEM microliters/min standing and 345 (28) SEM microliters/min lying) and subjects with LTG (301 (27) SEM microliters/min standing and 249 (24) SEM microliters/min lying), p less than 0.005 standing and p less than 0.02 lying. This represents a difference of approximately 30% between the two groups in either posture. A close non-parametric correlation existed between the level of IOP and the POBF (r = 0.75, p less than 0.001 standing, and r = -0.55, p less than 0.02 lying). Such a correlation was not present in the healthy subjects. A reduction in POBF occurred in both groups on assuming the supine posture (healthy subjects 83 (16) SEM microliters/min, LTG subjects 52 (17) SEM microliters/min). These figures represent reductions of 19% and 17% respectively in comparison with the standing value. The results lend further confirmation to the hypothesis that vascular factors are associated with low tension glaucoma.

Adult↗

Eyedrop instillation for reluctant children.

Pupillary responses to pilocarpine eyedrops applied by different techniques have been studied in healthy volunteer subjects. In particular a novel method was evaluated in which eyedrops were applied to the inner canthus with eyes tightly closed and the subject supine, followed immediately by opening of the eyes. The response to this technique indicates that drug penetration into the eye was 66% (confidence intervals 28 to 104%) of that obtained by conventional instillation, into the conjunctival sac, with or without 2 min pressure on the inner canthus. This method of instillation, which is free of aggravation, may be clinically useful for patients, especially children, unwilling or unable to tolerate conventional instillation.

Adult↗

Phagocytosis of protein coated colloidal-gold-agarose-gelatin microbeads by cultured uterine glandular epithelial and stromal cells.

A procedure for fixing and immunostaining whole cells from primary cultures of ovine and bovine uterine gland fragments was used to identify keratin in intermediate filaments of epithelial cells to distinguish them from stromal cells. Colloidal gold encapsulated agarose-gelatin microbeads were coated with different proteins and used to investigate uptake by epithelial and stromal cells in culture. Microbeads were taken up by stromal cells and by epithelial cells on the outskirts of colonies. These cells formed ridges where they contacted and grew above stromal cells. Electron microscopy demonstrated that the microbeads had been internalized and appeared to be nontoxic. Individual cells could harbor more than 90 microbeads within their cytoplasm for at least seven to ten days with no apparent harm. Some cells with microbeads were seen to divide.

Animals↗

Isolation of large numbers of chromosome 3-specific cosmids containing clusters of rare restriction-endonuclease sites.

We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restriction endonucleases to liberate small fragments which were tested as unique-sequence chromosome 3-specific hybridization probes and for evolutionary sequence conservation. Unique-sequence hybridization probes isolated from the cosmids were hybridized to a somatic cell hybrid deletion mapping panel to subchromosomally localize the cosmids. Fragments from many of these cosmids demonstrated conservation of sequence through evolution, and these fragments hybridize to distinct transcripts. These cosmids should therefore prove a useful resource for the identification of many chromosome 3-specific genes, in addition to having potential use as linking clones for pulsed-field gel mapping studies.

Biological Evolution↗

A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies.

1. The cardiovascular effects of the proprietary cold remedies, Mu-cron and Boots Cold Relief tablets were compared with 'placebo' Boots Pain Relief tablets in a double-blind study involving 16 healthy volunteers. Measurements (impedance cardiography, forearm plethysmography) were made over 4 h after oral drug administration. 2. Two Mu-cron tablets (containing phenylpropanolamine [(1R,2S)- plus (1S,2R)-norephedrine] 50 mg) increased blood pressure (maximal effect 18 +/- 1/8 +/- 1 mm Hg (mean +/- s.e. mean), P less than 0.001), stroke volume (4.9 +/- 0.8 ml m-2, P less than 0.05), total peripheral resistance (243 +/- 27 dyn s cm-5 m2, P less than 0.001) and forearm vascular resistance (1.3 +/- 0.3 mm Hg ml-1 min, P less than 0.01) and reduced the ratio of pre-ejection period to ventricular ejection time (-0.031 +/- 0.003, P less than 0.05) and forearm blood flow (-2.6 +/- 0.5 ml min-1, P less than 0.05) but did not affect heart rate or cardiac index. 3. Two Boots Cold Relief tablets (containing phenylephrine 10 mg and caffeine 60 mg) caused a small and short-lived increase in total peripheral resistance but did not have consistent effects on other measurements. Two Boots Pain Relief tablets (containing caffeine 60 mg) did not have important cardiovascular effects. 4. The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1-adrenoceptor agonist action. While it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

A donation to life: organ procurement.

1. Only 15% of brain dead patients become organ donors. This is due to a lack of public education regarding the benefits of organ donation, lack of recognition of potential donors, poor donor management, and unfortunately, even the reluctance of health-care workers to approach families with the choice to donate. 2. Once the patient has been officially accepted as an organ donor and the consents have been signed, the donor goes through a thorough evaluation involving physician consultations and lab work, and the medical history is reviewed for possible complications. 3. As many as four surgical teams may be involved in organ procurement, and good communication between nurses, physicians, and coordinators is vital to promote successful recovery of donor organs.

Brain Death↗

Uncemented total hip arthroplasty. Prospective analysis of the tri-lock femoral component.

Fifty consecutive hip disease patients (56 hips) with total hip arthroplasties (THA) utilized the uncemented Tri-Lock femoral component. Forty-five patients (51 hips) were followed for an average of 46 months (range, 24-66). Forty-two patients (47 hips) were followed with clinical examination and roentgenographs, three (four hips) by telephone interview, four (four hips) were deceased, and one (one hip) was lost to follow-up evaluation. The diagnoses included osteoarthritis (30 hips), avascular necrosis (11 hips), juvenile rheumatoid arthritis (two hips), and degenerative joint disease secondary to childhood hip disorder (four hips). Of 47 hips, 34 were graded excellent, seven good, three fair, and three poor using the Harris hip score. The incidence of thigh pain was 19% at one year, but only 6% at final follow-up evaluation. Limp persisted in 19% of the patients. Of the three patients with four hips contacted by telephone, two had slight pain and two had no pain. The roentgenographic results found an alarming 38% incidence of varus shift of the components, relative to their preoperative position. The presence of a varus shift did not adversely affect the clinical results. Early experience with the Tri-Lock femoral component shows results comparable to those reported in the literature. The high incidence of femoral component shift, presumably because of geometry of the stem is of concern. Longer follow-up evaluation will be necessary to determine the fate of these uncemented THA operations.

Adolescent↗

Absenteeism control programs. Results of a national survey of certified occupational health nurses.

An absenteeism control program can reduce employee absenteeism, thereby reducing company expenses, improving productivity, and bringing workers back to work sooner. A survey of Cohn's suggests that many companies in the United States lack absenteeism control programs, and those firms that have such programs are unlikely to have all the elements of a good program in place. Placing the occupational health nurse in charge of a comprehensive program will provide needed leadership, responsibility, expertise, and control.

Absenteeism↗

Inositolhexakisphosphate is convulsant in mice and rats in the nanomolar range.

The effect of i.c.v. administration of dodecasodium and dicalcium inositolhexakisphosphate (Na12IP6 and Ca2IP6, respectively) to mice and rats was studied. In mice, Na12IP6 (1-300 nmol) or Ca2IP6 (10-500 nmol) induced: ataxia, ground-hugging, tremor (often continuous), scratching, hyperlocomotion, wild running, myoclonic jerks, jumping, clonic muscle spasms, tonic seizure, followed by death or full recovery. The CD50 values for clonic seizures for Na12IP6 and Ca2IP6 were 16 and 49 nmol, respectively. The convulsant effect of Na12IP6 (15 nmol i.c.v.) was not blocked by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate, but was dose dependently reduced by pretreatment with CaCl2 (30-60 nmol i.c.v.) and abolished by coadministration of CaCl2 (30 nmol) with Na12IP6 (i.c.v.). In rats, Na12IP6 (50 nmol i.c.v.) induced severe electroencephalographic seizures in the hippocampus and cortex. The potent convulsant effect of IP6 (administered i.c.v.) depends at least in part on a calcium-chelating action.

Animals↗

Receptor site specificity for the acute effects of beta-N-methylamino-alanine in mice.

DL-beta-N-methylamino-alanine (DL-BMAA; 1-10 mumol i.c.v.) in mice induced a syndrome of: ataxia, ptosis, scratching, jumping, myoclonic jerks, clonic muscle spasms and tonic seizure, which was unaffected by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate (D(-)-CPPene; i.p.), or by co-administration of gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS with DL-BMAA; i.c.v.). Pretreatment with 1-(aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; i.v.) decreased the incidence of clonic seizures for DL-BMAA, kainic acid and RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (RS-AMPA; i.c.v.). These results suggest an involvement of the AMPA/quisqualate subtype of excitatory amino acid receptors in acute BMAA toxicity.

Amino Acids, Diamino↗

A specific inhibitor of the ubiquitin activating enzyme: synthesis and characterization of adenosyl-phospho-ubiquitinol, a nonhydrolyzable ubiquitin adenylate analogue.

A nonhydrolyzable analogue of ubiquitin adenylate has been synthesized for use as a specific inhibitor of the ubiquitination of proteins. Ubiquitin adenylate is a tightly bound intermediate formed by the ubiquitin activating enzyme. The inhibitor adenosyl-phospho-ubiquitinol (APU) is the phosphodiester of adenosine and the C-terminal alcohol derived from ubiquitin. APU is isosteric with the normal reaction intermediate, the mixed anhydride of ubiquitin and AMP, but results from the replacement of the carbonyl oxygen of Gly76 with a methylene group. This stable analogue would be expected to bind to both ubiquitin and adenosine subsites and result in a tightly bound competitive inhibitor of ubiquitin activation. APU inhibits the ATP-PPi exchange reaction catalyzed by the purified ubiquitin activating enzyme in a manner competitive with ATP (Ki = 50 nM) and noncompetitive with ubiquitin (Ki = 35 nM). AMP has no effect on the inhibition, confirming that the inhibitor binds to the free form of the enzyme and not the thiol ester form. This inhibition constant is 10-fold lower than the dissociation constants for each substrate and 30-1000-fold lower than the respective Km values for ubiquitin and ATP. APU also effectively inhibits conjugation of ubiquitin to endogenous proteins catalyzed by reticulocyte fraction II with an apparent Ki of 0.75 microM. This weaker inhibition is consistent with the fact that activation of ubiquitin is not rate limiting in the conjugation reactions catalyzed by fraction II. APU is similarly effective as an inhibitor of the ubiquitin-dependent proteolysis of beta-lactoglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗

The cardiovascular effects of oral nifedipine and nicardipine: a double-blind comparison in healthy volunteers using transthoracic bioimpedance cardiography.

The cardiovascular effects of single oral doses of nifedipine (5 and 10 mg) and nicardipine (20 and 30 mg) were compared in a placebo controlled double-blind crossover study involving 8 healthy male volunteers. Two hours following drug administration stroke volume and cardiac index were measured non-invasively using transthoracic electrical bioimpedance cardiography during passive tilting, graded bicycle exercise, and recovery from exercise. Two separate experiments were performed in the absence of active drug to allow the reproducibility of the measurements to be assessed. Coefficients of variation (within experiment/between experiments) for cardiac index were 7.0%/19.9% at rest and 11.5%/9.3% at 180 W exercise. Both nifedipine and nicardipine increased stroke volume and cardiac index and reduced total peripheral resistance (mean blood pressure/cardiac index) at all times in the experiment. Reductions in peripheral resistance were similar for nifedipine 10 mg and nicardipine 20 mg but in these doses slightly larger increases in heart rate were produced by nifedipine, and in stroke volume and cardiac index with nicardipine. The study shows that the cardiovascular effects of nifedipine and nicardipine can be detected using impedance cardiography which is a simple, safe, and inexpensive technique. The differences between the effects of the two drugs were small. Although some were of statistical significance and are consistent with a less marked cardiodepressant effect for nicardipine, the clinical importance of these observations is uncertain. Further studies to examine the effect of oral nifedipine and nicardipine in patients with impaired ventricular function may be helpful in clarifying this tissue.

Administration, Oral↗