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Biomedical subjects

N H Anderson

Publications and source records attributed to N H Anderson.

14 recordsLinked to original sources

The enantiomeric resolution of ciprofibrate and related compounds by HPLC using chiral stationary phases.

The attempted chromatographic resolution of the drug ciprofibrate and a range of related compounds, containing the chiral moiety 2,2-dichlorocyclopropylbenzene, using five different chiral stationary phases is described. Aqueous mobile phases were used throughout and the successful separation of nine out of 12 pairs of enantiomers was achieved. Structures remote from the chiral centre were seen to affect chiral recognition.

Cellulose

Photostability testing of drug substances and drug products in UK pharmaceutical laboratories.

Results of a survey on photostability testing of drug substances and products by UK pharmaceutical laboratories are presented. The results indicate diverse practices in the form of presentation of the product and particularly in exposure to light (as measured in lx days), although there was more consistency in analytical methods and in the analytical criteria used to classify products as stable or unstable for those laboratories adopting this type of classification. A majority of laboratories use daylight in addition to artificial light sources for tests on drug substances and products. Artificial daylight fluorescent tubes and xenon lamps are the most widely used sources of artificial light and both should provide a reasonable simulation of natural light. All laboratories intend their photostability tests to represent light exposure which exceeds that expected to occur in practice but the tests actually applied vary widely in severity as shown in the wide range in light exposure (8-4500 klx days). Therefore the classification of products as stable or unstable needs to be considered carefully in relation to the severity of the test used. Testing procedures for drug substances are broadly similar to those used for drug products. It is concluded that the variation in testing procedure is the result of differing perceptions regarding product exposure in practical usage and the absence of regulatory guidelines.

Drug Industry

Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study.

Goblet cell carcinoids are uncommon but distinctive tumours of the appendix. We have reviewed 11 cases diagnosed within the period 1976-1990. The mean age at presentation was 58 years (range 24-76), with a female:male ratio of 8:3. At presentation, in seven patients tumour was confined to the appendix or mesoappendix (mean age 51) and in four there was extension beyond the appendix (mean age 69). Of the seven patients with localized tumour, six are alive and without clinical disease after a mean follow-up period of 32 months and one died with recurrent tumour after 10 years. Of the four with more extensive disease, two died during follow-up (at 23 months with probable liver metastases and at 16 months with intestinal obstruction) and two are alive, one with disease and one clinically disease-free. Immunohistochemistry showed that all of the tumours stained positively for either neuron-specific enolase, chromogranin A or protein gene product 9.5. No tumour stained with antiserum to substance P and none showed glucagon-like immunoreactivity, but four cases stained positively for pancreatic polypeptide, an unusual feature in midgut carcinoids.

Adult

Use of the autopsy in Northern Ireland and its value in perioperative deaths.

A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group.

Adolescent

Diode array detection of low level co-eluting species in high-performance liquid chromatography.

A simple and sensitive method for detecting low levels (0.5 and 1.0%, w/w) of co-eluting species in HPLC has been developed. This method is based on the subtraction of normalized peak up-slope and down-slope spectra from that of the apex. Visual inspection of the resultant "difference spectra" allows for a qualitative judgement regarding the integrity of the peak under consideration.

Antazoline

Value of the necropsy in perioperative deaths.

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths.

Adolescent

Necropsies in clinical audit.

The need for specialised forms of clinical audit was highlighted by the report of the Confidential Enquiry into Perioperative Deaths (CEPOD). Necropsy rates in a Northern Ireland teaching hospital were studied with particular reference to perioperative deaths. To provide an overall context for these observations, the pattern of the necropsy services in Northern Ireland as a whole was also determined. For 600 consecutive deaths in a major teaching hospital, the overall necropsy rate was 180 (30%). In the 74 perioperative deaths in this group (as defined by the CEPOD) the necropsy rate was 26 (35%), compared with 16 out of 72 (22%) for other surgical deaths and 89 out of 386 (23%) for medical cases. More coroners' necropsies were carried out in the perioperative group. These figures are within the range of the CEPOD experience. In 1987, in the whole of Northern Ireland, there were 8859 hospital deaths, 520 (5.9%) hospital necropsies, and 516 (5.8%) coroners' necropsies, giving an overall necropsy rate of 11.7%. Outside the two major Belfast teaching hospitals, however, there were 6799 hospital deaths, 76.6% of all hospital deaths for Northern Ireland. In this group there were 180 (2.6%) hospital necropsies and 383 (5.6%) coroners' cases, the overall necropsy rate being only 8.2%. These wide variations reflect the fact that the number of pathologists in post in the peripheral areas of the province falls substantially short of levels recommended by the Royal College of Pathologists. If clinical audit along CEPOD lines is to be effective nationally, more emphasis should be placed on the value of necropsy and local deficiencies in provision will have to be identified and remedied. It is suggested that this could be achieved by combining audit provisions with budgetary incentives.

Autopsy

Comparative judgment: tests of two theories using the Baldwin figure.

Two theories of comparative judgment were compared across four experiments on their ability to explain the Baldwin figure, a focal line whose apparent length is affected by square boxes at or near its endpoints. Left-box size, right-box size, line length, line-box distance, and other variables were varied in factorial designs to allow application of functional measurement methodology. The model from adaptation level theory did poorly in several respects. In particular, it had trouble with the pervasive lack of contrast. Further, it could not account for the fact that a box added contralaterally increased the illusion, whereas the same box added ipsilaterally decreased the illusion. The model from information integration theory did substantially better, though it too had trouble with some of the results. An alternative interpretation was suggested in which the Baldwin figure is viewed as a positive context or assimilation effect. This positive context formulation may generalize to other illusions, such as those produced by the Müller-Lyer and Ponzo figures.

Attention

Assessment of chromatographic peak purity of drugs by multivariate analysis of diode-array and mass spectrometric data.

Numerous multivariate chemometric approaches have been developed for LC-UV data acquired using a diode-array detector (DAD), but these methods have not been widely exploited for LC-MS data. Principal component analysis (PCA) and subsequent axis rotation within the reduced factor space are assessed for LC-DAD and LC-MS data as approaches for estimating the number of components (i.e. the rank of the data) under a single chromatographic peak for compounds whose UV-spectra are very similar. Multivariate techniques for LC-DAD data are shown to suffer from inherent limitations of sensitivity for the minor components. The novel technique in LC-MS of plotting the rotated PCA data in two-dimensional factor space generates characteristic ion clusters, giving a visual criterion of peak purity. Single ion chromatograms produced subsequently confirm the profile of each coeluting component and give evidence of the degree of peak overlap. The application of this new chemometric technique to the detection of low levels of coeluting impurities by LC-MS is discussed as a novel approach for the validation of LC separations in pharmaceutical research and development.

Chromatography, Liquid