A cohort study of duplex Doppler examinations of the carotid artery in primary open angle glaucoma

Objectives To explore the possibility of pathological change in the common carotid artery at the bifurcation and in the internal carotid artery beyond the bifurcation which could contribute to a reduced diastolic pressure as observed in primary open angle glaucoma. Design Duplex ultrasonic examinations of carotid bifurcations were conducted on 80 patients. Carotid artery defects were allocated into three types: no demonstrable flow defects, internal carotid artery abnormalities and disease in the carotid bulb. Setting Bristol Royal Infirmary Vascular Laboratory. Participants Eighty patients (mean age 69.6 years) providing a total of 160 sides to the analysis. Main outcome measures An estimated central retinal artery pressure, intraocular pressure and field loss were recorded for each side measured. Results Doppler investigations revealed significant levels of pathological change in the internal carotid distinct from changes at the carotid bulb. The disease revealed in the internal carotid artery was significantly associated with intraocular pressure (p = 0.032), with an effect small to medium in magnitude. The Q2 measure, derived from mean arterial pressure and intraocular pressure, was also substantively associated with disease in the internal carotid artery. Both intraocular pressure and the Q2 measure effectively discriminated between groups, with field loss providing rather less discriminating capability. There was a strong trend towards a higher intraocular pressures and a greater visual field loss with internal carotid artery disease. Conclusions Pathological changes in the extra cranial carotid artery in primary open angle glaucoma exceed those in the arteries classified as normal. The presence of disease specifically in the internal carotid artery emphasised the need for a mechanism for the evaluation of the internal carotid apart from the carotid bulb. A basis for clarifying the presence of an ischaemic zone is proposed

A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity.

The successful design and synthesis of a novel multifunctional platinum drug candidate with DNA binding, histone deacetylase inhibitory activity and enhanced selectivity for cancer cells are described

The effect of gold salts on tumour immunity and its stimulation by Corynebacterium Parvum.

The anti-inflammatory agent sodium aurothiomalate appears to act upon mononuclear phagocytes, inhibiting their lysosomal enzyme activity. Evidence is presented that gold salts can increase the number of lung tumour nodules that develop following intravenous injection of tumour cells and pretreatment can enhance the take of a subcutaneous tumour inoculum. In contrast, they do not affect the later growth of tumour. Gold salts can also suppress the action of systemically administered C. parvum in inhibiting the growth of subcutaneous tumours. These results are taken as supporting the evidence in favour of a fast acting nonspecific anti-tumour mechanism, probably macrophage mediated, that can be inhibited by gold salts and enhanced by C. parvum. The effect of gold salts upon other biological changes induced by C. parvum is examined, including its adjuvant action, and the results are discussed in the context of the mechanisms underlying the immunotherapeutic action of this organism

Sexually transmitted Q fever

We report the sexual transmission of Coxiella burnetii from a man with occupationally acquired Q fever to his wife. Fifteen days after coitus, his wife also developed serologically proven acute Q fever. C. burnetii DNA sequences were detected by polymerase chain reaction (PCR) performed on semen samples obtained from the husband at 4 and 15 months after the onset of acute Q fever, but PCR results were variable at 23 months, indicating the presence of few organisms.Adriana Milazzo, Robert Hall, Paul A. Storm, Ray J. Harris, William Winslow and Barrie P. Marmio

A novel dual-functioning ruthenium(II)–arene complex of an anti-microbial ciprofloxacin derivative — anti-proliferative and anti-microbial activity

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η6-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral ‘piano-stool’ geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics

Coxiella burnetii dormancy in a fatal tenyear multisystem dysfunctional illness: case report

In a previous study of a Q fever outbreak in Birmingham, our group identified a non-infective complex of Coxiella burnetii (C.b.) antigens able to survive in the host and provoked aberrant humoral and cell-mediated immunity responses. The study led to recognition of a possible pathogenic link between C.b. infection and subsequent long-term post Q fever fatigue syndrome (QFS). This report presents an unusually severe case of C.b. antigen and DNA detection in post-mortem specimens from a patient with QFS.We report a 19-year old female patient who became ill with an acute unexplained febrile encephalitis-like illness, followed by increasingly severe multisystem dysfunction and death 10 years later. During life, extensive clinical and laboratory investigations from different disciplinary stand points failed to deliver a definitive identification of a cause. Given the history of susceptibility to infection from birth, acute fever and the diagnosis of "post viral syndrome", tests for infective agents were done starting with C.b. and Legionella pneumophila. The patient had previously visited farms a number of times. Comprehensive neuropathological assessment at the time of autopsy had not revealed gross or microscopic abnormalities. The aim was to extend detailed studies with the post-mortem samples and identify possible factors driving severe disturbance of homeostasis and organ dysfunction exhibited by the course of the patient's ten-year illness. Immunohistochemistry for C.b. antigen and PCR for DNA were tested on paraffin embedded blocks of autopsy tissues from brain, spleen, liver, lymph nodes (LN), bone marrow (BM), heart and lung. Standard H&E staining of brain sections was unrevealing. Immuno-staining analysis for astrocyte cytoskeleton proteins using glial fibrillary acidic protein (GFAP) antibodies showed a reactive morphology. Coxiella antigens were demonstrated in GFAP immuno-positive grey and white matter astrocytes, spleen, liver, heart, BM and LN. PCR analysis (COM1/IS1111 genes) confirmed the presence of C.b. DNA in heart, lung, spleen, liver & LN, but not in brain or BM.The study revealed the persistence of C. b. cell components in various organs, including astrocytes of the brain, in a post-infection QFS. The possible mechanisms and molecular adaptations for this alternative C.b. life style are discussed.Olga A. Sukocheva, Jim Manavis, Tuck-Weng Kok, Mark Turra, Angelo Izzo, Peter Blumbergs and Barrie P. Marmio

Toxoplasma and coxiella infection and psychiatric morbidity: A retrospective cohort analysis

BACKGROUND: It has been suggested that infection with Toxoplasma gondii is associated with slow reaction and poor concentration, whilst infection with Coxiella burnetii may lead to persistent symptoms of fatigue. METHODS: 425 farmers completed the Revised Clinical Interview Schedule (CIS-R) by computer between March and July 1999 to assess psychiatric morbidity. Samples of venous blood had been previously collected and seroprevalence of T. gondii and C. burnetii was assessed. RESULTS: 45% of the cohort were seropositive for T. gondii and 31% were positive for C. burnetii. Infection with either agent was not associated with symptoms reflecting clinically relevant levels of concentration difficulties, fatigue, depression, depressive ideas or overall psychiatric morbidity. CONCLUSIONS: We do not provide any evidence that infection with Toxoplasma gondii or Coxiella burnetii is associated with neuropsychiatric morbidity, in particular with symptoms of poor concentration or fatigue. However, this is a relatively healthy cohort with few individuals reporting neuropsychiatric morbidity and therefore the statistical power to test the study hypotheses is limited

Haiku - a Scala combinator toolkit for semi-automated composition of metaheuristics

There is an emerging trend towards the automated design of metaheuristics at the software component level. In principle, metaheuristics have a relatively clean decomposition, where well-known frameworks such as ILS and EA are parametrised by variant components for acceptance, perturbation etc. Automated generation of these frameworks is not so simple in practice, since the coupling between components may be implementation specific. Compositionality is the ability to freely express a space of designs ‘bottom up’ in terms of elementary components: previous work in this area has used combinators, a modular and functional approach to componentisation arising from foundational Computer Science. In this article, we describeHaiku, a combinator tool-kit written in the Scala language, which builds upon previous work to further automate the process by automatically composing the external dependencies of components. We provide examples of use and give a case study in which a programatically-generated heuristic is applied to the Travelling Salesman Problem within an Evolutionary Strategies framework