Undergraduate examinations--a continuing tyranny.
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Clinical Competence↗
Biomedical subjects
R C Godfrey
Publications and source records attributed to R C Godfrey.
Diagnoses and prescriptions for patients managed during a free health care day in Eldoret, Kenya.
Diagnoses and prescriptions for 2,218 patients seen during a "Free Health Care Day" in a semi-urban African town were reviewed. There was a marked tendency to over-prescription, coupled with a failure to use available laboratory tests to diagnose conditions such as malaria and intestinal parasites. Only 37 of 413 patients with malaria had a diagnostic blood smear (17 positive, 20 negative) done. Nevertheless, many patients without any clear diagnosis received multiple drugs. The mean number of drugs prescribed was two; and three or more drugs were prescribed for 677 (33%) patients. The adverse pharmacological and financial aspects of excessive drug prescription are stressed in this communication.
Child↗
Management of malaria before and after introduction of a treatment protocol at the Eldoret District Hospital.
A prospective study on the management of suspected malaria using a protocol on a general medical ward during the months of February and March, 1992 was done and the results compared with those of a retrospective study covering the months of November and December, 1991. The retrospective analysis showed that 78 (65%) from a total of 120 patients received antimalarial drugs despite negative or absent blood smears for malarial parasites. In 41 (34%) of the 120 patients, the first line treatment given was quinine. In the prospective study the overall quinine use dropped sharply to 19% from 54% in the retrospective study. 94 (49%) from a total of 193 patients with suspected malaria had negative blood smears of whom only 8 (4%) received quinine while 63 (33%) did not receive any antimalarial therapy and 38 of these 63 patients ended up with different final diagnoses; the remaining 25 were observed on no antimalarial treatment and discharged home feeling well. These results emphasize the need for proper diagnosis of malaria and suggest that chloroquine is still acceptable and effective as a first line drug for proven cases of malaria in adult patients in Eldoret. Unnecessary quinine use is discouraged as the drug is more expensive with more toxic effects compared to chloroquine.
Adult↗
Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease.
Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.
Adrenal Cortex Hormones↗
Nasal intermittent positive pressure ventilation in acute exacerbations of chronic obstructive pulmonary disease--a preliminary study.
Ten patients (two male) suffering from acute exacerbations of long-standing chronic obstructive pulmonary disease and admitted in hypoxic, hypercapnic respiratory failure were treated with Nasal Intermittent Positive Pressure Ventilation (NIPPV) plus supplemental oxygen, on a general medical ward. The median (range) pH on admission was 7.30 (7.20-7.35), the median age was 67 years (47-77) with an FEV1 (percent of predicted) of 30 (17-39). On admission the median arterial oxygen tension (PaO2) was 4.71 kPa (3.45-6.26) on air, and the carbon dioxide tension (PaCO2) was 7.68 kPa (6.85-9.83). With controlled oxygen therapy there was no significant improvement in PaO2, but the median PaCO2 increased significantly to 9.75 kPa (7.04-11.70) (P < 0.05). By using NIPPV with supplemental oxygen it was possible to significantly improve the median PaO2 to 11.25 kPa (6.70-26.90) (P < 0.01) without worsening PaCO2 levels (8.96 kPa; 6.85-13.10). NIPPV was applied by a senior, respiratory physiotherapist and used intermittently depending on patient tolerance and clinical response. The median total time on NIPPV was 27 h, delivered over 1-5 days. One patient found the mask difficult to tolerate beyond a short period of time. NIPPV was well accepted on a general ward by nursing staff. Three patients later died with progressive hypercapnia, despite an initial response; with one of these patients also receiving intubation and mechanical ventilation. A further patient also received intubation and mechanical ventilation and was eventually discharged. NIPPV plus supplemental oxygen offers a method to correct hypoxaemia on a general medical ward without worsening hypercapnia for acute on chronic, hypoxic, hypercapnic respiratory failure, and warrants further investigation.
Acute Disease↗
Malaria: impact of a standardized protocol on inpatient management.
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Chloroquine↗
Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung disease.
1. Mast cell activation in the lung was investigated by measuring concentrations of mast cell tryptase and histamine in the bronchoalveolar lavage fluid from patients with bronchial carcinoma, sarcoidosis, extrinsic allergic alveolitis or cryptogenic fibrosing alveolitis and from normal subjects. 2. Histamine concentrations in bronchoalveolar lavage fluid supernatants were elevated in the bronchial carcinoma and cryptogenic fibrosing alveolitis groups, and were correlated with the histamine content of the cells recovered. 3. An avidin-biotin-enhanced antigen-capture e.l.i.s.a., using polyclonal rabbit antibody specific for tryptase, and mouse monoclonal antibody AA5, allowed the quantification of tryptase in all samples of bronchoalveolar lavage fluid. Tryptase concentrations were increased in the bronchial carcinoma and extrinsic allergic alveolitis groups and in some of the patients with sarcoidosis, and the levels correlated with mast cell numbers and also with concentrations of albumin. 4. There was no significant correlation between levels of tryptase and histamine, suggesting differences in the rates of metabolism or different cellular sources. 5. The tryptase and histamine concentrations measured suggest that there is continuous degranulation of mast cells within the normal lung, but that this process is more pronounced in patients with bronchial carcinoma or interstitial lung disease.
Adult↗
Histochemical heterogeneity of human mast cells: disease-related differences in mast cell subsets recovered by bronchoalveolar lavage.
Fixation and staining characteristics were studied for mast cells recovered by bronchoalveolar lavage from 67 patients being investigated for lung disease. The number of toluidine blue stained mast cells in formaldehyde-fixed cytocentrifuge preparations was consistently less than in specimens fixed in Carnoy's solution, though the counts were highly dependent on the period of fixation or staining. The cellular histamine content closely correlated with total mast cell numbers in bronchoalveolar lavage fluid, but was not related to the relative proportions of mast cells which were sensitive or resistant to formaldehyde fixation when using a standard protocol. Compared with normal subjects, the numbers of formaldehyde-sensitive mast cells were significantly elevated in patients with bronchial carcinoma, sarcoidosis, extrinsic allergic alveolitis, cryptogenic fibrosing alveolitis, and mycobacterial infection and were particularly high in the cases of interstitial lung disease. An even greater increase in numbers of formaldehyde-resistant mast cells was observed in the patients with sarcoidosis and extrinsic allergic alveolitis. The associations of these mast cell subsets with disease may reflect relationships between the expansion of the formaldehyde-sensitive population and lymphocyte infiltration and between proliferation of formaldehyde-resistant mast cells and tissue fibrosis.
Acetates↗
Tracheal stenosis due to relapsing polychondritis in rheumatoid arthritis.
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Adult↗
Lymphocytic interstitial pneumonia identified as lymphoma of mucosa associated lymphoid tissue.
The widespread interstitial pulmonary infiltration in two patients, showing the clinical, radiological and histological features of lymphocytic interstitial pneumonia (LIP), has been characterized by histological and immunological criteria as malignant lymphoma of follicle centre cell (FCC) origin with plasmacytic differentiation. One patient also had malignant lymphoma of the parotid glands which had been present for many years and was previously considered benign (benign lymphoepithelial lesion). The other patient had a long history of Sjögrens syndrome. The lymphomas in these patients are presented as typical examples of malignant lymphoma of mucosa-associated lymphoid tissue.
Aged↗
Mast cell and histamine content of human bronchoalveolar lavage fluid.
Bronchoalveolar lavage was performed in 97 patients including control patients with bronchial carcinoma (24) and patients with sarcoidosis (20), cryptogenic fibrosing alveolitis (9), and asthma (4), and others. Cytocentrifuged slides were stained by two methods: May-Grünwald Giemsa and toluidine blue. In the last 32 subjects the bronchoalveolar lavage fluid was separated into supernatant and cell pellet for the subsequent assay of the performed mast cell mediator, histamine. Comparison of the two methods of staining showed a bias towards toluidine blue. Controls had a differential mean (SE) mast cell count of 0.07% (0.01%). Higher counts were noted in cryptogenic fibrosing alveolitis--0.61% (0.15%) (p less than 0.001)--and in sarcoidosis--0.14% (0.02%) (p less than 0.05). There was a strong correlation between absolute mast cell counts and cell lysate histamine concentration (r = 0.78, p less than 0.001). Less strong, significant, correlations between supernatant histamine concentration and absolute mast cell counts (r = 0.48, p less than 0.01) or cell lysate histamine concentration (r = 0.72, p less than 0.01) were also found. Derived mean values of histamine per mast cell ranged from 3.7 to 10.9 picograms. The mean histamine content of lavage fluid supernatant as a percentage of the total lavage fluid histamine was 24.9% (3.3%). The possible clinical significance of these findings is discussed.
Adult↗
Side effects of desensitization for allergy--a general practice survey.
Following the unexpected death from acute anaphylaxis of a patient receiving house dust mite desensitization, general practitioners throughout Hampshire were asked about their experience of desensitization and its side effects, by means of a questionnaire. From a total of 695 doctors, 452 (65 per cent) returned valid questionnaires. Sixty-three doctors (14 per cent) did not use desensitization at all, while 20 (4 per cent) used more than 20 courses per year, mainly for patients with hay fever. The majority of doctors were modest prescribers of five or less courses per year of any one preparation. Apart from the fatal case which stimulated this enquiry, one other death was reported.
Anaphylaxis↗
Immunoglobulin E decapeptide-induced 5-hydroxytryptamine release from rat peritoneal mast cells. Comparison with corticotropin-(1-24)-peptide, polyarginine, polylysine and antigen.
A synthetic basic decapeptide from the C4 domain of human immunoglobulin E, corticotropin-(1-24)-peptide, polyarginine and polylysine stimulated up to 90% net release of 5-hydroxytryptamine from mast cells in rat peritoneal-cell suspensions. Concentration-response curves to all four polypeptides were parallel. Polyarginine and polylysine (EC50 congruent to 0.05 microM) were approximately 100-fold more potent than immunoglobulin E decapeptide and corticotropin-(1-24)-peptide (EC50 congruent to 5 microM). Polypeptide-induced release was complete within 5-10s. Immunoglobulin-E-decapeptide-induced 5-hydroxytryptamine release was additive to that induced by low concentrations of polyarginine, but non-additive to that induced by high concentrations of polyarginine. In contrast, release induced by antigen was additive along the whole length of the concentration-response curve to polyarginine. Benzalkonium chloride inhibited immunoglobulin-E-decapeptide- and polyarginine-induced 5-hydroxytryptamine release but enhanced release induced by immunological stimulation.
Animals↗
Inhibition of human lung mast cell sensitization by IgE in allergic sera.
Passive sensitization of mast cells in human lung tissue by antigen-specificity IgE was inhibited by allergic sera containing IgE of other specificities.IgE-free sera and heat-treated sera failed to inhibit. Inhibition by purified myeloma IgE was quantitatively similar to that produced by serum IgE. It is concluded that IgE antibodies of different antigen specificity at concentrations found in allergic sera compete for cell surface receptors on human mast cells.
Antibody Specificity↗
The number and affinity of IgE receptors on dispersed human lung mast cells.
Mast cells obtained by fragmentation of human lung tissue retained the capacity to bind IgE and to respond to immunological challenge. Direct binding studies with radiolabelled IgE enabled quantification of binding parameters of the reaction between IgE and its receptor on human mast cells. The average equilibrium constant was estimated as 1.0 x 10(8) M -1 and the average number of IgE receptors per mast cell as 1.3 x 10(5).
Antibody Affinity↗
Diseases causing cough.
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Bronchial Diseases↗
Antibody responses in self-infections with Necator americanus.
Antibody responses were measured in a volunteer infected four times with Necator americanus over a 27-month period. The main source of antigen was culture fluid in which living adult N. americanus had been maintained for several days. Antibodies to worm acetylcholinesterase and IgE antibodies were detected only with this material, but antibodies were identified by the enzyme-linked immunosorbent (ELISA) assay, with either adult worm secretions or extracts of third-stage infective larvae. The total serum IgE level fell after the first infection, but although it then increased during subsequent infections, it never rose above 600 U per ml. None of the antibody responses suppressed the rat of worm development to maturity, or reduced the fecundity of the parasites. However, it is suggested that the development of the immune response may be associated with the waning of the severe gastro-intestinal symptoms which were experienced in this infection, and which are frequently characteristic of hookworm infections.
Acetylcholinesterase↗
Differences in binding affinity of human IgE for receptors in chopped human lung.
Experiments were performed to ascertain whether IgE in different allergic sera had the same or different sensitizing properties for chopped human lung. When allergic sera were allowed to compete with myeloma IgE for tissue receptors in chopped lung and subsequently challenged with antigen, two groups of sera could be distinguished, one which competed well with myeloma IgE and one which competed poorly. Sera that competed well with myeloma IgE were also able to sensitize for greater histamine release relative to IgE concentration when sensitized lung tissue was challenged with anti-IgE. The converse was true of those sera that competed poorly with myeloma IgE in the antigen assay, in that they sensitized for histamine release only at relatively high IgE concentrations in the anti-IgE assay. The possible significance of these findings is discussed.
Antibody Affinity↗