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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 19 recordsLinked to original sources

Two separate outbreaks of Salmonella enteritidis phage type 14b food poisoning linked to the consumption of the same type of frozen food.

OBJECTIVES: To ascertain, using a combination of epidemiological, environmental and microbiological methods of investigation, a possible link between two outbreaks of salmonella food poisoning. METHODS: Case-control studies were carried out on the known at-risk populations. Environmental investigations took place in the food preparation areas used for the social functions and microbiological examinations were carried out on faecal specimens obtained from cases, environmental swabs, and food specimens when these were available. RESULTS: In both outbreaks, illness was associated with the consumption of sesame prawn toast (outbreak one P<0.004; outbreak two P<0.0001). Salmonella enteritidis phage type 14b was cultured from the faecal specimens of cases in both outbreaks and from a packet of sesame prawn toast used for the second outbreak function. Molecular typing methods indicated that the salmonella cultures obtained in both outbreaks were indistinguishable from each other and from cultures obtained from imported Spanish eggs in a previous survey. Imported Spanish eggs were used in the manufacture of the sesame prawn toast. CONCLUSIONS: Adequate cooking must take place of raw food products, which should be clearly labelled as such. Manufacturers should consider, when possible, the use of pasteurized egg in the preparation of food products.

Adult↗

Interactions of malnutrition and immune impairment, with specific reference to immunity against parasites.

1. Clinical malnutrition is a heterogenous group of disorders including macronutrient deficiencies leading to body cell mass depletion and micronutrient deficiencies, and these often coexist with infectious and inflammatory processes and environmental problems. 2. There is good evidence that specific micronutrients influence immunity, particularly zinc and vitamin A. Iron may have both beneficial and deleterious effects depending on circumstances. 3. There is surprisingly slender good evidence that immunity to parasites is dependent on macronutrient intake or body composition.

Animals↗

Not all microscopes are equal.

A functional microscope is the most important and most expensive piece of equipment required for smear microscopy. Global Fund monies have provided a unique opportunity to equip laboratories in low-resource countries, but these funds must be spent wisely. Cheap microscopes are superficially appealing. However, higher-quality microscopes generally have better optics and last longer. International agencies should consider establishing a purchasing service to assist countries in their microscope procurement. Such a system would provide quality assurance and increased purchasing power.

Humans↗

Nitazoxanide for persistent diarrhoea in Zambian acquired immune deficiency syndrome patients: a randomized-controlled trial.

BACKGROUND: Adults with acquired immune deficiency syndrome and persistent diarrhoea in Zambia have intestinal infection, predominantly protozoa. AIM: To search for treatment which can be offered with minimal investigation, we carried out a double-blind, randomized-controlled trial of nitazoxanide (a drug with a range of activity against parasites and bacteria). METHODS: Patients with diarrhoea of 1 month duration or longer were randomized to receive nitazoxanide (1000 mg twice daily) or placebo for 2 weeks. End-points were clinical response, parasitological clearance and mortality. RESULTS: Two hundred and seven adults were randomized; 42 died during the study. The primary assessment of efficacy was made after 17 days. Clinical response was observed in 56 (75%) of 75 patients receiving nitazoxanide and 45 (58%) of 77 patients receiving placebo (P = 0.03). The rate of improvement was markedly higher in patients with CD4 counts under 50 cells/microL receiving nitazoxanide (P = 0.007). The benefit was largely restricted to the period when the drug was being administered. No difference was seen in parasitological clearance between the two groups. Mortality was 19% by 4 weeks of follow-up and did not differ with treatment allocation. CONCLUSIONS: Nitazoxanide given orally for 14 days was associated with clinical improvement in Zambian acquired immune deficiency syndrome patients with diarrhoea, especially those with very low CD4 counts.

Acquired Immunodeficiency Syndrome↗

Anxiety and depression in the acute porphyrias.

A previous study of self-rated psychosocial aspects in patients with acute porphyria found that depression, and particularly anxiety, is more common in porphyria patients than in the general population or general medical outpatient attenders. Nearly half of the sample (46%) reported at least some problem with anxiety and/or depression: anxiety caseness was 26% and depression caseness was 13%. This paper extends our previous observations and investigates further the associations between porphyria and anxiety, depression and general mental health in 90 patients (58 acute intermittent porphyria, 32 variegate porphyria). The findings of this study confirm that anxiety is raised in patients with acute intermittent porphyria and with variegate porphyria, in both males and females, compared to the normative population and, using a series of questionnaires exploring the physical and psychosocial features of anxiety, that this anxiety is experienced as a 'relatively stable personality trait', rather than a 'transitory emotional state' (i.e. intrinsic rather than secondary to the porphyria).

Anxiety↗

Coronary disease in the puerperium.

The manifestation of an acute coronary syndrome in women in the postpartum period is a rare but important clinical scenario, which, because of its multiple possible aetiologies, requires a different approach to management on the part of the clinician. Spontaneous coronary artery dissection (SCAD) is the most likely cause of an acute coronary syndrome in women in the puerperium. Unfortunately there is no medical consensus on the correct management pathway of such patients, but there is evidence that these patients have an improved prognosis when referred for bypass surgery or percutaneous intervention.

Journal Article↗

Probiotics: an emerging therapy.

There is considerable clinical interest in the utility of probiotic therapy--the feeding of (live) non-pathogenic bacteria, originally derived from the alimentary tract, for disease treatment or health promotion. The microflora of the gastrointestinal tract is essential for mucosal protection, for immune education and for metabolism of fecal residue. Physiological disturbances of these processes, when they occur, result from: i) alteration of a microbial ecosystem, originally conserved by evolution; ii) reduced consumption of microorganisms; iii) invasion of pathogens; or iv) modern interventions. Recent data support the use of proven probiotic organisms in prevention and treatment of flora-related gastrointestinal disorders including inflammatory bowel disease, infectious and antibiotic related diarrheas, and post-resection disorders including pouchitis. Therapeutic activity of probiotic bacteria can be due to competition with pathogens for nutrients and mucosal adherence, production of antimicrobial substances, and modulation of mucosal immune functions. Although a promising treatment, controlled clinical trials are necessary to validate the benefit of probiotics.

Animals↗

Antibiotic resistant tuberculosis and bovine tuberculosis in an Irish hospital population (1991 to 2001).

Of 864 consecutive culture positive cases of tuberculosis (TB) treated in the period 1991-2001, a total of 19 (2.1%) were M. bovis and 32 (3.7%) were drug resistant - Multi-Drug Resistant Tuberculosis (MDR-TB) (8); poly drug resistant (7); mono drug resistant (17). Iatrogenic factors were important in the cause of resistance in 9 cases (4 cases of MDR-TB): in 6 cases patients factors were important. Comparison with previous report for the period 1982-1985 showed relatively more isolates of M. bovis (p = 0.02); drug resistant TB (p = 0.005); and MDR-TB (p = 0.01) in the current study. Comparison with the background population of TB patients showed that patients with resistant TB were more likely to have a previous history of TB (Relative Risk = 3.58) and more likely to be foreign nationals (Relative Risk = 1.93) We conclude that while overall incidence of TB has declined that in relative terms the caseload of drug resistant TB and MDR-TB has increased. The drug cost of treating MDR-TB may be as high as 44,900 euros per patient.

Adolescent↗

Interaction of artificial metallic objects with biosusceptometric measurements.

In human subjects, metallic objects cause distortions of the magnetic fields used by magnetic resonance imaging (0.5 - 3.0 T) or by SQUID biomagnetic liver susceptometry (0.1 - 30 mT) and may lead to artifacts in the measurement of the relaxation rate or the magnetic susceptibility. In biosusceptometry, the measured signal will depend not only on the magnetic susceptibility of the object, but also on its distance to the sensor assembly, and in case of ferromagnetic objects, on the direction of its remanent field. The magnetic susceptibility of a vascular access port-a-cath and of surgical clips have been measured by a SQUID biosusceptometer. Additionally, the impact from port-a-caths and dental braces on liver iron concentration (LIC) measurements was measured in vivo with respect to their radial distance from the gradiometer center axis. For the port-a-cath, a mean magnetic volume susceptibility of (83.5 +/- 0.3).10(-6) SI-units was found, which may be compared with the magnetic susceptibility of titanium at room temperature of (180 +/- 2).10(-6) SI demonstrating the absence of ferromagnetic contamination. At a radial distance of 5 cm from the gradiometer center axis, the voltage amplitude is similar to the signal generated by a normal liver. Modern surgical clips have nearly no impact on LIC measurements. However, dental braces although further away from the center axis, often superimpose the signal even from an iron overloaded liver. Depending on the Ni-content, these objects reveal ferromagnetic properties and contribute in first order with a one parameter reciprocal distance function to the measured liver iron signal.

Artifacts↗

The effects of a 12-week group exercise programme on physiological and psychological variables and function in overweight women.

OBJECTIVES: The aim of this study was to investigate the effect of a 12-week functional exercise programme on overweight women. METHODS: Twenty-six subjects (n=13 exercisers, n=13 controls) aged (mean+/-SD) 63 (+/-4) years completed the study. The exercise sessions were carried out twice each week for 12 weeks. The variables measured were body mass, body mass index, skin-fold thickness, resting blood pressure, total blood cholesterol, chair rise, timed 'up and go' test, 20-m walk,lifting a 1- and a 2-kg bag on to a shelf, stair walking, 'sit and reach' flexibility test, Life Satisfaction Index and Physical Self-perception Profile for Older Adults. The exercise sessions consisted of 40-min sessions during which the subjects performed aerobic and strength exercises. RESULTS: Paired analyses showed that body mass, body mass index, blood pressure (systolic and diastolic values), 'up and go' time, time to complete a 20-m walk, time to lift a 1- and a 2-kg bag with both the right and left arms onto a shelf, and stair climbing-total time and ascent time-decreased significantly in the exercise group. Also, the exercise group improved their Life Satisfaction Index score significantly compared with the control group. CONCLUSIONS: The results indicate that a functional exercise programme has the potential to improve performance in a number of physiological variables and functional activities in overweight women. The exercise programme enhanced life satisfaction.

Aged↗

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.

Aged↗

Stem cell clonality and genotoxicity in hematopoietic cells: gene activation side effects should be avoidable.

Two serious adverse events involving activation of the LMO2 oncogene through retrovirus vector insertion in the otherwise extremely successful first gene therapy trial for X-linked severe combined immunodeficieny type 1 (SCID-X1) had initially caused widespread concern in the patient and research communities. Careful consideration 1 year after diagnosis of the second case still finds 12 of the treated patients clearly benefiting from gene therapy (freedom from treatment failure, 80%; survival 100%), a situation that should not portend the end of gene therapy for this disease, and is, in fact encouraging. While current approaches are justified to treat patients with otherwise life-threatening disorders, a broad consensus has developed that systematic basic research is required to further understand the pathophysiology of these serious adverse events and to provide new insights, enabling safer and more effective gene therapy strategies. With the continued success of SCID-X1 gene therapy in the majority of patients treated, it is of even greater importance to understand exactly which vector element or combination of elements predispose to toxicity. An in-depth study of the mechanisms behind the activation of the LMO2 and gammac genes will be highly instructive for the development of safer procedures and vectors. We summarize the central observations, ongoing experimental approaches, new concepts, and developments relevant to understanding, interpreting, and eventually overcoming the real and perceived obstacles posed by insertional mutagenesis due to gene transfer vectors.

Adaptor Proteins, Signal Transducing↗

Paneth cell granule depletion in the human small intestine under infective and nutritional stress.

Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins. Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status. We examined human tissue to determine whether Paneth cell numbers, distribution or granule morphology are altered in infective, inflammatory and nutritional disorders. Archival sections from infective disorders (giardiasis, cryptosporidiosis, HIV, helminth infection) were compared with active inflammatory conditions (coeliac, Crohn's and graft-versus-host diseases) and histologically normal tissues. A subset of tissues was studied by electron microscopy and TUNEL staining for apoptosis. Human defensin-5 (HD5) peptide and mRNA was analysed by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction. Sections from a tropical population cohort study were then analysed to determine the relationship of granule depletion to infection, nutritional status and plasma zinc concentration. In HIV-related cryptosporidiosis, but not other disorders, Paneth cells were reduced in number and markedly depleted of granules. Paneth cell granule depletion was associated with reduced HD5 immunoreactivity, but this was not due to apoptosis and there was no reduction in mRNA transcripts. In the tropical population studied, depletion of granules was associated with reduced body mass index, reduced plasma zinc levels and HIV infection. Paneth cell granules in human small intestine may be depleted in response to infective and nutritional stress. We postulate that this is one mechanism through which zinc status influences host susceptibility to intestinal infection.

AIDS-Related Opportunistic Infections↗

Topical benzydamine cream and the relief of pressure pain.

OBJECTIVE: To determine whether topical benzydamine hydrochloride 3% cream is more effective than placebo in reducing pain related to pressure areas in palliative care patients. DESIGN: Randomized double-blind, placebo-controlled trial. SETTING: Three specialist palliative care units in the north of England, with local ethical committee approval for all sites. SUBJECTS: Hospice in-patients with pain related to pressure areas. INTERVENTIONS: A single application of either benzydamine hydrochloride 3% cream or placebo cream to the painful pressure area. MAIN OUTCOME MEASURES: Pain assessed using 100 mm VAS, an 11-point numerical pain score and a five-point pain relief score. RESULTS: There was no statistically significant difference between topical benzydamine hydrochloride 3% cream and placebo cream in reducing pain related to pressure areas in palliative care patients. CONCLUSIONS: This study does not demonstrate a statistically significant difference between the two treatments. However the study does provide reliable information with respect to the use of different pain measurement tools in late-stage palliative patients. It also provides information regarding the baseline characteristics of this group of patients which may be useful in the planning of any future similar studies.

Administration, Cutaneous↗

The changing face of tuberculosis control in a rural district of New Zealand.

SETTING: Waikato Health District (WHD), New Zealand. OBJECTIVE: To describe the changing epidemiology of TB in the WHD and the factors responsible for this. DESIGN: Descriptive epidemiological study of all notified TB cases from the WHD from 1 January 1992 to 31 December 2001. Major outcome measures were delay of diagnosis and treatment outcome. RESULTS: There were 244 cases included. Over the 10-year period, TB incidence has remained stable in the WHD. There has been a significant reduction of TB in the Maori population (from 30.3 to 12.5/100,000, P = 0.03). This has been matched by a rise in the overseas-born population (from 4.6 to 21.2/100,000, P = 0.04). Tuberculosis became a predominantly urban disease during the study period. Delay in diagnosis (>4 weeks) occurred in 85% of cases, with significantly more delays in older age groups. Use of directly observed therapy (OR 3.65, 95%CI 1.24-10.76), and being a migrant (OR 3.52, 95%CI 1.74-7.09), were significantly associated with improved treatment outcome. CONCLUSION: A significant change in the epidemiology of TB has occurred over the last decade. Tuberculosis control strategies need to be developed to effectively diagnose and treat patients from diverse cultural backgrounds.

Adult↗

The role of Cryptosporidium parvum-derived phospholipase in intestinal epithelial cell invasion.

In the Cryptosporidium parvum-infected intestinal epithelial cell, the parasite occupies an unusual extracytoplasmic location at the luminal surface, but how the invading zoites interact with the host cell to achieve this niche is poorly understood. This study examined the role of secretory phospholipase A(2) (sPLA(2)), a known virulence factor for several pathogenic microorganisms, in establishing C. parvum intracellularly. Initially, it was established that there was sPLA(2) activity in homogenates of C. parvum oocysts. C. parvum reproduction in two human enterocyte cell lines was significantly reduced by a specific PLA inhibitor, p-bromophenacylbromide, and by sheep anti-sPLA(2) antibodies developed against PLA(2) of bee ( Apis mellifera) venom. Treatment of either C. parvum sporozoites or enterocytes with sPLA(2) derived from cobra ( Naja naja) venom before initiation of infection increased the numbers of intracellular parasites. Thus, C. parvum PLA(2 )may play an important part in establishing the parasite within the enterocyte.

Acetophenones↗

The anatomical distribution of cerebral gliomas in mobile phone users.

We analysed the association between mobile phone use and the anatomical distribution of glial brain tumours in Irish neurosurgical patients. All patients with unilateral histologically proven glioma were enrolled over a 12 month period. We hypothesised that were a cellular phone to cause a glioma then it would do so on the dominant hand side. Fifty mobile phone users and twenty three non-users were identified. The vast majority of patients (69/73) were right handed and the right side of the brain was more common as the tumour site (48/73). Fisher's exact test revealed no statistical significance for glioma location based on the handedness of the patient in the mobile phone user group and location of the tumour in both user and non-user groups. We discuss our findings and the stable trend in the incidence of reported glioma cases.

Adult↗

Albendazole chemotherapy for AIDS-related diarrhoea in Zambia--clinical, parasitological and mucosal responses.

BACKGROUND: Albendazole reduces diarrhoea in African AIDS patients, but it is unclear if the clinical response to treatment reflects pathogen eradication and/or mucosal recovery. METHODS: Adults with HIV-related persistent diarrhoea were treated with albendazole 800 mg twice daily for 14 days. Clearance of parasites was evaluated at 3 and 6 weeks by stool microscopy. At baseline and at 6 weeks duodenal biopsies were taken for electron microscopy (EM) and morphometry. RESULTS: Ten (7%) of 153 patients had cryptosporidiosis, 54 (37%) had isosporiasis and 23 (16%) had microsporidiosis. By 3 weeks, these protozoa were cleared in 27 (46%) of 59 patients initially positive. By 6 weeks, 34 (39%) of 87 patients experienced complete clinical response, 18 (21%) partial response and 35 (40%) no response. Crypt depth increased by 15% over 6 weeks (P < 0.001), but villous height increased only in patients with complete response (median + 50 microm, interquartile range (IQR) 2-90, compared to patients with partial (+ 4 microm, IQR -15,41) or no response (-13 microm, IQR -2,12; P=0.008)). Fifteen patients died: body mass index < 17.5 kg/m(2) and crypt depth < 180 microm independently predicted death. CONCLUSIONS: Albendazole therapy reduced the burden of protozoal infection and promoted mucosal recovery in patients with a complete clinical response.

Adult↗