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Biomedical subjects

P Ryan

Publications and source records attributed to P Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1999

The relationship between birth weight and blood pressure amplifies from childhood to adulthood.

OBJECTIVE: To investigate relationships between birth characteristics and blood pressure at age 20 years and to assess whether effects of birth weight on blood pressure are amplified from childhood to adulthood. DESIGN: A longitudinal study of 584 men and women from Adelaide, Australia, examined previously at 8 years and followed up at age 20 years. RESULTS: Birth weight was negatively associated with systolic pressure at age 20 years in men (regression coefficient 2.6 mmHg per kg; 95% confidence interval 0.7, 4.4) and women (regression coefficient 4.6 mmHg per kg; 95% confidence interval 2.9, 6.4), after adjustment for current weight There was an interaction with current size (P = 0.05 for men and P = 0.09 for women), such that effects were enhanced among individuals with relatively high weight or weight for height. Shortness at birth, thinness at birth, and low birth weight relative to placental weight were also associated with elevated systolic pressure at age 20 years. Effects of birth weight on blood pressure were stronger at age 20 than at age 8 years (P < 0.01 for men and P = 0.03 for women). This was not due simply to increased variability of blood pressure in adulthood. There were greater rises in blood pressure with age among individuals of relatively low birth weight. CONCLUSIONS: These findings are further evidence that poor fetal growth is associated with elevated blood pressure in later life. The results support the hypothesis that the relationship is amplified with increasing age.

Adolescent↗
PubMed1999

Meat, metabolic genotypes and risk for colorectal cancer.

Persuasive data exist as to the importance of environmental factors in the pathogenesis of sporadic colorectal cancer. One possibility is that the effect of environmental factors varies between individuals, perhaps on the basis of inherited variation (polymorphism) in genes which influence the activation or inactivation of dietary carcinogens. Thus far, the focus has been on acetylator genes (NAT1, NAT2) and the activation of heterocyclic amines, carcinogens generated by cooking meat for prolonged periods at high temperature. Three case-control studies and one prospective study have shown a consistent trend towards higher risks for cancer with higher intakes of meat in rapid acetylators for NAT1, NAT2 or both genotypes. Other links between meat, cooking methods, metabolic genotypes and risk for cancer might include enhanced activation of polycyclic aromatic hydrocarbons and N-nitroso compounds by variant genotypes of CYP1A1 and CYP2E1, respectively, and modulation by meat of the protective effect of the E4 allele of apolipoprotein E on risk for cancer of the proximal colon.

Acetylation↗
PubMed1998

Biosafety monitoring of patients receiving intracerebral injections of murine retroviral vector producer cells.

Patients with recurrent malignant brain cancer, who were receiving gene therapy by intracerebral injection of murine retroviral vector producer cells (VPCs), were monitored for the presence of replication-competent retrovirus (RCR). RCR sequences were not detected by polymerase chain reaction (PCR) in any of the 608 peripheral blood leukocyte (PBL) samples analyzed. Vector DNA sequences were detected transiently in PBL samples from a subset of 34 patients. Humoral immune responses to a retroviral core protein p30 and murine VPC were detected in some patients, most frequently in patients receiving repeated administrations of VPC. RCR was not detected in biological assays of PBLs from 41 patients who had either anti-retroviral antibodies in sera and/or vector DNA in PBLs. Our data suggest that in situ generation of RCR was not detected following intracerebral inoculation of VPCs in any of the 128 patients evaluated.

Animals↗
PubMed1998

Interaction between pseudorabies virus and heparin/heparan sulfate. Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain.

Cell surface heparan sulfate serves as an initial receptor for a number of herpesviruses including pseudorabies virus (PrV). It has been demonstrated that the heparan sulfate-binding domain of PrV glycoprotein C is composed of three discrete clusters of basic residues corresponding to amino acids 76-RRKPPR-81, 96-HGRKR-100, and 133-RFYRRGRFR-141, respectively, and that these clusters are functionally redundant, i.e. each of them could independently support PrV attachment to cells (Flynn, S. J., and Ryan, P. (1996) J. Virol. 70, 1355-1364). To evaluate the functional significance of each of these clusters we have used PrV mutants in which, owing to specific alterations in glycoprotein C, the heparan sulfate-binding site is dominated by a single specific cluster. These mutants exhibited different patterns of susceptibility to selectively N-, 2-O-, and 6-O-desulfated heparin preparations in virus attachment/infectivity assay. Moreover PrV mutants differed as regard to efficiency of their attachment to and infection of cells pretreated with relatively low amounts of heparan sulfate-degrading enzymes. Furthermore glycoprotein C species, purified from respective mutants, bound heparin oligosaccharide fragments of different minimum size. These differences suggest that specific clusters of basic amino acids of the heparan sulfate-binding domain of glycoprotein C may support PrV binding to different structural features/stretches within the heparan sulfate chain.

Amino Acid Sequence↗
PubMed1998

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

Adult↗
PubMed1998

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.

Adult↗
PubMed1998

An international case-control study of adult glioma and meningioma: the role of head trauma.

BACKGROUND: Increased brain tumour risk after head trauma suggested by case reports and clinical series has been previously studied epidemiologically with mixed results. An international multicentre case-control study investigated the role of head trauma from injury or sports participation in adult brain tumour risk. METHODS: In all, 1178 glioma and 330 meningioma cases were individually or frequency matched to 2236 controls. Only exposures that occurred at least 5 years before diagnosis and head injuries that received medical attention were considered. RESULTS: Risk for ever having experienced a head injury was highest for male meningiomas (odds ratio [OR] = 1.5, 95% confidence interval [CI] : 0.9-2.6) but was lower for 'serious' injuries, i.e. those causing loss of consciousness, loss of memory or hospitalization (OR = 1.2, 95% CI: 0.6-2.3). Among male meningiomas, latency of 15 to 24 years significantly increased risk (OR = 5.4, 95% CI: 1.7-16.6), and risk was elevated among those who participated in sports most correlated with head injury (OR = 1.9, 95% CI: 0.7-5.3). Odds ratios were lower for male gliomas (OR = 1.2, 95% CI : 0.9-1.5 for any injury; OR = 1.1, 95% CI: 0.7-1.6 for serious injuries) and in females in general. CONCLUSIONS: Evidence for elevated brain tumour risk after head trauma was strongest for meningiomas in men. Findings related to sports should be interpreted cautiously due to cultural variability in our data and our lack of complete data on physical exercise in general which appeared to be protective.

Adult↗
PubMed1998

Carbon monoxide exposures in Australian workplaces could precipitate myocardial ischaemia in smoking workers with coronary artery disease.

BACKGROUND: Quite low levels of carbon monoxide (CO) exposure have been shown experimentally to induce myocardial ischaemia in subjects with coronary artery disease. This study examines the actual exposure levels in Australian workplaces under normal operating conditions, to assess whether the resulting carboxyhaemoglobin (COHb) levels are high enough to present a risk of myocardial ischaemia in any workers who may have recognised or unrecognised coronary artery disease. METHODS: A total of 84 workers took part in the study, 60 of whom were working in an environment where a combustion process was taking place indoors and were therefore classified as exposed to CO. Ambient CO levels and end-expiratory CO levels (the latter as a predictor of COHb) were measured two-hourly and the number of cigarettes smoked over an eight-hour shift recorded. RESULTS: Mean workplace CO levels throughout the shift ranged between three and 12 ppm. Mean COHb ranged between 0.7% and 2.1% in non-smokers and 2.1%-7.6% in smokers, except for a single reading of 12.5% in forklift operations (one smoker). Exposed workers had significantly higher COHb levels than the non-exposed, both for smokers and non-smokers. Smoking also had an important independent effect on COHb. CONCLUSION: Under workplace conditions prevailing in industries where combustion processes are occurring indoors, CO exposures are unlikely to be high enough to cause myocardial ischaemia in non-smokers. However in a worker whose COHb is already raised from smoking, an increment from such occupational environments could be sufficient to induce myocardial ischaemia in workers with coronary artery disease.

Australia↗
PubMed1998

The impact of depression on the physical health of family members.

BACKGROUND: Depressive illness is common. Depression in one family member is associated with an increased incidence of psychopathology in other family members. There are no data on the physical well being of the families of depressed individuals. AIM: To compare physical morbidity of family members of depressed patients with that of family members of comparison patients. METHOD: A comparative follow-up study from case notes. Two hundred and one subjects from 88 families with an index family member diagnosed with depression ('depression families') were compared with 200 subjects from 88 families with a matched index subject without depression ('comparison families'), using the Duke University Illness Severity Scores (ISS) to assess burden of illness experienced by both groups. RESULTS: The cumulative incidence of depression over 11 months in depression families was 8.9% compared to 1.4% in the Family Practice Unit as a whole. Members of depression families had significantly greater ISS than members of comparison families (difference in means = 0.164; 95% confidence interval (CI) 0.113-0.215; P < 0.001). Excluding family members with depression (in addition to the index subject), ISS of members of depression families remained significantly greater than the comparison group (difference in means = 0.136; 95% CI 0.083-0.189; P < 0.001). Among depression families, mean ISS was significantly higher after presentation of depression in index subjects compared with before (difference in means = 0.155; 95% CI 0.115-0.194; P < 0.0001). No significant difference was seen between ISS of depression and comparison families before presentation of depression (difference in means = 0.008; 95% CI -0.004-0.058; P = 0.74). CONCLUSION: Depression in patients is associated with increased physical morbidity in their families.

Adult↗
PubMed1997

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy.

Radiation resistant squamous cell carcinoma of the head and neck cell line JSQ-3 carries a mutant form of tumor suppressor gene p53. Treatment of these cells with an adenoviral vector containing wild-type p53 (Av1p53) was able to inhibit their growth in vitro and in vivo while having no effect on normal cells. More significantly, introduction of wtp53 also reduced the radiation-resistance level of this cell line in vitro, in a viral dose-dependent manner. Furthermore, this radiosensitization also carried over to the in vivo situation where the response of JSQ-3 cell-induced mouse xenografts to radiotherapy was markedly enhanced after treatment with Av1p53. Complete, long-term regression of the tumors for up to 162 days was observed when a single dose of Av1p53 was administered in combination with ionizing radiation, demonstrating the effectiveness of this combination of gene therapy and conventional radiotherapy. This sensitization of tumors to radiation therapy by replacement of wtp53 could significantly decrease the rate of recurrence after radiation treatment. Since radiation is one of the most prevalent forms of adjunctive therapy for a variety of cancers, these results have great relevance in moving toward an improved cancer therapy.

Adenoviridae↗
PubMed1997

Restoration of the G1 checkpoint and the apoptotic pathway mediated by wild-type p53 sensitizes squamous cell carcinoma of the head and neck to radiotherapy.

BACKGROUND: A significant number of squamous cell carcinomas of the head and neck (SCCHN) resist radiation treatment, the most common form of adjuvant therapy for this disease. The presence of a mutant form of the tumor suppressor gene p53 has been correlated with disruption of programmed cell death (apoptosis) and reduced cell cycle arrest, resulting in increased radiation resistance and survival. METHODS AND RESULTS: We introduced by means of an adenoviral vector a functional p53 gene into a radiation-resistant SCCHN cell line that harbors mutant p53. Replacement of wild-type p53 restored the G1 block and apoptosis in these cells in vitro. Moreover, introduction of wild-type p53 sensitized SCCHN-induced mouse xenografts to radiotherapy in vivo. CONCLUSION: The combination of p53 replacement gene therapy with conventional radiotherapy may treat SCCHN more effectively.

Animals↗
PubMed1997

Registration bone scan in the evaluation of wrist pain.

We assessed the value of bone scintigraphy combined with X-ray registration for the diagnosis and management of wrist pain in 65 patients. Studies were reported independently by two observers before and after registration. Registration improved localization of scan abnormalities in 53% (observer 1) and 61% (observer 2). In these patients, the bone scan contributed to the diagnosis independently of the X-ray in 37% and the management was altered in 31%. The value of the bone scan in the early diagnosis and management of wrist pain is increased when it is registered with X-rays.

Adult↗
PubMed1997

Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae.

The surface of Streptococcus pneumoniae is decorated with a family of choline-binding proteins (CBPs) that are non-covalently bound to the phosphorylcholine of the teichoic acid. Two examples (PspA, a protective antigen, and LytA, the major autolysin) have been well characterized. We identified additional CPBs and characterized a new CBP, CbpA, as an adhesin and a determinant of virulence. Using choline immobilized on a solid matrix, a mixture of proteins from a pspA-deficient strain of pneumococcus was eluted in a choline-dependent fashion. Antisera to these proteins passively protected mice challenged in the peritoneum with a lethal dose of pneumococci. The predominant component of this mixture, CbpA, is a 75-kDa surface-exposed protein that reacts with human convalescent antisera. The deduced sequence from the corresponding gene showed a chimeric architecture with a unique N-terminal region and a C-terminal domain consisting of 10 repeated choline-binding domains nearly identical to PspA. A cbpA-deficient mutant showed a >50% reduction in adherence to cytokine-activated human cells and failed to bind to immobilized sialic acid or lacto-N-neotetraose, known pneumococcal ligands on eukaryotic cells. Carriage of this mutant in an animal model of nasopharyngeal colonization was reduced 100-fold. There was no difference between the parent strain and this mutant in an intraperitoneal model of sepsis. These data for CbpA extend the important functions of the CBP family to bacterial adherence and identify a pneumococcal vaccine candidate.

Amino Acid Sequence↗
PubMed1997

Feasibility of conducting cardiovascular outcome research in Australian general practice: results from the ANBP2 pilot study. Australian National Blood Pressure Study.

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.

Aged↗
PubMed1997

Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases.

OBJECTIVE: To determine the effect of chronic grapefruit juice administration on steady state blood concentrations of cyclosporine and metabolites in patients with autoimmune diseases. METHODS: 9 patients stabilized on administration of cyclosporine (range 0.7-6.7 mg/kg/day) were given either grapefruit juice or water using randomized crossover design. Whole blood samples were collected before the morning cyclosporine dose and during the 12 h interdose interval. Cyclosporine concentrations were measured using a relatively specific assay (Emit) and total metabolite concentrations were estimated using a nonspecific assay (polyclonal Abbott-TDx). RESULTS: Exposure to grapefruit juice produced significant increases in predose cyclosporine concentrations (p < 0.01) and total metabolite concentrations (p = 0.03) and the area under the cyclosporine and metabolite blood concentration-time curves (p = 0.005, p = 0.001, respectively). One patient developed significant neurological side effects associated with a 68.9 and 214% increase in predose cyclosporine and metabolite concentrations, respectively, during grapefruit juice co-administration. CONCLUSION: Grapefruit juice causes an increase in both parent and metabolite profiles, indicating an alteration in the disposition of cyclosporine and metabolites. This interaction is of potential clinical importance in terms of mechanism, side effects, and dosing.

Adult↗