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Biomedical subjects

P M Kelly

Publications and source records attributed to P M Kelly.

At least 37 records · Page 2Linked to original sources

Solitary fibrous tumour of the prostate.

Solitary fibrous tumours are rare, benign neoplasms that are most commonly found in the pleura and less commonly on other serosal surfaces. Their cell of origin and aetiology are uncertain. A case of solitary fibrous tumour of the prostate is presented. We believe this to be the first case of this lesion to arise in this gland. Solitary fibrous tumours of the prostate may be confused with granulomatous prostatitis or carcinoma as all three may present with a nodule on rectal examination and appear as a hypoechoic nodule on transrectal ultrasound.

Humans↗

Antibiotic susceptibility of potentially probiotic Lactobacillus species.

In recent years, the time-honored reputation of lactobacilli as promoters of gastrointestinal and female urogenital health has been qualified. This has occurred due to a rare association with human infection in the presence of certain predisposing factors and their potential to act as a source of undesirable antibiotic resistance determinants to other members of the indigenous microbiota. This necessitates greater caution in their selection for use in microbial adjunct nutrition and disease management (prophylaxis and therapy). It was against this background that 46 Lactobacillus strains from human and dairy sources were assayed for susceptibility to 44 antibiotics. All strains were resistant to a group of 14 antibiotics, which included inhibitors of cell wall synthesis (cefoxitin [30 microg] and aztreonam [30 microg]), protein synthesis (amikacin [30 microg], gentamicin [10 microg], kanamycin [30 microg], and streptomycin [10 microg]), nucleic acid synthesis (norfloxacin [10 microg], nalidixic acid [30 microg], sulphamethoxazole [100 microg], trimethoprim [5 microg], co-trimoxazole [25 microg], and metronidazole [5 microg]), and cytoplasmic membrane function (polymyxin B [300 microg] and colistin sulphate [10 microg]). All strains were susceptible to tetracycline (30 microg), chloramphenicol (30 microg), and rifampicin (5 microg). Four human strains and one dairy strain exhibited atypical resistance to a penicillin, bacitracin (10 microg), and/or nitrofurantoin (300 microg). One human strain was also resistant to erythromycin (15 microg) and clindamycin (2 microg). These resistances may have been acquired due to antibiotic exposure in vivo, but conclusive evidence is lacking in this regard. Seven microorganism-drug combinations were evaluated for beta-lactamase activity using synergy and nitrocefin tests. The absence of activity suggested that cell wall impermeability appeared responsible for beta-lactam resistance. The occurrence of a minority of lactobacilli with undesirable, atypical resistance to certain antibiotics demonstrates that not all strains are suitable for use as probiotics or bacteriotherapeutic agents. The natural resistance of lactobacilli to a wide range of clinically important antibiotics may enable the development of antibiotic/probiotic combination therapies for such conditions as diarrhea, female urogenital tract infection, and infective endocarditis.

Anti-Bacterial Agents↗

Selective detection, enumeration and identification of potentially probiotic Lactobacillus and Bifidobacterium species in mixed bacterial populations.

Lactobacillus and Bifidobacterium species constitute a significant proportion of probiotic cultures used in developed countries in 'microbial adjunct nutrition'. A number of differential plating methodologies have been developed which seek to selectively detect and enumerate these bacterial groups in bioproducts. Differences in oxygen tolerance, nutritional requirements, antibiotic susceptibility, and colony morphology and colour constitute the bases of differentiation in these methods. The choice of methodology depends on the nature of the bioproduct to be examined (wet or dry) and the presence of other bacteria such as starter cultures. In addition, a number of nucleic acid methods have been developed in recent years which enable the specific detection of these bacterial groups at species, subspecies and strain level in mixed populations. The methods use synthetic 16S and 23S rRNA-targeted hybridisation probes, the specificity of which can be adjusted to fit any taxonomic ranking from genus to genotype, for detection, enumeration and identification in situ or after differential plating. The combined use of differential plating and molecular strain typing methodologies provides food and medical microbiologists with a powerful and targeted approach to the detection, enumeration and identification of these bacterial groups and their members in a wide range of food and biological materials. An overview of these methods is presented in this review.

Bifidobacterium↗

Potentiometric, enantioselective sensors for alkyl and aryl ammonium ions of pharmaceutical significance, based on lipophilic cyclodextrins.

Lipophilic alpha, beta and gamma cyclodextrins (CDs) have been systematically analysed in order to establish their selective binding to onium ions. They have been identified as excellent ionophores for a range of ions of vital importance in clinical, pharmaceutical and forensic analysis. From the results obtained we found the following. A peroctylated cyclodextrin provides a size-selective cavity for the binding and detection of onium ions. Potentiometric alpha, beta and gamma cyclodextrin-based electrodes selectively sense NH4+, NMe4+ and NEt4+ ions respectively. These experiments were performed in order to enable us to understand the nature of analyte recognition by the lipophilic cyclodextrins. Peroctylated alpha CD is a suitable ionophore for dopamine hydrochloride, -log[C] = 5.4, -log K = 2.0 (in serum level of Na+, K+, Ca2+) whereas peroctylated and 2,6 didodecyl beta CD sense acetylcholine chloride, -log[C] = 5.0, -log K = 4.2 (in serum level of Na+, K+, Ca2+) and creatinine hydrochloride, -log K = 2.7 (in serum level of Na+, K+, Ca2+), respectively. The 2,6 didodecyl beta CD responds to more bulky aryl ammonium ions such as the anaesthetics procaine, prilocaine and lignocaine hydrochlorides, -log K = 4.2 (in serum level of Na+, K+, Ca2+). Partially octylated alpha CD has been identified as an enantioselective sensor for ephedrine hydrochloride, -log K = 4.5 (in serum level of Na+, K+, Ca2+), -log Kpot+/- = 2.6, and related compounds such as amphetamine hydrochloride. The 2,6 didodecyl beta CD is enantioselective for propranalol hydrochloride, -log K = 4.2 (in serum level of Na+, K+, Ca2+), -log Kpot+/- = 2.7. Complexation has also been studied by electrospray mass spectrometry (ESMS).

Acetylcholine↗

Calculation of overall tilt angles for a double tilt holder in a TEM.

A simple formula has been derived for the tilt angle of a specimen in terms of the two tilt angles of a side entry, double tilt holder in a transmission electron microscope. An expression for calculating the direction of the apparent tilt axis in relation to the observed diffraction pattern has also been derived. The accuracy and reproducibility of specimen tilting has been assessed experimentally.

Mathematics↗

Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is a common immune-mediated drug reaction that can be complicated by life-threatening arterial thrombosis. The diagnosis can be confirmed by demonstrating heparin-dependent release of radiolabeled serotonin from washed normal platelets in the presence of patient serum. However, certain serum samples from these patients produce 14C-serotonin release from some but not other normal donor platelets. We investigated this problem of donor platelet variability by studying the reactivities of 10 serum samples from patients with heparin-induced thrombocytopenia with platelets from 10 normal donors (100 serum and platelet combinations). We observed a marked variability in reactivity for patient serum and platelets from normal donors; this initially appeared random. However, closer examination indicated that the reactivities varied hierarchically. Because heparin-induced thrombocytopenia is caused by binding of heparin-dependent IgG to platelet Fc receptors, we examined whether platelet Fc receptor number or function explained the variability in platelet reactivity. We observed that platelet Fc receptor function, as measured by platelet release associated with heat-aggregated IgG, was highly correlated with platelet reactivity to heparin-induced thrombocytopenia serum samples. No significant correlation, however, was found between Fc receptor number and platelet response. Reaction of murine monoclonal antibodies that activate human platelets by means of the platelet Fc receptors was not predictive of platelet reactivity to heparin-induced thrombocytopenia serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors↗

Soft tissue and visceral sarcomas in Irish patients. A preliminary report from the Dublin Soft Tissue Tumour Panel.

Sarcomas of the soft tissues and viscera are a diverse group of uncommon neoplasms that often present difficult diagnostic and management problems. The Dublin Soft Tissue Tumour Panel prospectively reviewed pathology material from 137 patients of four Dublin teaching hospitals between January 1989 and August 1990. The prevalence of sarcomas in Irish patients was found to be similar to that estimated for the United States. The most common sarcoma of soft tissues was malignant fibrous histiocytoma (14) and the most common visceral sarcoma was leiomyosarcoma (10). The most problematic diagnoses were 3 peripheral neuroepitheliomas (extraskeletal Ewing's sarcomas) which occurred in patients aged 19-27 years, distinctly younger than the typical adult sarcoma patient. Clinical follow-up is in progress and will be combined with the findings of a linked retrospective study, to facilitate evaluation of all aspects of management.

Abdominal Neoplasms↗

Diclofenac associated hepatitis.

Diclofenac is a widely used non-steroidal anti-inflammatory drug, being the most commonly prescribed of its kind in the world. This paper describes five cases of hepatitis with clinical features indicating a direct link with diclofenac. All the patients presented with an acute hepatitis, three being jaundiced. They gave a history of taking diclofenac up to the time of presentation, four of the five having started the drug within the previous 3 months. There were no other features in the histories to suggest alternative causes for the liver dysfunction. Liver function tests were grossly abnormal in all cases, showing a hepatitic picture. A liver biopsy was performed in 4 cases, and showed features of an acute hepatitis with inflammation and hepatocyte damage dominating. The liver dysfunction returned to normal on drug withdrawal in four of the five cases, with full recovery by 3 months. One patient developed steroid-responsive chronic active hepatitis. Hepatotoxicity associated with diclofenac is documented, but previously only a few isolated cases have been described. The occurrence of five cases in one gastroenterology unit over a 12-month period suggests that hepatitis associated with diclofenac may be commoner than previously supposed.

Aged↗

Mass production and purification of Euproctis chrysorrhoea (L.) nuclear polyhedrosis virus.

The rearing of larval Euproctis chrysorrhoea (L.) on an artificial wheatgerm diet is described. The larvae grew well on the diet, but took over ten weeks to complete their development, reflecting their prolonged life-span in the field. Using these larvae it was possible to mass produce a nuclear polyhedrosis virus (NPV) isolated from this species, with a view towards its use as a biological insecticide. A mean of 5.86 x 10(9) semi-pure NPV polyhedral inclusion bodies/g virus-killed larva was produced. The purification method described (simple centrifugation) removed over 99% of contaminant urticaceous hairs. Further purification through a sucrose gradient removed more hairs, but also resulted in a loss of NPV of about 35%.

Animals↗

Kupffer cell number is normal, but their lysozyme content is reduced in alcoholic liver disease.

A quantitative immunohistochemical study of Kupffer cells in liver biopsies from alcoholics was carried out. Two markers were compared, lysozyme and an antimacrophage monoclonal antibody EMB/11. The results showed that there is no significant reduction in Kupffer cell numbers in acute and chronic alcoholic liver disease but that there is a reduction in the number of Kupffer cells staining positively for lysozyme. Thus, those clinical phenomena such as endotoxaemia in alcoholic liver disease are not due to reduction in Kupffer cell number but perhaps to a functional deficit in these cells.

Antibodies, Monoclonal↗

Peripheral blood and portal tract lymphocyte populations in primary sclerosing cholangitis.

The relative distribution of lymphocyte subpopulations in the blood and liver of patients with primary sclerosing cholangitis (PSC) and related diseases has been studied using immunoenzyme techniques. The peripheral blood CD4/CD8 T lymphocyte ratio was significantly higher in active ulcerative colitis (UC) and in PSC with inactive UC than in inactive UC alone. In contrast, no relationship with disease activity was seen in Crohn's disease. The portal tract t lymphocyte count per high power field (mean +/- S.D.) was higher in pre-cirrhotic PSC (173 +/- 105) and primary biliary cirrhosis (PBC: 210 +/- 110) than in histologically normal liver (42 +/- 27). However, the overall portal tract CD4/CD8 ratio was similar in PSC (1.49), PBC (1.89) and normal controls (1.63). The results are consistent with immunological involvement in the pathogenesis of PSC, but argue against the hypothesis that changes in the peripheral blood T cell subsets are due to sequestration at the site of tissue inflammation.

Adolescent↗

Separation of amphotericin B components by combined thin-layer and high-performance liquid chromatography.

Amphotericin B has been separated into five components by the use of thin-layer chromatography (TLC) with only methanol as the developing solvent. Each TLC component was then subjected to high-performance liquid chromatography. Besides the two major components found in other studies, amphotericin B was also found to contain five other significant heptaenes, one tetraene, two fluorescent polyenes (pentaene and heptaene), and at least five other significant components which had appreciable absorbance at approximately 305 nm. In addition, amphotericin B was found to exhibit as in a previous study by other workers, only a trace amount of fluorescence.

Amphotericin B↗

Macrophages in human breast disease: a quantitative immunohistochemical study.

We describe a quantitative histological study of 34 breast biopsies using a marker for human macrophages, the monoclonal antibody EBM/11. Seventeen of the biopsies were of malignant tumours. Both benign and malignant breast tissue contained large numbers of macrophages with significantly higher numbers occurring in the malignant group. An analysis was made of macrophage counts according to stage, grade and prognostic index of the malignant tumours. There was no correlation between macrophage numbers and any of these parameters in malignant breast tumours. We discuss the possible reasons why some earlier studies (using other markers such as lysozyme), have shown an apparently insignificant number of intratumoral macrophages.

Adult↗

Granular cell tumours revisited. An immunohistological and ultrastructural study.

Twenty-five granular cell tumours were stained with a panel of antibodies to histiocytic, muscle, neural, neural crest, epithelial and endothelial markers. Electron microscopy was also performed in six cases. Twenty-four of the cases were similar morphologically and immunocytochemically. One case with features of an endothelial origin is described. The present study strongly supports the viewpoint that granular cell tumours are a distinct entity rather than being the common appearance of a group of lesions of differing histogenesis. Origin from a neural crest-derived peripheral nerve-related cell is favoured.

Humans↗

Expression of HLA-DR antigens on bile duct epithelium in primary sclerosing cholangitis.

The expression of HLA class I (HLA-A, B, C) and class II (HLA-DR) antigens on the biliary epithelium of 10 patients (nine men) with primary sclerosing cholangitis (PSC) was investigated using an immunoperoxidase technique on cryostat sections. Five patients were staged as grade II and five grade III on hepatic histology. None were cirrhotic. as grade II and five grade III on hepatic histology. None were cirrhotic. Controls were nine patients with primary biliary cirrhosis (PBC), five with extra hepatic biliary obstruction, 15 with other forms of chronic liver disease and six with normal livers. Bile ducts from the normal subjects and patients with chronic liver disease did not express HLA-DR antigens. In contrast, all 10 of the PSC biopsies showed varying degrees of HLA-DR staining of the biliary epithelium. Expression of DR antigens was also found on the bile ducts of all five patients with extra hepatic biliary obstruction and in six of nine patients with PBC. Expression of HLA class I antigens was seen on the biliary epithelium of all the biopsies examined. Increased numbers of helper and suppressor T-cells were seen in the portal tracts of all the PSC patients. This study has confirmed that aberrant expression of HLA-DR may occur on the biliary epithelium of some, but not all, patients with PBC. In addition, the study has shown that aberrant expression of HLA-DR always occurs in PCS at an early stage of histological liver damage. While this may be important in the pathogenesis of PSC, the aberrant expression in extra hepatic biliary obstruction suggests that it may be a secondary phenomenon.

Adult↗

EBM/11 reactivity in malignant histiocytosis.

A patient presented initially with a testicular mass, which on biopsy had morphological features consistent with malignant histiocytosis. The tumour cells labelled strongly with EBM/11, a murine monoclonal antibody with high specificity for cells of the human mononuclear phagocyte system. Subsequent clinical and laboratory studies confirmed the diagnosis. As poorly differentiated tumour cells reacted with EBM/11, this antibody may be useful in positively identifying malignant tumours with histiocytic differentiation from malignancies of other types where morphological detail alone is inconclusive in tumour classification.

Aged↗