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Biomedical subjects

P Holst

Publications and source records attributed to P Holst.

14 recordsLinked to original sources

Comparison of nedocromil sodium at two dosage frequencies with placebo in the management of chronic asthma.

Nedocromil sodium (4 mg b.d. or q.i.d.) was added to the therapy of 76 chronic asthmatic patients in a four-centre, double-blind cross-over, placebo-controlled trial. Patients had troublesome symptoms uncontrolled by high doses of inhaled corticosteroids (mean 1450 micrograms). In 54 patients who completed the study, nedocromil sodium was significantly more efficacious than placebo (P < 0.01) in relieving morning chest-tightness and cough, in reducing total diary card score and nocturnal bronchodilator usage, and in increasing morning and evening peak flow. Asthma severity at clinic visits decreased significantly (P = 0.001) following treatment with nedocromil sodium, which was globally rated more effective than placebo (P < 0.01). Treatment differences favored q.i.d. over b.d. dosage but without statistical significance. There were no serious adverse effects. Although the pulmonary function changes were small, these findings suggest that the addition of nedocromil sodium may benefit asthmatic patients who are inadequately controlled by high doses of inhaled corticosteroids.

Adolescent

Cognitive test performances related to early and late computed tomography findings after closed-head injury.

Computed tomography (CT) findings from early (less than 24 hours) and late scan (6 months) after closed-head injury (CHI) were compared to cognitive test scores obtained on an average of 4 months after injury in a consecutive series of 53 patients. The presence of parenchymal lesion was associated with poor test results, indicating cognitive inflexibility and disinhibition of routine response tendencies in novel tasks. These deficits have previously been found to be related in particular to frontal-lobe dysfunction, but the present study did not support the hypothesis that frontal lesion is the principal cause of this impairment in CHI. Parenchymal lesions in the right and left hemisphere were associated with spatial and verbal deficits, respectively. Ventricular enlargement in the late CT was related to cognitive inefficiency, both being strongly associated with age. The results suggest that parenchymal lesion in the early CT is an indicator of diffuse axonal injury, which results in cognitive inflexibility during recovery.

Adolescent

Effects of lidocaine aerosol on postoperative pain and wound tenderness following minor gynaecological laparotomy.

Twenty-four female patients undergoing sterilization through a minor lower laparotomy received, in a double-blind, randomized study, either lidocaine spray 200 mg or placebo in the surgical wound. Postoperative pain intensity was evaluated on a verbal and a visual analogue scale and wound tenderness with an algometer. During mobilisation from the supine to the sitting position, VAS-score was lower (P less than 0.05) in the lidocaine group 2 h postoperatively, but not 4, 6 and 8 h postoperatively (P greater than 0.05). No significant differences were found in VAS-scores at rest or during cough, or in verbal scale ratings during rest, cough or mobilisation, and postoperative consumption of morphine was similar in the two groups. Pressure pain thresholds were higher (P less than 0.05) 2 h postoperatively in the lidocaine group, but not 4, 6 and 8 h postoperatively. In conclusion, topically applied lidocaine aerosol in the surgical wound leads to very short and clinically insignificant relief of postoperative pain.

Aerosols

Mental programming after frontal lobe lesions: results on digit symbol performance with self-selected goals.

The aim of this study was to demonstrate that the inability to set adequate sub-goals in a cognitive task is a sensitive indicator of programming deficit after frontal lobe lesion. Sixty-one patients with focal cerebral lesions and 25 control subjects were studied with a modified Digit Symbol task, in which the score depended on the adequacy of the sub-goals set by the subject. This score was compared to that on the standard condition, in which the subject was requested to work as quickly as possible without self-selected goals. The results confirmed the prediction that patients with anterior lesions set less adequate sub-goals than patients with posterior lesions and, unlike the latter patients, have a more pronounced deficit on the performance with self-selected goals than on the standard condition. In particular patients with left frontal lobe lesions underestimated their capabilities in relation to task requirements.

Adult

Social outcome related to cognitive performance and computed tomographic findings after surgery for a ruptured intracranial aneurysm.

A series of 83 patients was examined with a battery of cognitive tests, a clinical interview, and computed tomography 1 year after surgery for a ruptured intracranial aneurysm. Disability on the Glasgow Outcome Scale (33%), failure to return to work (25%), impaired social relations (25%), and subjective or clinical mental impairment (56%) were found to be related to each other and to poor performance on cognitive tests, especially to verbal impairments in patients with left lateral infarctions and to memory deficits and cognitive inflexibility in patients with frontal medial infarctions. Furthermore, cognitive deficits and poor outcome were associated with diffuse brain damage. Depression and anxiety were unrelated to test performances, but were frequently reported by patients with right lateral infarctions.

Adult

Use of a management plan for treating asthma in an emergency department.

A standardised management protocol has been developed for the assessment and treatment of adults with acute asthma attending an emergency department. The management protocol consists of an assessment sheet for recording essential features of the history and examination findings and a flow diagram with guidelines for initial management that were based on spirometric recordings. The protocol was introduced at Wellington Hospital in 1986. The effect of this intervention was assessed by analysing emergency department records during the three months before and one year after the introduction of the protocol. The use of the assessment sheet improved history taking and led to the increased use of serial measures of airflow obstruction and improved documentation of follow up arrangements. The provision of management guidelines influenced the emphasis of management, including an increased use of corticosteroids intravenously and more frequent use of an additional dose of nebulised bronchodilator. In the light of the initial experience the protocol has been modified and its use either in an emergency department or in general practice is recommended.

Acute Disease

Deficient programming in spatial learning after frontal lobe damage.

Patients with anterior or posterior brain damage and control subjects performed a spatial sequence learning task in which the score obtained depended on the subject's ability to set sub-goals appropriate for his learning capacity. The anterior group obtained lower scores and more frequently set inadequate sub-goals than the posterior group. No anterior vs posterior difference was found on a similar learning task in which another sequence was learnt by predetermined sub-goals. The result supported the hypothesis that frontal lobe lesions disturb programming or goal-based search for action structure on spatial learning.

Adult

Speed-accuracy optimization in acquisition of figures after focal cerebral lesion.

Seventy-seven brain damaged patients and 14 control subjects performed a visual memory test in which the subjects had to reproduce geometric figures from memory after studying the design for 10 seconds (standard condition) and after an observation period subjectively necessary and sufficient for accurate reproduction (self-timed condition). The brain damaged patients were less efficient than the control subjects on the self-timed acquisition even when the covariance on the standard condition was taken into account. The prediction that frontal lobe damaged patients are inferior to posterior brain damaged patients on the speed-accuracy optimization of acquisition was true only in the right hemisphere damaged patients on the simple trials, suggesting that right frontal lobe damage disturbs voluntary attention. Visuospatial errors were typical for right hemisphere damaged patients, perservations for left frontal lobe damaged patients.

Adult

Cognitive deficits related to computed tomographic findings after surgery for a ruptured intracranial aneurysm.

A consecutive series of 118 patients operated on for ruptured intracranial arterial aneurysms was studied. Ninety-six of them could be adequately examined with a battery of psychological tests and computed tomographic scans 1 year after a subarachnoid hemorrhage. Seventeen orthopedic control patients with no history of brain damage were also tested. The pattern of cognitive deficits was strongly related to the findings on the computed tomographic scans. Patients with left lateral infarctions had deficits on performances requiring verbal efficiency, including memory and classification tasks, whereas patients who had right lateral infarctions were poor on a visuoconstructional task (the copying of Rey's Figure). These deficits were pronounced when lateral infarction was associated with diffuse brain damage. Patients with frontal medial infarctions had low scores on memory tests; the inefficiency in verbal fluency, categorical reasoning, and memory was related to diffuse brain damage. The patients who had no infarctions did not differ significantly from the control group. Cognitive impairments after left lateral and frontal medial infarctions, as well as diffuse brain damage, correlated with the Glasgow Outcome Scale.

Brain

Determination of follicle regulatory protein levels in urine during the normal menstrual cycle using an enzyme-linked immunosorbant assay.

A protein from follicular fluid [referred to as follicle regulatory protein (FRP)] which inhibits aromatase activity in granulosa cells was recently isolated and partially characterized. The purified FRP was used to produce a monoclonal antibody which was used to develop an enzyme-linked immunosorbant assay suitable for quantitation of FRP in urine. Twelve normal premenopausal women underwent daily collection of blood and first morning urine samples, beginning on the 1st day of menses, as well as daily ultrasonographic evaluation of follicular diameter, beginning on the 10th day of the menstrual cycle, until the onset of the next menses. Serum estradiol, progesterone, LH, and FSH levels were determined by RIA. Urinary FRP levels increased in the midfollicular phase, reached their zenith in the midluteal phase [mean, 0.38 +/- 0.03 (+/- SE) immunoreactive units; 1 immunoreactive unit = approximately 1 ng FRP/mL.mg creatinine], and then declined to reach their nadir (not detectable) during the early follicular phase. Immunohistochemical evaluation of ovarian tissue demonstrated that anti-FRP localized to mural granulosa cells in viable follicles, to all follicular epithelial cells in atretic follicles, and to the large cells of the corpus luteum. These findings indicate that immunoreactive FRP levels in urine change during the menstrual cycle and suggest a relationship among FRP, follicular maturation, and corpus luteum formation.

Adult

Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget's disease of bone.

Recent ultrastructural and immunohistochemical evidence supports the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family. Conflicting evidence for the presence of respiratory syncytial virus (RSV), a pneumovirus, or measles, a morbillivirus, has been reported. By the indirect fluorescent antibody assay, four RSV antisera were compared with four measles antisera on serial sections of pagetic bone or replicate coverslips of cells from pagetic bone grown in culture from 30 patients. Results produced positive immunofluorescence for RSV in 28 of 29 patients and positive immunofluorescence for measles in 11 of 22 patients. Of the 20 patients from whom comparable samples could be tested for antigens, 11 were found to harbor both antigens. These studies support the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family more closely related to the pneumoviruses than the morbilliviruses.

Antigens, Viral

Hereditary resistance to 1,25-dihydroxyvitamin D: defective function of receptors for 1,25-dihydroxyvitamin D in cells cultured from bone.

UNLABELLED: The syndrome of rickets, alopecia, hypocalcemia, and high circulating levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D) apparently is caused by resistance of target tissues to 1,25-(OH)2D. To evaluate this, we cultured cells from explants of long bone of one patient with this syndrome and from a control without any preexisting disorder of mineral metabolism. The cultured cells showed morphological features of fibroblasts but contained alkaline phosphatase activity without detectable acid phosphatase activity, indicating an osteoblastic origin for some or all of the cultured cells. Receptors for 1,25-(OH)2D were assessed by three methods: high affinity uptake of hormone in nuclei of dispersed cells, high affinity binding in hypertonic extracts (herein termed cytosol) from cells, and sedimentation velocity of bound [3H]1,25-(OH)2D3 in extracts of cell nuclei. With cells cultured from bone of the normal control, receptors for 1,25-(OH)2D exhibited properties indistinguishable from those found with cultured skin fibroblasts. With cells cultured from bone of the patient with resistance to 1,25-(OH)2D, high affinity uptake of 1,25-(OH)2D into nuclei was unmeasurable, but high affinity binding of hormone with cytosol was normal; these abnormal findings also were indistinguishable from abnormal findings obtained with fibroblasts cultured from skin of that patient. IN CONCLUSION: 1) Cells cultured from explants of human bone showed morphological features of fibroblasts but retained a marker enzyme characteristic of osteoblasts. Significant admixture of osteoblast-like cells with fibroblasts was possible. 2) Cells cultured from bone of a patient with familial resistance to 1,25-(OH)2D exhibit a defect in vitamin D metabolism, indistinguishable from the defect observed with cells cultured from skin of the same patient.

Acid Phosphatase