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M J Ryan

Publications and source records attributed to M J Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors.

Screening of a compound library for inhibitors of the fibroblast growth factor (FGFr) and platelet-derived growth factor (PDGFr) receptor tyrosine kinases led to the development of a novel series of ATP competitive pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. The initial lead, 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3- tert-butylurea (4b, PD-089828), was found to be a broadly active tyrosine kinase inhibitor. Compound 4b inhibited the PDGFr, FGFr, EGFr, and c-src tyrosine kinases with IC50 values of 1.11, 0.13, 0.45, and 0.22 microM, respectively. Subsequent SAR studies led to the synthesis of new analogs with improved potency, solubility, and bioavailability relative to the initial lead. For example, the introduction of a [4-(diethylamino)butyl]amino side chain into the 2-position of 4b afforded compound 6c with enhanced potency and bioavailability. Compound 6c inhibited PDGF-stimulated vascular smooth muscle cell proliferation with an IC50 of 0.3 microM. Furthermore, replacement of the 6-(2,6-dichlorophenyl) moiety of 4b with a 6-(3',5'-dimethoxyphenyl) functionality produced a highly selective FGFr tyrosine kinase inhibitor 4e. Compound 4e inhibited the FGFr tyrosine kinase with an IC50 of 0.060 microM, whereas IC50s for the inhibition of the PDGFr, FGFr, EGFr, c-src, and InsR tyrosine kinases for this compound (4e) were all greater than 50 microM.

Animals↗
PubMed1997

Gastroenteritis in children under 5 years of age in England and Wales.

Gastroenteritis is a major cause of illness in young children worldwide. The magnitude of this problem is underestimated, as many cases may not present for medical treatment and many that do present are not asked to provide a faecal specimen. In this study, laboratory reports of pathogens responsible for gastroenteritis in children under 5 years in England and Wales reported to the PHLS Communicable Disease Surveillance Centre from January 1990 to December 1994 were analysed. These reports were compared with food poisoning notifications and mortality attributable to gastroenteritis collated by the Office of Population Censuses and Surveys in the same age group over the same period. Thirty-nine per cent of the 167630 laboratory faecal identifications were of rotavirus. Reports were commonest in children under 1 year of age during the winter months. Salmonellas and campylobacters were isolated from 16% and 15% of the specimens reported respectively. During the study period salmonella reporting rates rose by 48% in this age group. Improving the microbiological quality of food and raising standards of food hygiene, together with increasing parental awareness of the possibility of food poisoning in young children, will help to reduce morbidity in this age group. The majority of childhood deaths attributable to gastroenteritis were associated with rotavirus infection. The introduction of recently developed vaccines against rotavirus could substantially reduce the level of morbidity in this age group.

Bacterial Infections↗
PubMed1997

Outbreaks of campylobacter infection: rare events for a common pathogen.

Campylobacter has been the commonest enteric pathogen isolated from humans in England and Wales since 1981, but few cases are linked to outbreaks. Twenty-one general outbreaks of campylobacter infection in England and Wales were reported to the PHLS Communicable Disease Surveillance Centre from 1992 to 1994. Seven hundred and six people were affected, nine cases were admitted to hospital, and no deaths were reported. The mean attack rate was 46.2% (SD 25.7%) and the mean duration of illness was 11 days (range 3 to 61 days). Outbreaks occurred throughout the year and throughout England and Wales. Infection in 18 outbreaks was reported to have been transmitted by food or water: eight were related to food (particularly poultry), six to contaminated water from a private water supply, and four to raw or inadequately pasteurised milk. General outbreaks of campylobacter infection appear to be unusual and should be investigated thoroughly. The new PHLS Campylobacter Reference Unit will assist in the identification of outbreaks of campylobacter infection and help to identify the risk factors associated.

Campylobacter Infections↗
PubMed1997

Outbreaks of infectious intestinal disease in residential institutions in England and Wales 1992-1994.

Data from the surveillance scheme of all general outbreaks of infectious intestinal disease in England and Wales reported to or otherwise identified, by the Public Health Laboratory Service Communicable Disease Surveillance Centre (CDSC) in 1992 and 1994 were used to describe the epidemiology of outbreaks of infectious intestinal disease in residential institutions. Outbreaks in residential institutions accounted for 22% (282/1275) of all outbreaks with most, 95% (268/282), occurring in homes for the elderly. The commonest pathogens in these 282 outbreaks were small round structured viruses 48% (132), salmonellas 17% (49). Clostridium perfringens 8% (23), rotavirus 5% (15) and Shigella sonnei 2% (6). The mode of transmission was described as mainly person to person in 71% (200 outbreaks) and mainly foodborne in 21% (58 outbreaks). The mean duration of outbreaks was 9 days. Duration of outbreaks varied with both the mode of transmission and the pathogen involved. The mean attack rate was 37%. Illness was reported in 5872 people. One or more individuals were admitted to hospital in 22% of outbreaks. Twenty-six deaths were reported, of which 18 were attributed to salmonellosis. Outbreaks in residential institutions are common. Attack rates are high and outbreaks are often prolonged, with high morbidity and mortality. There is a need for effective infection control policies which include appropriate training of staff, simple surveillance systems and readily available expert advice to ensure outbreaks are rapidly controlled.

Aged↗
PubMed1997

Bacterial joint infections in England and Wales: analysis of bacterial isolates over a four year period.

Data from 1158 cases of septic arthritis reported to the Public Health Laboratory Service (PHLS) Communicable Disease Control Centre (CDSC) from England and Wales over a 4 yr period (January 1990 December 1993) are presented. Reports where a bacterial organism was isolated from synovial fluid, or where an organism was isolated from blood cultures where a diagnosis of septic arthritis was reported, were examined. Reports of infection were more common in children (12.7% of infections were in the under 10 age group) and the elderly (54.7% aged 60 or over), and were higher in males in all age groups except in the elderly. The most common causative organisms remain staphylococcal and streptococcal species, comprising 40.6% (470) and 28% (324) of cases, respectively. The most common streptococci seen were Streptococcus pneumoniae and Lancefield group A beta-haemolytic Streptococcus organisms, 60.8% (197/324), although group B, C and G organisms accounted for 33.6% of streptococcal isolates (109/324). Haemophilus influenzae septic arthritis is not exclusive to children as 23.2% (16-69) of cases occurred over the age of 15. A total of 48% (635) of isolates were identified from both synovial fluid and blood cultures, 32.6% (378) from joint fluid alone and 12.5% (146) from blood cultures. Although this study excludes cases of septic arthritis where no organism was isolated, it presents important bacteriological information from a large number of isolates from England and Wales over a 4 yr period. Risk factors identified include a joint prosthesis, joint disease/connective tissue disorder. immunosuppression and diabetes.

Adolescent↗
PubMed1997

Localization of lipoprotein(a) in a monkey model of rapid neointimal growth.

Lipoprotein(a) [Lp(a)] has been proposed as a restenosis risk factor, but it is not known if Lp(a) is present in the injured arterial wall during the initial neointimal growth. The purpose of this study was to determine if Lp(a) is incorporated into the vessel wall during rapid neointimal formation after arterial injury in primates. In this model, distention of the iliac artery with an angioplasty catheter caused focal breaks in the internal elastic lamina (IEL) in 80% of the vessels and extensive IEL fragmentation with medial disruption in 20% of the vessels. Neointimal growth was noted in all injured arteries; thrombus formation was noted in 40% of the vessels. Based on morphometric measurements, injured arteries had neointimal areas of 0.41 +/- 0.05 (n = 4) and 0.83 +/- 0.23 (n = 6) mm2 at 14 and 28 days after injury, respectively. Control arteries had an intact IEL and a monolayer of intimal cells. Lp(a) localization was examined histologically by using a mouse monoclonal anti-Lp(a) antibody. Lp(a), found in all injured arteries, was localized primarily in the neointima in 50% of the vessels. In the subset of vessels with evidence of thrombus formation, intense Lp(a) immunostaining was associated with the thrombus. Lp(a) was specific to injured arteries as uninjured vessels did not stain. In addition, staining was not seen with a negative control, a nonspecific mouse IgG1 antibody. The presence of Lp(a) at the site of rapid neointimal growth supports a role for this lipoprotein in the response to vascular injury after balloon angioplasty.

Animals↗
PubMed1997

Consumer requests for information regarding psychotropic drugs: experience from a national medicines phone-in.

OBJECTIVE: To undertake a qualitative analysis of calls regarding psychotropic drugs that were received during a national medicines phone-in day. BACKGROUND: In July 1996, The Society of Hospital Pharmacists of Australia coordinated a national medications phone-in day, allowing consumers to seek information about medications from pharmacists and physicians using a toll-free telephone number. METHODS: Data collection forms were used to record the details of all calls answered during the phone-in day. Demographic data collected included the estimated age and gender of the caller. Other data collected included the drugs that were the subject of the inquiry and the category of questions. RESULTS: There were 42,096 attempted connections to the service, but because of limited telecommunications capacity, only 2245 callers were successfully connected. Psychotropic drugs were the primary subject of 367 calls, representing 16.4% of all inquiries for which data collection forms were completed. Antidepressants (56.1%) and benzodiazepines (24.8%) were the two most commonly encountered classes of psychotropic drugs. The greatest proportion of calls (57.2%) was related to adverse effects of medications. The nature of the inquiries regarding adverse drug effects was generally consistent with the adverse effects detailed in the scientific literature. CONCLUSIONS: The results of this 1-day, consumer-oriented drug information project suggest that there is a substantial need for this type of service. Patients treated with psychotropic medications should have access to unbiased, high-quality information about drug therapy.

Adult↗
PubMed1996

Risk factors for outbreaks of infectious intestinal disease linked to domestic catering.

The epidemiology of general outbreaks of infectious intestinal disease associated with domestic catering for large numbers is described and compared with foodborne outbreaks in other settings. From 1 January 1992 to 31 December 1994, the PHLS Communicable Disease Surveillance Centre identified 101 foodborne general outbreaks of infectious intestinal disease associated with domestic catering in England and Wales (16% of all foodborne outbreaks). Salmonella species were associated with 77 of the 101 outbreaks and S. enteriditis phage type 4 accounted for 57. Small round structured viruses were implicated in five outbreaks, Clostridium perfringens in four, Bacillus cereus in two, and Campylobacter sp and Escherichia coli in one each. No pathogen was identified in 11 outbreaks. Outbreaks occurred most commonly in summer. The commonest vehicles implicated were poultry/eggs in 44 outbreaks, desserts in 13, and meat/meat products in nine. Salad/vegetables, sauces, and fish/shellfish were each implicated in eight outbreaks. Raw shell eggs were implicated in a fifth of outbreaks. Inappropriate storage was the commonest fault, reported in association with 50 outbreaks (ambient temperature for long periods before serving in 29), inadequate heat treatment was reported in 35, cross contamination in 28, an infected food handler in 11, and other faults in 14. Outbreaks associated with catering on domestic premises were independently more likely than outbreaks in other settings to be associated with salmonellas, inappropriate storage of food, and consumption of poultry, eggs, or sauces. Public health services need to direct messages about the use, preparation, and storage of food to those who cater on domestic premises.

Disease Outbreaks↗
PubMed1996

Opportunist mycobacteria in England and Wales: 1982 to 1994.

Three thousand and fifty-two infections with opportunist mycobacteria were reported to the PHLS Communicable Disease Surveillance Centre from 1982 to 1994. The commonest reported species was Mycobacterium avium-intracellulare (MAI), followed by M. kansasii and M. malmoense. The annual totals of opportunist mycobacteria increased steadily over this period, mostly, but not exclusively, due to an increase in reports of MAI associated with HIV infection. There were also increases in reports of MAI not associated with HIV infection, and in reports of M. malmoense. The increase in reports of opportunist mycobacteria was seen throughout England and Wales, but underreporting of MAI infection in the National Health Service Thames regions appears to have increased in recent years. Continued referral of isolates of opportunist mycobacteria to one of the PHLS regional centres for mycobacteriology or the Mycobacterium Reference Unit, and reporting to CDSC, is essential for the surveillance of these infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

Epidemiological features of Coxiella burnetii infection in England and Wales: 1984 to 1994.

Q fever is an important zoonosis caused by the rickettsial organism Coxiella burnetii, which can result in life threatening illness, especially in those with an underlying cardiac defect. C. burnetii infections in England and Wales reported to the PHLS Communicable Disease Surveillance Centre between 1984 and 1994 were reviewed. A total of 1117 cases were reported, a third of which came from the South Western region. The annual totals fell over this period. The mean age of cases was 45 years, and 74% were men. Reports peaked in the month of May. Contact with animals, mainly cattle and sheep, was reported in 60 cases. Occupationally acquired infection was reported for 24 cases including abattoir workers, farmers, veterinary surgeons, hide handlers, and butchers. Forty-seven per cent of cases presented with respiratory symptoms, 7% with heart disease, and 5% with hepatitis. Seven per cent of cases reported travel abroad before becoming ill. Joint veterinary and medical investigations should be undertaken to establish the natural history of C. burnetii infection in England and Wales and formulate policies to prevent acute and chronic infections.

Adult↗
PubMed1996

Infectious intestinal disease in elderly people.

This paper analyses routinely available data on infectious intestinal diseases occurring in people aged 65 years and over in England and Wales from 1990 to 1994. These data include annual reports of consultations with general practitioners in spotter practices collated by the Royal College of General Practitioners, notifications of food poisoning collated by the Office of Population Censuses and Surveys, hospital admissions extracted from Hospital Episode Statistics data, reports of general outbreaks and laboratory reports of faecal isolates both collated by the PHLS Communicable Disease Surveillance Centre, and death registrations held at the Office of Population Censuses and Surveys. From 1 January 1990 to 31 December 1994 a total of 8,910 episodes of infectious intestinal disease in people aged 65 years and over were seen in the 93 spotter practices that care for a population of all ages of about 700,000. This extrapolates to about 925,000 cases in elderly people in England and Wales, if consultation rates in spotter practices are representative. Twenty-seven thousand two hundred and thirty-three cases of food poisoning were notified and 46,216 faecal isolates were reported in people of the same age group. The commonest pathogens detected were campylobacter, Clostridium difficile and salmonellas. Thirteen thousand five hundred and eighty-five people aged 65 years and over were admitted to hospital with infectious intestinal disease between 1 April 1991 and 31 March 1994. The PHLS Communicable Disease Surveillance Centre learnt of 360 outbreaks in residential institutions and hospital wards for elderly people between 1 January 1992 and 31 December 1994, 52% of which were caused by small round structured viruses. Seven hundred and seventy-seven deaths attributable to infectious intestinal disease in elderly people were registered from 1990 to 1994. Infectious intestinal disease is a largely preventable group of conditions that cause substantial morbidity and mortality in elderly people. Appropriate food hygiene and infection control measures, particularly in institutions, will help to reduce the incidence of infectious intestinal disease in elderly people.

Aged↗
PubMed1996

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

The therapeutic application of growth factors to human disease has become closer to reality with the advent of faster means of synthesizing these molecules and novel drug delivery strategies. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth. Purified extracts of EGF have been used clinically to modulate gastrointestinal secretion of hormones and accelerate healing. EGF is also reported to have both vascular smooth muscle contractile and relaxing activity Cardiovascular studies were performed with the bioactive 48-amino acid fragment of human EGF in rodents and primates to determine the effects of EGF on blood pressure and heart rate in conscious animals. Intravenous infusion of EGF induced an initial pressor response in rats followed by a prolonged decrease in blood pressure. In contrast, in monkeys, EGF had dose-related blood pressure-lowering effects only; significant hypotension was observed at doses ranging from 3 to 300 microg/kg i.v. Hypotension was associated with modest tachycardia in both species. To our knowledge, this is the first report of hemodynamic effects of EGF in primates, and it clearly documents that the mitogenic role of growth factors such as EGF is but one aspect of their physiology.

Animals↗
PubMed1996

The cost of inpatient care for acute infectious intestinal disease in England from 1991 to 1994.

Routine data from Hospital Episode Statistics and the Compendium of Health Statistics were used to estimate costs incurred by hospitals for inpatient treatment of infectious intestinal disease in England from 1991 to 1994. The estimated cost for the three years was 83,139,685 pounds associated with 108,037 inpatient episodes. The annualised age specific incidence of patients admitted to hospital for infectious intestinal disease varied from 25 to 613 per 100,000 population and was highest in children under 4 years of age. The cost of inpatient treatment attributable to infectious intestinal disease is high, but it represents only a proportion of the total costs of diarrhoeal illness. More detailed studies are needed to describe the total economic impact of infectious intestinal disease.

Acute Disease↗
PubMed1996

General outbreaks of infectious intestinal disease in England and Wales 1992 to 1994.

Data from the surveillance scheme of general outbreaks of infectious intestinal disease in England and Wales, reported to the PHLS Communicable Disease Surveillance Centre (CDSC), were used to review 1280 of the 1594 outbreaks identified between 1 January 1992 and 31 December 1994 for which a minimum data set was captured. The number of outbreaks reported in each regional health authority ranged from 31 in Mersey to 221 in Yorkshire. The commonest pathogens reported were salmonellas in 32% (412) of outbreaks, small round structured virus (SRSV) in 27% (342), Clostridium perfringens in 7% (90), and Shigella sonnei in 4% (46). The main mode of transmission was described as foodborne in 50% (642), over half of which were caused by salmonellas, and person to person in 39% (496), over half of which were caused by SRSV. Most outbreaks transmitted from person to person occurred in hospitals and in residential institutions for elderly people. Outbreaks lasted from one to 217 days (median five days) and their duration varied with the pathogen. The median attack rate was 37%. Illness was reported in 34,158 people, 751 of whom (2%) were admitted to hospital. There were 55 deaths, 28 of which were associated with salmonella and 12 with SRSV. Most of the outbreaks reported and the associated morbidity and mortality could have been prevented by following standard food hygiene practices, implementing infection control policies, and ensuring that food entering kitchens was of the highest microbiological quality possible.

Clostridium Infections↗
PubMed1996

Volumetric visualization of anatomy for treatment planning.

PURPOSE: Delineation of volumes of interest for three-dimensional (3D) treatment planning is usually performed by contouring on two-dimensional sections. We explore the usage of segmentation-free volumetric rendering of the three-dimensional image data set for tumor and normal tissue visualization. METHODS AND MATERIALS: Standard treatment planning computed tomography (CT) studies, with typically 5 to 10 mm slice thickness, and spiral CT studies with 3 mm slice thickness were used. The data were visualized using locally developed volume-rendering software. Similar to the method of Drebin et al., CT voxels are automatically assigned an opacity and other visual properties (e.g., color) based on a probabilistic classification into tissue types. Using volumetric compositing, a projection into the opacity-weighted volume is produced. Depth cueing, perspective, and gradient-based shading are incorporated to achieve realistic images. Unlike surface-rendered displays, no hand segmentation is required to produce detailed renditions of skin, muscle, or bony anatomy. By suitable manipulation of the opacity map, tissue classes can be made transparent, revealing muscle, vessels, or bone, for example. Manually supervised tissue masking allows irrelevant tissues overlying tumors or other structures of interest to be removed. RESULTS: Very high-quality renditions are produced in from 5 s to 1 min on midrange computer workstations. In the pelvis, an anteroposterior (AP) volume rendered view from a typical planning CT scan clearly shows the skin and bony anatomy. A muscle opacity map permits clear visualization of the superficial thigh muscles, femoral veins, and arteries. Lymph nodes are seen in the femoral triangle. When overlying muscle and bone are cut away, the prostate, seminal vessels, bladder, and rectum are seen in 3D perspective. Similar results are obtained for thorax and for head and neck scans. CONCLUSION: Volumetric visualization of anatomy is useful in treatment planning, because 3D views can be generated without the need for segmentation. When relationships among anatomical structures, rather than geometric models of them, are important, volume rendering presents advantages. The presented algorithm is readily adaptable to distributed parallel implementation on a network of heterogeneous workstations.

Anatomy, Cross-Sectional↗