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Biomedical subjects

F Alexander

Publications and source records attributed to F Alexander.

At least 37 records · Page 2Linked to original sources

Peri-operative jejunostomy-tube feeding in reconstructive spinal surgery.

Eight malnourished children with neuromuscular spinal deformity were treated with jejunostomy tubes for supplemental feeding to attain appropriate weight before reconstructive surgery. All patients had significant gastro-esophageal reflux and had failed to gain weight during an eight-month oral supplementation program. There were no complications associated with the placement or use of the jejunostomy feeding tubes and all patients gained weight in a safe and predictable fashion, had successful spinal fusion and have maintained satisfactory weight at follow-up. Jejunostomy feeding is a safe and effective method of correcting malnutrition in patients with spinal deformity which precludes gastrostomy and Nissen fundoplication.

Adolescent

The pattern of childhood and related adult malignancies near Kingston-upon-Hull.

A study of childhood malignancies in North Humberside for 1974-1986 has revealed significant spatial aggregations. Though no specific reason was found, certain geographical areas, tumour groups and putative risks were identified for further study. One possible risk was a tin smelter to the west of Hull. A new method of analysis (Stone's conditional Poisson maximum) was used and showed some evidence of increased risk close to the smelter. This was accounted for by the solid tumours (primarily central nervous system malignancies) and was not apparent for the leukaemias. The Poisson maximum method is a special case of isotonic regression; a more general isotonic regression method, also due to Stone, Maximum Likelihood Ratio (MLR), is also available, and for reasons described elsewhere we prefer the more general method. The present study begins by applying this to the childhood data and then to data for corresponding adult disease (leukemias and central nervous system tumours) in the same area and time period. In both children and adults the results are negative for the leukaemias. For the remaining tumour categories, there is a significant increase in risk close to the smelter, but it is not possible to identify any aspect of the smelter or feature in its vicinity as causative.

Adolescent

Joining the staff.

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Education, Nursing

Investigation of spacial clustering of rare diseases: childhood malignancies in North Humberside.

STUDY OBJECTIVE: The aims of the study were (1) to test for uniformity of distribution of childhood leukaemias and other malignancies; and (2) to consider the aetiological implications of unusual distributions. DESIGN: A test for spacial clustering was applied using a method which allows for unequal distribution of the population at risk and avoids using census data to provide population denominators. When clustering was identified, four possible aetiological links which had already been suggested to the Leukaemia Research Fund Centre were examined in a local area. SETTING: The study was carried out in the Yorkshire Health Region in the north of England. PATIENTS: 144 children under 15 years of age with a diagnosis of malignant disease known to the Yorkshire Regional Childhood Tumour Registry between 1974 and 1986 were included in the analysis. Of these 53 had leukaemias and nine had lymphomas. MEASUREMENTS AND RESULTS: Significant localised clustering was found in North Humberside, though not in the whole of the Yorkshire Health Region. A number of clustered cases were identified, some of whom were in a post code sector, Hull 10, to the west of Kingston-upon-Hull, about which concern had been expressed since 1985. There was however no evidence that disease clustering was confined to this area. Four previously suggested hypotheses about causation in this particular area were examined but the results were negative or inconclusive. CONCLUSIONS: The identification of spacial clustering must be seen as only the first step in a series of investigations; it can only rarely lead to aetiological conclusions by itself, but it can motivate and target other investigations.

Adolescent

Chronic myeloid leukaemia in Yorkshire: a case control study.

The results of a case-control study of chronic myeloid leukaemia in adults are reported. 122 cases and 241 controls were interviewed. Excess risks associates with heart disease and related drugs were revealed. In addition a weak association with occupational and/or hobby exposure to irradiation emerged.

Case-Control Studies

Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine.

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.

Analysis of Variance

Correlation of infertility with altered tubal morphology and function in mice with salpingitis induced by a human genital-tract isolate of Chlamydia trachomatis.

Progesterone-treated C3H mice were inoculated into the uterus or ovarian bursa with a human genital tract isolate of C. trachomatis (serovar E), or with control medium alone. The mice were then observed at various times up to 260 days after inoculation. Before being killed the mice were given pituitary gonadotrophins to induce ovulation. Eggs were sought in the oviducts and ciliary activity in the fimbrial and ampullary sections of the oviducts was determined by light microscopy, before detailed examination by scanning electron microscopy. Eggs were visible in all control oviducts and both mucosal ultrastructure and ciliary activity appeared normal. By contrast, eggs were not recovered from the inoculated oviducts of mice infected intrabursally, nor was ciliary activity observed up to 28 days after inoculation. After this, ciliary activity reappeared but eggs were still not transported to the oviduct. Ultrastructural studies suggested that severe mucus congestion accompanied by tubal oedema and loss of ciliated epithelia play a major role in the aetiology of chlamydial-induced tubal damage. Infertility following chlamydial salpingitis could be associated with failure of egg transportation to the oviduct. Egg transport was still impaired even when luminal ciliary activity, ultrastructural integrity and patency had recovered. Our results suggest that chlamydial salpingitis in this mouse model closely resembles the human disease in its pathology and consequences for fertility, making the model particularly relevant for research on chlamydial vaccine development.

Animals

Characterization of skin lesions in mice following intradermal inoculation of Haemophilus ducreyi.

Twelve strains of H. ducreyi, which included two reference strains, were each inoculated intradermally into the flanks of CBA mice. All strains produced self-limited lesions which were macroscopically and microscopically typical of those seen in chancroid. Pustular nodules, about 5mm in diameter, developed at all inoculation sites by the second day when 10(7) organisms were inoculated. Approximately half of these lesions ulcerated and all had regressed by 2 weeks. Smaller nodules developed at about half the sites from the second to the fifth day when 10(6) or 10(5) organisms were given, but these did not ulcerate. No lesions were seen when 10(3) organisms were inoculated. Organisms were recovered from the lesions up to 11 days after inoculation. Specific H. ducreyi antigen, sought by a monoclonal antibody test, was detected in lesions up to 15 days following inoculation. Heat-killed organisms of H. ducreyi also produced nodules and ulcers although these were slightly smaller than those which developed after inoculation of viable bacteria. Similar lesions to those caused by H. ducreyi were produced after intradermal inoculation of about 10(8) viable or killed Neisseria gonorrhoeae organisms. Treatment of mice with ceftriaxone had little or no effect on the subsequent development of H. ducreyi-induced lesions. These findings indicated that the lesions were not produced specifically by viable H. ducreyi organisms. Ulcers were also produced following intradermal inoculation of purified lipopolysaccharide (LPS) from H. ducreyi or N. gonorrhoeae, but not by cell-free filtrates prepared from H. ducreyi cultures indicating a possible role for LPS in the pathogenesis of ulcerative skin lesions.

Animals

Severity of salpingitis in mice after primary and repeated inoculation with a human strain of Chlamydia trachomatis.

Groups of inbred female mice of strains CBA or C3H were infected genitally with a pathogenic human strain of Chlamydia trachomatis (N.I.1, serovar F) known to produce salpingitis and infertility in mice. Mice were inoculated under the ovarian bursa or directly into the uterine cavity with chlamydiae (test groups) or with sucrose-phosphate transport medium (control groups) before being challenged with chlamydiae by the same route 12-17 weeks later. Twenty-five pairs of test and control animals were killed from 7 to 77 days after challenge and oviductal inflammatory changes, recovery of organisms, and antibody responses were compared in the two groups. Salpingitis in the mice infected previously (tests groups) was more severe than in the controls in 56% of comparisons, the same in 24% and less severe in 20%. However, despite the increase in the severity of disease, shedding of C. trachomatis from the lower genital tract was less prolonged after rechallenge or did not occur. Salpingitis occurred in spite of the almost certain presence of pre-existing serum antibody, and accelerated and accentuated antibody response in the rechallenged mice. Furthermore, the continued existence of high titres of antibody was not associated with less severe disease. Thus, the results reveal that previous exposure to chlamydiae does not prevent salpingitis and suggest that its severity is influenced by cell-mediated immune mechanisms.

Animals

Natural history of in situ breast cancer in a defined population.

The entire experience of in situ breast cancer in Alberta from 1953 to 1984 was examined. Of 243 patients coded, 226 were available for review by a panel of three pathologists. In 149 cases the diagnosis of in situ disease was confirmed. One hundred and eight patients had 109 ductal carcinomas in situ, 38 patients had lobular carcinomas in situ, with 3 patients having both. A multitude of treatments was used, ranging from local excision to radical mastectomy. Survival at a mean of 6 years follow-up was equal in all groups, with only two patients with a confirmed diagnosis of ductal carcinoma in situ dying from clinically suspected systemic disease. In patients treated by local excision, ipsilateral cancers were seen in 12% of ductal carcinoma in situ patients who had local excision and 13% of patients with lobular carcinoma in situ. Contralateral metachronous invasive cancers were seen in 6% of ductal carcinoma in situ patients and 3% of lobular carcinoma in situ patients. No lymph node involvement was seen in any of these patients, either with prophylactic dissection or in follow-up. The conclusion reached was that both in situ lesions are similar in their clinical course. Lymph node dissection is not necessary. Pathologic review is critical for accurate studies, with a change in diagnosis of 36% of diagnoses. Treatment does not appear to affect prognosis. The most appropriate treatment needs to be determined in prospective randomized trials.

Adult

Randomisation by cluster and the problem of social class bias.

For randomised population trials the unit of randomisation is normally the individual person. In some situations, however, investigators take other groups as basic unit and one such design is cluster randomisation. Considerable attention has been given to this design recently in statistical and epidemiological literature. The Edinburgh randomised trial of breast cancer screening is an example which takes general practices as clusters of patients. The experience of this trial is reported here. Mortality from all causes, cardiovascular disease and lung cancer over the first 5 year period of follow up are examined. We found that spurious mortality differences were present in the analyses, which do not allow for socio-economic status. From examination of methods of adjusting for this, we conclude that allowance can be made at the analysis stage, and it is intended that this approach will be adopted when breast cancer mortality is analysed in the Edinburgh trial. Nevertheless, we recommend that for future studies with outcome related to socio-economic status, randomisations which use this design be stratified by socio-economic criteria where this is feasible.

Bias

Corticosteroid treatment and prognosis in pulmonary eosinophilia.

The acute and long term responses to corticosteroid treatment in 65 patients with pulmonary eosinophilia have been reviewed. Of the 247 episodes of pulmonary eosinophilia that were documented during a median follow up period of 14 years, 186 were treated with prednisolone. Complete clearing of chest radiographic infiltrates occurred in 65% of the 247 episodes, partial clearing in 25%, and no response in 9%. Blood eosinophil counts were monitored during 194 episodes and returned to normal in 72%, decreased in 19%, and remained raised in 9%. Complete radiological clearing and a reduction in blood eosinophil counts were more common in episodes treated with prednisolone. Long term prednisolone was given to 28 of the 33 patients with allergic bronchopulmonary aspergillosis (mean 7.4 mg/day for 11 years) and to 29 of the 32 "non-aspergillosis" patients (mean 8.1 mg/day for 4.6 years). Initial pulmonary function, measured between episodes, was worse in patients with allergic aspergillosis than in those without (mean % predicted: FEV1 57% v 83%, vital capacity (VC) 76% v 88%). During a mean follow up period of 12 years neither group displayed further decline in FEV1 or VC.

Acute Disease

In vitro activity of eight antimicrobial agents against non-penicillinase-producing gonococci isolated in Munich.

The susceptibility of 119 strains of Neisseria gonorrhoeae isolated in Munich in 1986 to eight antibiotics was assessed. Although some degree of resistance to penicillin and tetracycline, as well as high minimum inhibitory concentrations (MIC) of spectinomycin, were observed, all the strains were sensitive to ciprofloxacin, enoxacin, fleroxacin, cefotaxime, and FCE 22250.

Anti-Bacterial Agents