PubMed Health⌕ Search

Biomedical subjects

G Tovey

Publications and source records attributed to G Tovey.

At least 19 recordsLinked to original sources
PubMed1999

Shaping the modern pharmaceutical development facility.

The modern pharmaceutical development facility is vastly different from previous designs. In this review, the authors describe the trends and types of facility currently used in the development of pharmaceutical products, and discuss some of the trends that will shape those facilities of the future.

Journal Article↗
PubMed1998

Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture.

Burkholderia pseudomallei causes melioidosis, a serious and often fatal bacterial infection. B. pseudomallei can behave as a facultatively intracellular organism and this ability may be important in the pathogenesis of both acute and chronic infection. The uptake of B. pseudomallei and other Burkholderia spp. by cells in tissue culture was examined by electron microscopy. B. pseudomallei can invade cultured cell lines including phagocytic lines such as RAW264, J774 and U937, and non-phagocytic lines such as CaCO-2, Hep2, HeLa, L929, McCoy, Vero and CHO. Uptake was followed by the intracellular multiplication of B. pseudomallei and the induction of cell fusion and multinucleate giant cell formation. Similar effects were produced by B. mallei and B. thailandensis.

Animals↗
PubMed1998

An ultrastructural study of the phagocytosis of Burkholderia pseudomallei.

Burkholderia pseudomallei causes melioidosis and is believed to be an intracellular pathogen in human and animal disease. The uptake of B. pseudomallei by mouse peritoneal macrophages and cells in tissue culture was examined by electron microscopy. In all the systems studied B. pseudomallei were phagocytosed and apparently inhibited the normal processes of intracellular killing. Destruction of the phagosome membrane occurred and the bacteria escaped into the cytoplasm.

Animals↗
PubMed1997

Thalidomide: a novel therapy for microsporidiosis.

BACKGROUND & AIMS: Microsporidiosis is a common cause of chronic diarrhea in human immunodeficiency virus (HIV)-seropositive individuals and often does not respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as therapy. METHODS: Eighteen subjects with chronic diarrhea caused by Enterocytozoon bieneusi that had not responded symptomatically to albendazole and 1 untreated subject with Encephalitozoon intestinalis received 1 month of thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and body weight, histological response by light microscopy with villus height/crypt depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha level. RESULTS: Seven subjects with chronic diarrhea due to E. bieneusi had a complete clinical response, and 3 had a partial response to thalidomide. There was a significant decrease in stool frequency from 5.3 to 3.1 per day (P = 0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P = 0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent disruption of all stages of the life cycle of E. intestinalis. CONCLUSIONS: Thalidomide may be an effective therapy for diarrhea and weight loss from E. bieneusi.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The ultrastructure of stressed Legionella pneumophila.

Legionellae are able to survive in natural environments which kill many other organisms. The reason for this stress resistance is not well understood nor have its morphological correlates been investigated. The ultrastructure of Legionella pneumophila subjected to stress by heat, acid and starvation, was studied by transmission electron microscopy. Heat-treated cells showed little change although cell shape tended to be distorted. Acid-treated cells showed severe shrinkage of cytoplasmic contents. Starvation caused a reduction in cell size, and after 1 month of starvation cells became fragile, although viability was not reduced.

Acids↗
PubMed1993

Diarrhoea associated with cyanobacterium-like bodies: a new coccidian enteritis of man.

Faecal excretion of cysts known as cyanobacterium-like bodies (CLB) is associated with a diarrhoeal illness, which is often prolonged and severe. It is seen mainly in travellers and immunocompromised patients. Recently these cysts have been shown to be coccidian oocysts. We describe three patients who developed diarrhoea while travelling abroad. Stool samples from all three patients contained CLB. Jejunal aspirates from two patients also yielded CLB. Conventional histology of jejunal biopsy specimens confirmed that two patients had enteritis. Electronmicroscopy of the same biopsy specimens revealed intraepithelial coccidia. These findings suggest that the small bowel is the site of infection of this new coccidian disease.

Adult↗
PubMed1993

Electron microscopy of rectal biopsies in HIV-positive individuals.

A series of 83 rectal biopsies was examined by electron microscopy (EM), 78 from HIV-seropositive patients (64 with diarrhoea, 9 with weight loss, and 5 asymptomatic) and 5 from controls without risk factors for HIV infection. Although EM identified the likely cause of the diarrhoea in only nine cases, the majority of symptomatic HIV-seropositive patients had abnormal biopsies including the presence of tubuloreticular structures, loss of microvilli, and oedema and disruption of autonomic nerves. Neuronal abnormalities were particularly common in patients with cryptosporidiosis, but no ultrastructural marker was specific to 'pathogen-negative' diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The chemotherapy of rodent malaria. L. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 3: Observations on 'Fenozan-50F', a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane.

A novel difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane ('Fenozan-50F') is a potent blood schizontocide against drug-sensitive and drug-resistant rodent malaria parasites. It also exerts some action against pre-erythrocytic schizogony, is a potent gametocytocide, and exerts a direct sporontocidal effect in infected mosquitoes. In the '4-day test' the ED90s are 6.8 and 6.0 mg/kg/day for four consecutive days by the subcutaneous and oral routes respectively against drug-sensitive Plasmodium berghei N, and 6.3 and 25 mg/kg against chloroquine-resistant P. yoelii NS in vivo. By the oral route against P. berghei N infection in mice, Fenozan-50F is about half as active as arteether but nearly three times as active as sodium artesunate. The activity of Fenozan-50F is retained against a wide spectrum of drug-resistant parasite lines, although those highly resistant to quinine or to artemisinin are less responsive at the ED90 level. At the ultrastructural level the compound, when administered to infected mice, causes marked changes in the membranes and ribosomes of trophozoites and young schizonts and of immature gametocytes, although few changes are apparent in mature gametocytes. Its toxicity appears to be very low when it is administered to mice by either the oral or subcutaneous route. Fenozan-50F is considered to be a good candidate for eventual use as a therapeutic agent for infection with polyresistant malaria in man.

Animals↗
PubMed1993

Electron microscopic changes in Enterocytozoon bieneusi following treatment with albendazole.

AIM: To identify and describe electron microscopic changes occurring in Enterocytozoon bieneusi in patients treated with albendazole. METHODS: Eighteen HIV seropositive patients with E bieneusi infection of the small intestine were treated with albendazole 400 mg twice a day for one month. Duodenal biopsy specimens obtained before and at the end of treatment were examined electron microscopically by a pathologist who was unaware of the clinical response. A semiquantitative assessment of the parasite load and description of the parasite morphology was made. RESULTS: A complete resolution of diarrhoea occurred in nine patients and a further three had a greater than 50% reduction in baseline stool frequency or volume. Three of the non-responders were also infected with cryptosporidium. There was a reduction in parasite load in those responding to treatment and an increase in abnormal forms in both responders and non-responders. CONCLUSION: The clinical response to albendazole treatment seen in some patients with small intestine microsporidiosis may be due to damage to the developmental stages, causing a partial inhibition of parasite reproduction.

Albendazole↗
PubMed1991

Use of electron microscopy in examination of faeces and rectal and jejunal biopsy specimens.

The stools and rectal biopsy specimens of 44 patients with AIDS and diarrhoea were examined by culture, light microscopy, and electron microscopy. In 13 patients examination of rectal biopsy material and faecal samples showed no pathogen, but in two of these, microsporidiosis was found by electron microscopical examination of jejunal biopsy specimens. This organism was also identified electron microscopically in one of the further five jejunal biopsy samples taken from patients with a known cause of diarrhoea. Blastocystis hominis infection was identified electron microscopically in six patients, all of whom had cryptosporidiosis additionally seen by light microscopy. Four of these six patients remained well for long periods, with only moderate diarrhoea, and follow up showed no evidence of blastocystis infection. In only four of 11 patients found to have cryptosporidium in their stools at light microscopy were organisms found at electron microscopy. Viral inclusions were only identified at electron microscopy in one of 10 patients with an opportunistic viral infection seen at light microscopy (cytomegalovirus n = 7, herpes simplex virus n = 3). No additional viral pathogens were detected in either stools or rectal biopsy material by electron microscopy. It is concluded that routine electron microscopic examination of stool samples or rectal biopsy material taken from patients with AIDS and diarrhoea is unnecessary and does not increase the yield of potential pathogens compared with standard microbiological techniques and histology.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Viral release from HIV-I-induced syncytia of CD4+ C8166 cells.

Infection of the permissive C8166 CD4+ lymphoid cell line with human immunodeficiency virus (HIV)-I rapidly leads to syncytium formation. Ultrastructural features of medium-sized (40 to 60 microns) syncytia and larger syncytia are presented, with emphasis upon HIV-I release from the syncytial surface and into intrasyncytial vacuoles. Although surface release of HIV-I is shown to diminish with increasing syncytial size, it does not totally stop. Massive HIV-I release and entrapment within intrasyncytial vacuoles is clearly apparent within the "foamy" multivacuolated zones within medium and large syncytia. Numerous multicored aberrant viruses are routinely detected within the intrasyncytial vacuoles, and double-budding events likewise are readily detectable at the vacuolar membranes, but less so at the syncytial surface. It is suggested that this observation may be a reflection of the more restricted availability of vacuolar membrane area for excessive viral budding as compared with that at the syncytial surface.

Cells, Cultured↗
PubMed1986

Fulminant hepatitis. An ultrastructural study.

Ultrastructural changes were observed in 23 consecutive patients who died from fulminant hepatic failure due to hepatitis B virus (4 cases), sporadic non-A, non-B (7), or paracetamol (acetaminophen) overdose (12) and in 3 patients with subacute hepatic necrosis of unknown cause. The findings are described in detail in 12 of these patients. Fatal fulminant hepatitis was characterised by massive confluent necrosis accompanied by collapse of reticulin framework and sudden drop-out of liver cells. No aetiological distinction could be made between different viral causes of fulminant hepatitis on the basis of ultrastructural pathology. Parenchymal changes in viral cases varied from reversible non-specific necrosis to irreversible changes where fragmentation of endoplasmic reticulum, mitochondria and nuclei had occurred. Differences in ultrastructural pathology between non-viral (paracetamol overdose-induced) and viral fulminant hepatitis were apparent. Modification of endoplasmic reticulum with enlarged attached polyribosomes, breakdown of plasma membrane, accumulation of cytoplasmic amorphous material and karyorrhexis and karyolysis of nuclei were the most prominent features in non-viral cases.

Acetaminophen↗
PubMed1985

Acute glandular fever-like illness in a patient with HTLV-III antibody.

A lymph node biopsy obtained from a patient with human T-cell lymphocytotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody, presenting with an acute glandular fever-like illness, was examined by electron microscopy. Numerous pathological changes were present in the biopsy, including hypertrophy of smooth endoplasmic reticulum, intracytoplasmic rod-like inclusions within the cisternae of endoplasmic reticulum, multivesicular bodies, test-tube and ring-shaped forms, and tubulo-reticular structures. Intranuclear and intracytoplasmic viral-like particles measuring 105-120 nm in diameter and small cytoplasmic particles measuring 50-70 nm in diameter were found in some degenerating lymph node cells. These pathological findings may reflect a host cell response to various pathological and viral stimuli resulting from immune deficiency owing to infection with HTLV-III/LAV.

Acute Disease↗