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Biomedical subjects

A Heald

Publications and source records attributed to A Heald.

30 records · Page 2Linked to original sources
PubMed1993

Adult bacterial nasopharyngitis: a clinical entity?

OBJECTIVE: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. DESIGN: Prospective case series. SETTING: Walk-in medical clinic of a university hospital. PATIENTS: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. MEASUREMENTS AND MAIN RESULTS: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 334 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes. Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6-14.2), Moraxella catarrhalis (odds ratio 12.9, 95% confidence interval 3.1-79.5), and Hemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2-7.4) were all associated with the presence of leukocytes. In contrast, nasopharyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were "pathogenic" bacteria found. CONCLUSIONS: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

Adolescent↗
PubMed1993

Longitudinal study of central motor conduction time following stroke. 1. Natural history of central motor conduction.

A 12 month longitudinal study has been performed on 118 subjects following first-ever stroke to determine changes in central motor conduction time (CMCT) to upper limb muscles. The responses to electromagnetic stimulation of the motor cortex and cervical motor roots were recorded bilaterally in the surface electromyograms of pectoralis major, biceps and triceps brachii and thenar muscles. The CMCTs obtained from these recordings in stroke patients have been compared with those obtained in 53 normal healthy subjects of a similar age. The first measurements were made within the immediate post-stroke period (12-72 h of the onset of symptoms) and repeated at set time intervals over 12 months. The first assessment of CMCT identified three groups: those with normal responses, delayed responses and absent responses. During the first 12 months following stroke various changes in CMCT occurred. Central motor conduction time may remain unchanged, delayed CMCT may return to normal and previously absent responses may reappear and be delayed or normal. Using electromagnetic stimulation of the motor cortex the thresholds for motor evoked responses in the different muscles were initially high and fell over 12 months.

Adult↗
PubMed1993

Longitudinal study of central motor conduction time following stroke. 2. Central motor conduction measured within 72 h after stroke as a predictor of functional outcome at 12 months.

A longitudinal study was performed on 118 first-ever stroke patients to evaluate neurophysiological measurements of central motor conduction time (CMCT) in the period immediately following stroke as predictors of functional outcome and mortality at 12 months. Measurements of CMCT were made as described in the accompanying article (Heald et al., 1993, Brain, 116, 1355-1370), in which the following three groups of patients were recognized within 12-72 h after the onset of symptoms: normal response group, delayed response group and no response group. Neurophysiological and clinical investigations were commenced 12-72 h (designated as day 1) after the onset of symptoms and repeated at set time intervals up to 12 months. The subjects were examined neurologically and assessed using the Motricity Index for muscle strength, the Nine-hole Peg Test to measure manual dexterity, the Barthel Score for activities of daily living and the modified Rankin Scale for functional outcome. The duration of stay in hospital and the occurrence of stroke-related death were noted. During the first week following stroke, absence of responses correlated closely with the patient's symptoms and neurological observations of abnormal muscle tone and tendon reflexes. Correlations were made in the three groups of patients of functional scores at day 1 and at 12 months. Patients with normal CMCT had consistently higher scores throughout the 12 month period and achieved significantly better functional recovery. Patients with no responses showed poor performance in neurological and functional tests throughout the 12 month period. Patients with delayed CMCT had neurological and functional scores intermediate between those of the other two groups, but outcome at 12 months was similar to those in the normal response group. Where the threshold to cortical stimulation was abnormally high, functional outcome was generally poor. Mortality was highest in the group with absent responses and the survivors spent the longest period in hospital. In conclusion, the observation of normal or delayed CMCT at day 1 identifies a group of patients with a high probability of survival and functional recovery. The absence of responses to cortical stimulation at day 1 identifies a group of patients who are at high risk of poor functional recovery at 12 months and greater probability of stroke-related death during this period.

Cerebrovascular Disorders↗
PubMed1993

L-694,247: a potent 5-HT1D receptor agonist.

1. The 5-hydroxytryptamine (5-HT) receptor binding selectivity profile of a novel, potent 5-HT1D receptor agonist, L-694,247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]- 1H-indole-3-yl]ethylamine) was assessed and compared with that of the 5-HT1-like receptor agonist, sumatriptan. 2. L-694,247 had an affinity (pIC50) of 10.03 at the 5-HT1D binding site and 9.08 at the 5-HT1B binding site (sumatriptan: pIC50 values 8.22 and 5.94 respectively). L-694,247 retained good selectivity with respect to the 5-HT1A binding site (pIC50 = 8.64), the 5-HT1C binding site (6.42), the 5-HT2 binding site (6.50) and the 5-HT1E binding site (5.66). The pIC50 values for sumatriptan at these radioligand binding sites were 6.14, 5.0, < 5.0 and 5.64 respectively. Both L-694,247 and sumatriptan were essentially inactive at the 5-HT3 recognition site. 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5-HT1D receptor mediated functional response. L-694,247 (pEC50 = 9.4) was also more potent than sumatriptan (6.5) in a second 5-HT1D receptor mediated functional response, the inhibition of K(+)-evoked [3H]-5-HT release from guinea-pig frontal cortex slices. 4. The excellent agreement observed for L-694,247 between the 5-HTlD radioligand binding affinity and the functional potency confirm that the two functional models (the inhibition of forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra and the inhibition of K+-evoked [3H]-5-HT release from guinea-pig frontal cortex) do indeed reflect 5-HTID-mediated events.5. L-694,247 is a novel, highly potent 5-HTID/5-HTIB receptor ligand which should prove useful for the exploration of the physiological role of these receptors in animals.

Adenylyl Cyclases↗
PubMed1992

Reversal of cognitive impairment by heptyl physostigmine, a long-lasting cholinesterase inhibitor, in primates.

Cholinergic replacement therapy for Alzheimer's disease using existing cholinesterase inhibitors is compromised by short duration, meagre benefits restricted to subgroups of patients, and peripheral toxicity. Heptyl physostigmine is a lipophilic carbamate derivative of physostigmine. In rhesus monkeys, heptyl physostigmine (0.2-0.9 mg/kg i.m.) fully reversed a scopolamine-induced cognitive impairment. Following oral administration in squirrel monkeys, heptyl physostigmine (8 mg/kg) induced long-lasting hypothermia (greater than or equal to 4 h), a centrally-mediated cholinergic effect. Erythrocyte acetylcholinesterase activity was inhibited by 86% at the time of peak hypothermia (180 min). Clinical trials with heptyl physostigmine will enable a more rigorous evaluation of cholinomimetic therapy for dementia.

Acetylcholinesterase↗
PubMed1991

Treatment for cerebral toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with AIDS. The Swiss HIV Cohort Study.

OBJECTIVE: To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Cohort study. SETTING: Switzerland. PATIENTS: A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS: Life-table analysis for P. carinii-free survival. MAIN RESULTS: Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION: Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides.

Acquired Immunodeficiency Syndrome↗
PubMed1988

A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease.

Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.

Alzheimer Disease↗
PubMed1988

Planning and spatial working memory in Parkinson's disease.

The higher level cognitive function of planning was studied in a group of medicated Parkinson's disease patients and a group of matched control subjects, using a computerised version of Shallice's Tower of London task. Baseline measurement of the ability to execute a given plan of action, to generate low level strategies required for efficient searching, and spatial working memory capacity, all of which contribute to performance on the planning task, established that the Parkinson's disease group was unimpaired on any of these measures. On the Tower of London task, the Parkinson's disease group was also unimpaired in terms of the average number of moves required to solve a problem. However, a specific planning deficit was evident when "thinking" times were analysed, and this was after the confounding influence of motor initiation and execution times had been carefully extracted from total performance times. This finding is discussed in relation to putative functions of the frontal lobes and basal ganglia, and an attention-switching hypothesis is developed to account for it.

Aged↗
PubMed1984

Elimination kinetics of captopril in patients with renal failure.

Captopril kinetics were determined after a 100-mg oral dose of 14C-captopril in 21 patients with various degrees of renal impairment. Elimination kinetics of captopril were evaluated by model-independent methods. The body clearance (ClB) of captopril decreased steadily with decreasing creatinine clearance (ClCr) from 5.2 ml/min/kg for mild renal failure patients to 1.6 ml/min/kg for hemodialysis patients during an interdialytic period. In patients with mild renal impairment, renal and nonrenal clearances of captopril averaged 2.2 and 3.0 ml/min/kg, respectively, and fell (P less than 0.001) to 0.2 and 1.5 ml/min/kg in patients with severe renal impairment. There were no significant differences in the extent of total cumulative excretion (fecal plus urinary) of radioactivity over a 96- to 120-hr period between the patients with mild, moderate, and severe renal impairment. The 48-hr renal excretion of captopril averaged 29, 21, and 8% of the dose in the mild, moderate, and severe renally impaired groups. In five additional hemodialysis patients, the mean dialyzer clearance of captopril averaged 120 ml/min. Approximately 35% of the dose was recovered in the 4-hr dialysate. Based on the above findings, a reduction in the dose of captopril is necessary in patients with renal failure.

Adult↗
PubMed1976

Physical characterization and activity in vivo of polymorphic forms of 7-chloro-5, 11-dihydrodibenz[b, e][1, 4]oxazepine-5-carboxamide, a potential tricyclic antidepressant.

The biological availability in dogs and humans of 7-chloro-5, 11-dihydrodibenz[b,e][1,4]oxazepine-5-carboxamide, a potential antidepressant drug, was increased when the compound was administered in capsule formulations as micronized drug coated with 1% sodium lauryl sulfate or as a lyophilate with poloxamer 407. This increase with these two formulations had been predicted by dissolution tests in vitro. The lyophilized combination with poloxamer 407 was more soluble in 0.1 N HCl than was the untreated compound. Characterization of the lyophilate by differential thermal analysis, X-ray diffraction, and IR spectroscopy indicated that the increase in solubility was attributable to the formation of a polymorphic from. a polymorph of the compound designated form 8, was prepared. The solubility and dissolution characteristics of the two polymorphic forms, A and B, as well as of the lyophilized combination with poloxamer 407, were determined.

Adult↗