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Biomedical subjects

R Richards

Publications and source records attributed to R Richards.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effect of nedocromil sodium and sodium cromoglycate against bronchoconstriction induced by inhaled adenosine 5'-monophosphate.

In this randomized, double-blind, placebo controlled study, the effect of prior inhalation of nebulized sodium cromoglycate (SCG) (7.3 +/- 0.6 mg) and nedocromil sodium (NED) (7.5 +/- 0.6 mg) was observed on adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in 11 non-atopic asthmatic subjects. The geometric mean provocation doses of methacholine and AMP required to produce a 20% decrease in forced expiratory volume in one second (FEV1) (PD20FEV1) were 0.6 (0.1-18.8) and 5.1 (0.8-130.7) mumole respectively. The repeatability of the AMP challenge procedure for PD20FEV1 was within one doubling dose difference. SCG and NED, administered 30 min prior to bronchoprovocation with AMP, displaced the AMP dose-response curve to the right by 9.6 (1.5-41.6) (p less than 0.01) and 22.2 (3.7-89.1) (p less than 0.01)-fold, respectively, the difference between the two drugs being significant (p less than 0.05). There was a significant correlation (r = 0.7, p = 0.02) between the log dose ratios for PD20FEV1 for SCG and NED. We conclude that both SCG and NED protect against AMP-induced bronchoconstriction, NED being at least 2.3 (0.7-11.5)-fold more potent than SCG, and that they achieve this effect by a similar mechanism(s).

Adenosine Monophosphate↗
PubMed1988

Essential iris atrophy. A clinical, immunohistologic, and electron microscopic study in an enucleated eye.

A 29-year-old woman had unilateral essential iris atrophy, corneal endothelial changes, and absolute glaucoma. The enucleated eye was examined by routine light microscopy. Separate portions of unfixed fresh frozen cornea were sectioned and reacted with monoclonal antibodies against keratins, vimentin, and inflammatory cell markers. Stains for filamentous actin (f-actin) were performed using the 7-nitro-benz-2-oxa-1,3-diazolylphallacidin (NBD phallacidin) probe. In addition, portions of cornea and iris were examined by scanning and transmission electron microscopy. Immunocytochemical stains with anti-keratin antibodies showed reactivity only in the corneal epithelium of the patient and normal control. Immunoreactivity with anti-vimentin antibodies was observed in corneal endothelium and keratocytes of the patient and control, but was negative in the epithelium. Staining for f-actin appeared more pronounced in the corneal endothelium of the patient. Scanning electron microscopy of the corneal endothelium showed irregularity in cell size and shape and filopodial processes characteristic of migrating cells. Transmission electron microscopy disclosed abnormalities of Descemet's membrane and endothelium with a posterior collagenous layer. The corneal endothelium displayed normal junctional complexes without desmosomal junctions or increased microvillus projections. Increased 10-nm cytoplasmic filaments were noted consistent with the expression of vimentin. Occasional chronic inflammatory cells perturbed the corneal endothelium and were detected within the endothelial layer. Alterations in the endothelium and Descemet's membrane suggest the acquired nature of this disease.

Actins↗
PubMed1988

Effect of methacholine induced bronchoconstriction on the pulmonary distribution and plasma pharmacokinetics of inhaled sodium cromoglycate in subjects with normal and hyperreactive airways.

Inhalation treatment may be less effective in the presence of bronchoconstriction because of the reduced penetration of drugs into the airways. The effect of bronchoconstriction on the lung deposition and plasma pharmacokinetics of inhaled sodium cromoglycate was examined. Ten subjects attended the laboratory on three occasions. On the first occasion a bronchial provocation test was performed to determine the concentration of methacholine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20). On the two subsequent occasions subjects inhaled either saline or their PC20 methacholine, followed five minutes later by an aerosol containing sodium cromoglycate and stannous phytate labelled with technetium-99m. Twenty minutes later a gamma emission lung scan was performed to determine the intrathoracic deposition of the nebulised aerosol. The central:peripheral (C:P) ratio of lung deposition was then calculated. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for four hours. Methacholine led to a 23.4% (SEM 0.6%) lower FEV1 and a 2.8 times higher C:P ratio than those observed after saline. There was a direct correlation between log PC20 methacholine and the increase in the C:P ratio (r = 0.81). Despite these changes with methacholine, the plasma pharmacokinetics of inhaled sodium cromoglycate were not significantly different after methacholine and after saline, except that the maximum concentration achieved (Cmax) was increased. These observations suggest that the area of cromoglycate deposition and the anatomical site are less important in determining the plasma pharmacokinetics of cromoglycate than is the total dose delivered to the lung.

Administration, Inhalation↗
PubMed1988

A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity.

Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo-controlled trial of 30 mg D-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking D-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted.

Adult↗
PubMed1988

Decidual prolactin (PRL)-releasing factor stimulates the synthesis of PRL from human decidual cells.

Previous studies from our laboratory demonstrated that the acute release of PRL from human decidual tissue is stimulated by a 23.5 kilodalton placental protein which we designated decidual PRL-releasing factor (PRL-RF). To determine whether PRL-RF may also affect the synthesis of PRL and/or cause a secondary increase in PRL release, we have examined the effects of purified PRL-RF on the synthesis and release of PRL over a 96-h period. Exposure of dispersed decidual cells to PRL-RF (0.5 microgram/ml) stimulated a biphasic increase in PRL release with acute transient stimulation during the first 0.5 h and a delayed and sustained stimulation beginning about 8 h after exposure which persisted for the duration of the 96 h. The amounts of PRL released from PRL-RF-exposed cells after 0.5, 8, 12, 24, and 96 h were 321.2 +/- 36.2 (mean +/- SEM, n = 3), 110.2 +/- 5.3, 138.2 +/- 7.2, 194.5 +/- 11.2, and 201.5 +/- 14.2% that of control cells. Studies of the de novo synthesis of [35S]methionyl PRL indicated that the increase in PRL release after the first few hours of exposure to PRL-RF was secondary to an increase in PRL synthesis. Somatostatin (100 nM) inhibited the acute stimulatory effect of PRL-RF, but had no effect on the delayed stimulation of PRL release. On the other hand, cycloheximide (20 microM) completely inhibited the secondary increase in PRL release in response to PRL-RF but had no effect on the acute release. These results demonstrate that PRL-RF stimulates both the synthesis and release of decidual PRL.

Cells, Cultured↗
PubMed1988

Somatosensory evoked potential monitoring accurately predicts hemi-spinal cord damage: a case report.

Separate somatosensory evoked potentials (SEPs) were monitored from each lower extremity during instrumentation for a spinal fracture. The SEP disappeared from the right lower extremity after instrumentation, but not from the left lower extremity. The predicted hemi-spinal cord injury was pathologically confirmed. The merits of sequential, as opposed to simultaneous, stimulation of multiple extremities during surgical monitoring are discussed.

Aged↗
PubMed1988

Factors that may effect the reduction of hunger and body weight following d-fenfluramine administration.

Three studies have been undertaken to investigate why there are individual differences in the response to d-fenfluramine with respect to food intake and hunger in the short term and on body weight loss in the long term. Fenfluramine and norfenfluramine plasma levels have been used as probes to help detect and normalize these variances. In a single dose ranging volunteer study (0, 30, 40, and 60 mg), d-fenfluramine levels were significantly related to caloric intake and hunger rating scales when compared individually, and the slopes of the regression lines showed intersubject variation. These slopes, an index of each subject's response to fenfluramine, appear to be related to both the percentage underweight and more weakly to the percentage overweight. Those subjects at the extremes of weight showed a greater response to a given drug level. In two placebo-controlled 3 month studies (30 mg/day), the variances in weight loss were not explained by steady state drug levels, the percentage overweight, initial weight, duration of obesity, or caloric intake even when weight loss was normalized for differences in drug levels. Age, however, was significantly related to weight loss, with each additional 10 years increasing weight loss by approximately 1 kg. If confirmed, the sensitivity of fenfluramine anorexia may be an objective acute test of the central control of food intake. However, in long term clinical studies, drug levels were only weakly related to weight loss and other undefined factors seem to determine which patients responded better to fenfluramine treatment.

Adult↗
PubMed1988

Inhalation rate of sodium cromoglycate determines plasma pharmacokinetics and protection against AMP-induced bronchoconstriction in asthma.

We have investigated whether the inspiratory flow at which sodium cromoglycate (SCG) is inhaled influences the efficacy of SCG. Seven atopic asthmatic subjects (age 25 +/- 2 yrs) inhaled dry powder SCG from a Spinhaler on separate occasions at three flow rates, maximum (V1), 100 l.min-1 (V2), and 50 l.min-1 (V3), or placebo, according to a double-blind structured study. Thirty minutes after administration a bronchial provocation test was performed with adenosine 5'-monophosphate (AMP). Blood samples for measurement of plasma SCG concentration were taken and the area under the plasma concentration-time curve (AUC) calculated for each flow rate. Both inspiratory flow rate and AUC correlated significantly with the degree of protection afforded against AMP-induced bronchoconstriction (r = 0.73, p less than 0.001; r = 0.66, p less than 0.001). These findings indicate that the flow rate used to inhale powdered SCG is a major factor in determining the protective efficacy of this drug against bronchial challenge and therefore has important clinical implications.

Adenosine Monophosphate↗
PubMed1988

Supracondylar fractures of the humerus--results of surgical treatment.

Forty-eight patients with supracondylar fractures of the humerus have been treated at St. Michael's Hospital in the past 10 years. Forty-six of the 48 were treated surgically. A comparison was made between the use of standard AO (ASIF) plates with a pre-contoured plate especially designed for the distal humerus. The results of this comparison suggested that the specifically designed plate provided superior fixation and better anatomic restoration of the distal humerus. Anatomic reduction, rigid fixation, and early surgery provide the best results.

Adult↗
PubMed1987

Purification of decidual prolactin-releasing factor, a placental protein that stimulates prolactin release from human decidual tissue.

Decidual prolactin-releasing factor (PRL-RF), a placental protein that stimulates the release of prolactin from human decidual tissue, has been purified from conditioned medium of human placental explants. The purification scheme consisted of ethanol extraction, anion exchange chromatography on DEAE-cellulose, size exclusion chromatography on Spherogel TSK-3000, and either a) immunoaffinity chromatography using an antiserum to a partially purified PRL-RF preparation or b) acetic acid-urea/SDS 2-dimensional PAGE. The apparent molecular weight of the purified releasing factor, estimated by SDS-PAGE, was 23,500 Da; and the half-maximal dose for the acute stimulation of prolactin release from human decidual cells was 0.05-0.1 ug/ml (2.2-4.4 nM).

Biological Assay↗
PubMed1987

Heat shrinkage of extraocular muscle tendon.

We have designed and employed a bipolar heating device to shorten extraocular muscles. Treatment involves placing the unidirectional heating device on the sclera with the active surface beneath the tendinous portion of the extraocular-muscle. When power is applied, visible tissue shrinkage occurs. Heat-induced extraocular muscle shrinkage was performed on live rhesus monkeys. Two months later, thermal tendinoplasty-treated extraocular muscles were surgically isolated and evaluated for strength. Biopsies were then performed on these muscles. It was our clinical impression that treated tissues retained their strength, while histologic and electron-microscopic evaluation of heat-treated tendon revealed evidence of shrinkage and compaction of collagen bundles. Thermal tendinoplasty may offer a sutureless method of correcting strabismus by shortening and thereby strengthening extraocular muscles.

Animals↗
PubMed1987

Isotype and cytotoxicity spectra of anti-lymphocyte antibodies in patients with systemic lupus erythematosus.

IgG anti-lymphocyte antibodies (ALA) reactive with resting lymphocytes were demonstrated in sera of patients with systemic lupus erythematosus (SLE) by immunofluorescence and flow cytometry and were shown (i) to bind T cells by non-Fc receptor-related mechanisms, (ii) to potentiate antibody-dependent cellular cytotoxicity (ADCC) of lymphocytes in vitro which correlated with binding to T cells, and (iii) to occur at a similar frequency in 29 SLE sera (56%) as IgM ALA (59%). IgG ALA levels in sera negatively correlated with absolute numbers of circulating lymphocytes in patients (r = -0.48, P less than 0.05), as did IgM ALA levels (r = -0.54, P less than 0.05); however, a stronger correlation resulted when levels of both ALA isotypes were considered together (r = -0.61, P less than 0.01). Different groups of SLE patients were distinguished with respect to relative serum content of IgM and IgG ALA and corresponding serum capacity to predominantly mediate ADCC, complement-dependent cytotoxicity (CDC), or both. No correlation existed between serum ADCC and CDC activities in vitro (r = 0.22). However, SLE patient lymphocyte counts negatively correlated with ADCC (r = -0.59, P less than 0.01) and to a lesser but still significant extent with CDC (r = -0.47, P less than 0.05). The latter results suggested that ADCC, induced by serum IgG ALA, was a mechanism of cytoloysis which occurred independently of CDC and which, like CDC, was significantly associated with lymphopenia in vivo.

Autoantibodies↗
PubMed1987

A social casework contribution to understanding alcoholism.

This article describes a 40-year longitudinal study of alcoholism including the etiology of, progression of, and recovery from the disease. The findings are paralleled with similar studies conducted by social work professionals. The capacity of a longitudinal study to elucidate alcoholism and the recovery process is underscored. The etiological hypothesis that views alcoholism primarily as a symptom of psychological instability is questioned.

Alcoholism↗
PubMed1987

Comparison of the airway response to eye drops of timolol and its isomer L-714,465 in asthmatic subjects.

1. The inadvertent administration of timolol to asthmatic patients continues to cause occasional severe and even fatal attacks of asthma. The (R)-enantiomer of timolol, L-714,465, is four times less potent than timolol in reducing intraocular pressure in man. It is 49 times less potent than timolol on beta 2-adrenoceptors in animals and 13 times less potent on the airways of normal subjects. These findings suggested that L-714,465 might be a safer alternative for the treatment of glaucoma. 2. Ten subjects with mild asthma who bronchoconstricted to timolol eye drops (0.25 or 0.5%) were studied. Airway dose-response curves to timolol (0-2%), L-714,465 (0-4%), and placebo (methyl cellulose) eye drops were performed in a double-blind randomised study in which airway response was measured as change in FEV1 and specific airway conductance (sGaw). 3. L-714,465 and timolol caused dose dependent falls in sGaw and FEV1 with L-714,465 being approximately four times less potent than timolol. The geometric mean dose ratio was 3.89 for FEV1 (95% confidence interval (CI) 1.7-8.7) and 3.93 (95% CI 2-7.8) for sGaw. Since the difference in potency is similar to the reported difference in potency of the two drugs on intraocular pressure we conclude that L-714,465 would not have a greater safety margin than timolol. 4. After completion of the dose-response study eight subjects inhaled ipratropium bromide (72 micrograms) and this caused an increase in FEV1 from 74% to 80% of baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Effects of aortic occlusion on regional spinal cord blood flow and somatosensory evoked potentials in sheep.

Somatosensory evoked potentials (SEPs) were recorded continuously during aortic occlusion in sheep, with simultaneous measurement of spinal cord blood flow (SCBF) by radiolabeled microspheres. Aortic occlusion was associated with disappearance of the SEPs in seven of nine sheep in 7.8 +/- 4.1 (SD) minutes. SCBF at the time of initial cross clamping and 30 minutes after the onset of ischemia revealed a severe reduction in white and gray matter flow in the thoracolumbar cord. Release of the aortic clamp was associated with reactive hyperemia in these ischemic regions. In two animals, the SEP persisted during aortic cross clamping. The total SCBF in the thoracic and lumbar regions of these two animals exceeded 20 ml/100 g/min after 30 minutes of ischemia and was significantly greater than the flow recorded in sheep whose evoked response disappeared. The relation between spinal cord ischemia and evoked potential alterations is discussed in detail.

Afferent Pathways↗
PubMed1987

Absorption and disposition kinetics of cromolyn sodium and the influence of inhalation technique.

Plasma concentrations of cromolyn sodium (SCG) have been measured in 13 normal subjects on three occasions after inhalation from a Spinhaler (20 mg) delivery system under conditions of controlled inspiratory flow rate. High inspiratory flow rates were associated with high peak plasma concentrations and areas under the plasma concentration-time curve. A 10-sec breath hold at the end of inspiration did not alter significantly the plasma concentration-time curve. Instillation of SCG (1 mg) directly into a second-order bronchus of 14 patients undergoing diagnostic examination gave plasma concentration-time curves similar to those seen in normal volunteers at high inspiratory flow rates. Additional studies in normal volunteers showed that SCG was poorly absorbed from the gastrointestinal tract. The shorter terminal half-life seen after i.v. infusion compared with inhalation indicates that the drug shows absorption rate limited disposition kinetics after inhalation. These studies in large numbers of subjects support the conclusions of limited earlier investigations that SCG is absorbed slowly but almost completely from the airways, that there is little gastrointestinal absorption of SCG, that only a small proportion of the Spinhaler dose (about 10%) reaches the airways and that the amount reaching the airways is related directly to inspiratory flow rate.

Administration, Inhalation↗