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Biomedical subjects

L Johns

Publications and source records attributed to L Johns.

At least 19 recordsLinked to original sources
PubMed2006

The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk.

The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45-69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were > or =4 ng ml(-1) and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.

Age of Onset↗
PubMed2005

Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years.

Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50-52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme.

Adult↗
PubMed2003

Effects of bilobalide on cerebral amino acid neurotransmission.

Bilobalide is one of many active constituents found in EGb 761 (definition see editorial), which is extracted from Ginkgo biloba leaves. Whilst there is good, sound evidence that bilobalide exhibits neuroprotective actions in a variety of model systems, there is currently no consensus on its mechanism of action. This present communication summarises the results we have obtained with this compound on excitatory amino acid neurotransmission in the central nervous system using both neurochemical and electrophysiological techniques. Bilobalide was shown to reduce glutamate and aspartate release elicited by both high potassium-containing artificial cerebrospinal fluid (aCSF) or veratridine from mouse cortical slices. In addition, bilobalide had a very potent effect (IC (50) 2.7 microM) on glutamate release elicited by hypoxia/hypoglycaemia-induced release from rat cortical slices. Electrophysiologically, bilobalide also decreased the frequency of gamma-aminobutyric acid (GABA) uptake inhibitor-induced depolarisations in mouse cortical slices, an effect probably mediated by a decrease in glutamate release. No definitive conclusions can be reached concerning the mechanism of action of bilobalide, but an ability to decrease excitotoxic amino acid release, particularly glutamate, would suggest that this is a probable mechanism to account for its neuroprotective properties.

Animals↗
PubMed2001

Variable stereochemistry in highly branched isoprenoids from diatoms.

C(25) highly branched isoprenoid (HBI) alkenes are ubiquitous lipids found in geochemical samples around the globe. The origins of these widespread geochemicals are believed to be restricted to a limited number of diatoms, including Haslea ostrearia (and related species), Rhizosolenia setigera, and Pleurosigma intermedium. The unsaturation of the HBI alkenes ranges from 2-6 in different species and cultures. The number of stereogenic centres is usually limited to two in the HBI alkenes due to double bond positions. The relative and/or absolute configurations for these have been determined for a range of HBI alkenes produced from different diatoms cultured under a number of growth conditions. These determinations have involved a combined spectroscopic and chromatographic analysis using NMR spectroscopy and chiral gas chromatography, respectively. HBIs isolated from Haslea spp. belong to a specific structural type which exhibit configurational diastereoisomerism, while those isolated from P. intermedium and R. setigera represent a different structural type and usually exist as mixtures of geometric isomers only. HBIs are reported from a new species of diatom whose stereochemical properties lie between those found for Haslea spp. and P. intermedium.

Alkenes↗
PubMed2001

Vasospasm in monkeys resolves because of loss of and encasement of subarachnoid blood clot.

BACKGROUND AND PURPOSE: We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH). METHODS: Monkeys underwent angiography and right (n=17) or bilateral (n=8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5, and 7 days later. Animals with right SAH underwent angiography 7 days later. The clot was then not removed (n=5), removed and replaced with fresh clot (n=7), or removed and not replaced (n=5). At the same time on day 7, the removed clot (n=12) or fresh clot (n=5) was placed on the left side. Angiography was repeated every 2 days until day 14. RESULTS: SAH caused significant vasospasm on day 7 that resolved by day 14. Removal of clot on day 7 resulted in more rapid resolution of vasospasm. Placement of fresh clot onto arteries that had already been exposed to clot for 7 days produced vasospasm that persisted without resolving for an additional 7 days. Placement of 7-day-old clot from the right onto previously unexposed left arteries or of clot from blood removed from an animal 7 days after SAH caused significantly more rapid onset of vasospasm compared with de novo vasospasm. Microscopic examination of the clots showed they were surrounded by macrophages 7 days after SAH. Arterial compliance and contractility were reduced in relation to duration of the exposure of arteries to clot. CONCLUSIONS: Vasospasm resolves because of loss of subarachnoid blood clot. We hypothesize that reduced spasmogen release from the clot contributes to resolution of vasospasm. There was no response in the cerebral arteries that rendered them less responsive to the subarachnoid clot.

Analysis of Variance↗
PubMed2000

Hypoxia/hypoglycemia-induced amino acid release is decreased in vitro by preconditioning.

The aim of this study was to investigate the effects of preconditioning on amino acid neurotransmitter release, induced by hypoxia/hypoglycaemia, from rat brain cortical slices. Tissue, perfused with artificial cerebrospinal fluid (aCSF) at 37 degrees C with zero glucose and gassed with 95% nitrogen and 5% carbon dioxide, showed a fivefold increase in glutamate release with little effect on gamma-aminobutyric acid (GABA) release. Preconditioning, with three 5-min periods of hypoxia/hypoglycaemia preceding continuous hypoxia/hypoglycaemia, significantly decreased glutamate release whilst significantly elevating GABA release. These results suggest that GABA may reduce the release of glutamate and consequently decrease the neurotoxic effects of glutamate.

Amino Acids↗
PubMed2000

Configurations of polyunsaturated sesterterpenoids from the diatom, Haslea ostrearia.

The partial configurations of C25 isoprenoid alkenes isolated from the diatom Haslea ostrearia Gaillon (Simonsen) have been established. A combination of NMR spectroscopy studies of the alkenes with chiral shift reagents in conjunction with soluble silver beta-diketonate complexes and enantioselective gas chromatography of oxidation products of the alkenes was used. Unexpected differences in highly branched isoprenoid isomer configurations were observed between different laboratory cultures of the alga.

Alkenes↗
PubMed2000

Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys.

Hemoglobin is a key factor in the production of cerebral vasospasm. Metabolism of hemoglobin involves breakdown of heme by heme oxygenase (HO) and sequestration of the released iron in ferritin. We determined whether subarachnoid hemorrhage induces these proteins in cerebral arteries and, if so, in which cells they are produced. Whether the changes correlated with vasospasm also was investigated. Subarachnoid hemorrhage was created in monkeys, and vasospasm was assessed by angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage. Ferritin and HO-1 messenger ribonucleic acid (mRNA) and protein were measured by competitive reverse transcription-polymerase chain reaction and Western blotting in hemorrhage-side and control-side cerebral arteries and brain tissue. The location of these proteins was determined by immunohistochemistry. There was significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage. There were no significant changes in mRNA for HO-1 or ferritin in cerebral arteries or brain tissue at any time. There was a significant increase in HO-1 and ferritin protein in hemorrhage-side compared with control-side cerebral arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3 days, whereas the increase in ferritin protein was maximal at 7 days. There was no detectable increase in HO-1 or ferritin protein in brain tissue at any time. Immunohistochemistry localized HO-1 protein and ferritin to cells in the adventitia of the arterial wall. We show that subarachnoid hemorrhage is associated with a significant increase in HO-1 and ferritin proteins in cerebral arteries that begins at least as early as 3 days after the hemorrhage and that persists for up to 14 days.

Animals↗
PubMed2000

Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries.

OBJECT: It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue. METHODS: To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7. CONCLUSIONS: The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.

Adaptation, Physiological↗
PubMed1998

U74389G prevents vasospasm after subarachnoid hemorrhage in dogs.

OBJECTIVE: Oxygen-derived free radicals may contribute to vasospasm after the rupture of an intracranial aneurysm through direct vasoconstricting effects occurring within the arterial wall or, secondarily, by causing lipid peroxidation in the subarachnoid erythrocytes with secondary induction of vasoconstriction. U74389G is a potent inhibitor of lipid peroxidation and a scavenger of oxygen-derived free radicals. This study determined the relative contributions of oxygen-derived free radicals and lipid peroxidation to vasospasm in the double-hemorrhage dog model. METHODS: Sixteen dogs underwent baseline (Day 0) cerebral angiography and induction of subarachnoid hemorrhage by two injections of blood into the cisterna magna 2 days apart. They were randomized to receive drug vehicle (n=8) or U74389G (n=8, 3 mg/kg of body weight/d) intravenously. Drug administration and end point analysis were blinded. The end points were angiographic vasospasm, as assessed by comparison of angiograms obtained before and 7 days after subarachnoid hemorrhage, and the levels of malondialdehyde and salicylate hydroxylation products (dihydroxybenzoic acids) in cerebrospinal fluid and of malondialdehyde in subarachnoid blood clots and basilar arteries 7 days after hemorrhage. RESULTS: Comparisons within groups of Day 0 and Day 7 angiograms and between groups of angiograms obtained at Day 7, showed significant vasospasm in animals in the vehicle group (mean+/-standard error, 51%+/-4) but not in the U74389G group (25%+/-11, P < 0.05, unpaired t test). High-pressure liquid chromatographic assays of malondialdehyde and dihydroxybenzoic acids in cerebrospinal fluid, subarachnoid blood clots, and basilar arteries showed no significant differences between groups. CONCLUSION: The significant prevention of vasospasm by U74389G without change in levels of indicators of free radical reactions suggests that the effect of the drug is related to other processes occurring in the arterial wall and that cerebrospinal fluid levels of oxygen radicals and lipid peroxides are not useful markers of vasospasm.

Animals↗
PubMed1998

Randomized comparison of Guglielmi detachable coils and cellulose acetate polymer for treatment of aneurysms in dogs.

BACKGROUND AND PURPOSE: Endovascular treatments for aneurysms are being used more frequently in patients in the absence of a large body of information on their histopathological effects. This study determined the efficacy and histopathological effects of treatment of experimental aneurysms with Guglielmi detachable coils (GDC) or cellulose acetate polymer (CAP). METHODS: Fourteen dogs had 13 terminal and 30 sidewall aneurysms created with venous pouches sutured to the cervical carotid arteries. Two weeks later, dogs had angiography followed by randomization to no treatment (n=2) or to aneurysm occlusion with GDC (n=4) or CAP (n=6). Two months later, angiography was repeated, animals were killed, and aneurysms were excised, fixed, photographed, and examined by light and electron microscopy. RESULTS: Two dogs were excluded because of common carotid artery occlusion at 2-week angiography. There were 11 terminal and 16 sidewall aneurysms available for treatment. The rate of spontaneous thrombosis of untreated aneurysms was 0% (0/5). Treatment with GDC showed complete terminal and sidewall aneurysm obliteration rates of 33% (1/3) and 80% (4/5), respectively. Greater than 90% occlusion occurred in the remaining cases. There were no parent or branch artery occlusions. Treatment with CAP showed complete terminal and sidewall aneurysm obliteration rates of 20% (1/5) and 0% (0/5), respectively, and incomplete sidewall aneurysm obliteration in 1 of 5 cases. Aneurysms reformed at 2 months in 2 of 5 terminal and 1 of 5 sidewall cases. There were parent or branch artery occlusions with CAP in 2 and 4 cases, respectively. The rate of aneurysm occlusion was significantly lower and the rate of arterial occlusion significantly higher with CAP than with GDC (P<.05). Histopathology showed complete endothelialization across the orifice of the aneurysm successfully treated with CAP, whereas aneurysms treated with GDC were significantly more likely to show fresh or organizing thrombus without complete endothelialization (P<.05). CONCLUSIONS: It is concluded that both treatments have limitations. Complete packing of aneurysms with GDC obliterates the aneurysm, but endothelialization does not always occur within 2 months. There are substantial problems with CAP. It is thrombogenic and carries a higher risk of causing arterial thrombosis. Even if an aneurysm is successfully obliterated initially with CAP, the CAP may disappear, leaving the aneurysm completely untreated.

Animals↗
PubMed1998

Prevention of vasospasm after subarachnoid hemorrhage in dogs by continuous intravenous infusion of PD156707.

This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitive antagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs. Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterial blood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuous infusion of drug vehicle (n = 10) or PD156707 (n = 12). Cisternal blood injection was repeated on day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) on days 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed. Analysis of physiological variables within (analysis of variance) groups across time and between (unpaired t-test) groups at each time showed that drug-treated animals had significantly increased heart rate on day 7 compared to day 0 (p < 0.005). Comparison of basilar artery diameters at day 7 showed that PD156707 significantly decreased the degree of basilar artery vasospasm (placebo: -47 +/- 5% reduction [mean +/- SE] versus PD156707: -28 +/- 7%, p < 0.05, unpaired t-test). There was, however, significant vasospasm when comparing within groups (paired t-test, placebo: p < 0.0001, PD156707: p < 0.005). Mean plasma PD156707 levels (322 +/- 123 ng/ml) were adequate to block responses of endothelin-1 on endothelin A receptors in vitro although CSF levels (11 +/- 7 ng/ml) were substantially lower. Infusion of PD156707 into the basilar artery on day 7 caused a small but significant 10 +/- 3% (paired t-test, p < 0.01) increase in diameter compared to placebo (3 +/- 3% increase, p = 0.32). This infusion also was associated with a substantial increase in CSF drug levels to 19 +/- 9 mg/ml. These results suggest that endothelin A receptors mediate some of the vasospasm that occurs after SAH in dogs and that blockade of these receptors may be a beneficial treatment for vasospasm.

Animals↗
PubMed1997

Developing capacities of youth as lay health advisors: a case study with high school students.

Youth lay health advising, a form of support or helping, is an important potential resource for preventive intervention. This article describes a case study of a youth lay health advising program designed to provide high school students with support and guidance to handle challenges and concerns related to their health and quality of life. First, the planning, program development, and implementation of the approach are described. Second, a rapid formative evaluation presents quantitative and qualitative information on adolescent issues faced, the types and content of interactions, and peer helper satisfaction with the program. Third, the strengths and challenges of the peer helping program and the role of youth as lay health advisors are discussed. The article concludes with a discussion of the implications for practitioners on this approach to building the capacity of adolescents as lay advisors for community health.

Adolescent↗
PubMed1995

Emboli enter penetrating arteries of monkey brain in relation to their size.

BACKGROUND AND PURPOSE: Controversy exists regarding whether lacunar infarction is due to embolism or whether it is always due to lipohyalinosis of small penetrating arteries. We hypothesized that emboli can enter penetrating arteries in relation to the blood flow to these arteries and to the diameter of the emboli. METHODS: We injected agarose spheres of three different mean diameters (31 +/- 4, 68 +/- 14, and 92 +/- 28 microns [n = 50 for each]) into one internal carotid artery of 3 monkeys for each sphere size (total, n = 9 monkeys). After injection of spheres, monkeys were killed, the brains were removed and fixed in formalin, and serial hematoxylin and eosin sections of three coronal sections of the cerebrum were examined by light microscopy. Sphere diameter (n = 25 for each territory and sphere size) and distribution in circumferential and penetrating artery territories were measured with the use of an image analyzer. Corrections were made for shrinkage of spheres during fixation and for the effect of random sampling of 10-microns sections through spheres of different diameter. RESULTS: Mean numbers of spheres for each size were significantly higher in circumferential than penetrating artery territories (P < .05, t test). When correction was made for the volume of brain supplied by each territory, there was no significant difference in the number of spheres in circumferential versus penetrating artery territories for the two smaller sphere sizes. For spheres of mean diameter of 92 microns, significantly more spheres entered circumferential rather than penetrating artery territories (P < .05, t test). The percentage of the total number of spheres that entered penetrating artery territories was 5%, 6%, and 1.4% for beads of 31 +/- 4, 68 +/- 14, and 92 +/- 28 microns mean diameter, respectively. CONCLUSIONS: Small emboli can enter penetrating arteries and could therefore produce lacunar infarction. The majority of emboli, however, enter circumferential arteries. The larger the emboli, the more likely that they will enter circumferential arteries rather than penetrating arteries.

Acrylic Resins↗
PubMed1995

Results from the NHS breast screening programme 1990-1993.

OBJECTIVE: To present results from the NHS breast screening programme (NHSBSP) for the three year period 1990 to 1993, and to examine the extent to which interim targets are being met. METHODS: Data have been collated from all screening programmes in the United Kingdom on standard "Korner" returns, supplemented for the year 1991/92 by data from the radiology quality assurance programme. Most of the data refer to the prevalent screening round, but some data on rescreening are also available. RESULTS: The total cancer detection rate at prevalent screens was 6.0/1000, 18% being in situ cancers; the detection rate of invasive cancers < or = 10 mm in diameter was 1.3/1000, but data on size were missing for 12% of cancers. Referral rates were significantly lower for programmes using two view mammography at the prevalent screen than for those using single view, and cancer detection rates were significantly higher. For prevalent screens over the three year period, 70% of programmes had a referral rate of < or = 7%, 87% had a benign biopsy rate of < or = 5/1000, and 79% had a cancer detection rate of > or = 5/1000. By contrast, only 30% of programmes appeared to meet the target detection rate of > 1.5/1000 for invasive cancers < or = 10 mm in diameter. CONCLUSIONS: While the majority of interim targets are being met by the NHSBSP, the rate of detection of small invasive cancers requires careful monitoring. Collection of more accurate data on size of cancers and interval cancer rates will give a better indication of progress towards the target mortality reduction.

Aged↗