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J Ross

Publications and source records attributed to J Ross.

At least 55 records · Page 3Linked to original sources
PubMed2001

Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation.

Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

The relationship between suicide and heroin overdose among methadone maintenance patients in Sydney, Australia.

AIMS: To examine the relationship between attempted suicide and non-fatal heroin overdose among methadone maintenance patients. DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: Two hundred and twenty-three methadone maintenance patients. FINDINGS: Forty per cent of participants reported a history of at least one suicide attempt. Females were significantly more likely than males to have attempted suicide (50% vs. 31%), and to have done so on more than one occasion (28% vs. 15%). There was a large difference between males and females in the onset of attempted suicide. Females reported an initial attempt, on average, 6 years earlier than males (18.3 vs. 24.7 years), and were significantly more likely than males to have attempted suicide prior to the onset of heroin use (69% vs. 11%). While heroin overdose was common among the sample (66%), the most common methods employed for suicide attempts were overdose of a non-opioid drug (21%) and slitting of wrists (20%). A deliberate heroin overdose as a means of attempted suicide was reported by 10% of participants. Heroin overdoses appeared overwhelmingly to be accidental. Ninety-two per cent of those who had overdosed reported that their most recent overdose was accidental. CONCLUSIONS: Attempted suicide presents a major clinical problem to staff at drug treatment programmes, but one distinct from heroin overdose. While both overdose and suicide present increasing clinical problems, they are separate problems, and require different responses.

Cross-Sectional Studies↗
PubMed2001

Geographical injecting locations among injecting drug users in Sydney, Australia.

AIMS: To document the geographical injection locations of IDU, and the factors and harms associated with injecting in public places. DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: Two hundred injecting drug users. FINDINGS: Nearly all subjects (96%) had injected in a public place, and 89% had done so in the preceding 6 months. Large proportions had injected in all locations studied, including cars (90%), public toilets (81%), the street (80%) and trains (55%). Injecting in public places also occurred frequently, with 53% of subjects having injected often in at least one public location during the preceding 6 months. Twenty-seven per cent of subjects had injected often in the street over the preceding 6 months, 22% had injected often in cars and 17% had injected often in public toilets. Frequent injectors in public places were more likely to be male, and to have overdosed in the preceding 6 months, injected significantly more drug classes in the preceding 6 months, injected in more bodily injecting sites in the preceding 6 months and had more current injection-related problems than other IDU. CONCLUSIONS: Injecting in public places was practiced by the overwhelming majority of the sample, and a pattern of increased harm was associated with frequent public injecting. In attempting to quantify the harm associated with injecting, and to reduce such harm, the locations injections take place in are of major importance.

Adolescent↗
PubMed2001

Back-projection estimates of the number of dependent heroin users in Australia.

AIMS: To plan an appropriate response to heroin use in Australia, good estimates are needed of the numbers of dependent heroin users, the group who are most in need of treatment, most at risk of fatal opioid overdose and most at risk of contracting and transmitting blood-borne viruses. METHODS: Back-projection methods were used to estimate the numbers of people starting dependent heroin injecting in Australia between 1960 and 1997. Separate analyses were based on national opioid overdose deaths and numbers of new entrants to methadone treatment in New South Wales (NSW). Estimates of the rates at which dependent heroin users cease heroin use, commence methadone treatment or die from opioid overdoses were estimated from external data sources. RESULTS: Back-projection estimates derived from opioid overdose deaths indicated that there were 104 000 (lower limit of 72 000 and upper limit of 157 000) people who were heroin dependent in Australia between 1960 and 1997. Of these it was estimated that 67 000 (39 000-120 000) were still heroin dependent at the end of 1997. Back-projection estimates based on numbers of new entrants to methadone treatment in NSW indicated that there were 108 000 (82 000-141 000) heroin-dependent people in Australia between 1960 and 1997, of whom 71 000 (47 000-109 000) were estimated to be heroin dependent at the end of 1997. Both analyses indicated that the number of heroin-dependent people in Australia has increased substantially from the early 1970s onwards. CONCLUSIONS: Back-projection estimates based on analyses of treatment entries and opioid overdose deaths provide an additional method for estimating the numbers of heroin-dependent people in the population. The addition of these methods to existing methods, using different data sources and statistical methods, should improve consensus estimates of the numbers of heroin-dependent people.

Adolescent↗
PubMed2001

Alfentanil-induced epileptiform activity: a simultaneous surface and depth electroencephalographic study in complex partial epilepsy.

PURPOSE: Alfentanil is a high potency mu opiate receptor agonist commonly used during presurgical induction of anesthesia. This and other opiate receptor agonists have demonstrated proconvulsant effects in animals, but these properties have been less consistently demonstrated in humans. Most human scalp EEG studies have failed to demonstrate induction of epileptiform activity with these agents, which is inconsistent with findings using intracranial EEG. Simultaneous scalp and depth EEG recordings have yet to be performed in this setting. The relationship between opiate dose and proconvulsant activity is unclear. METHODS: Simultaneous scalp and depth electrode recordings were performed on five patients with complex partial epilepsy (CPE) who underwent alfentanil anesthesia induction before depth electrode removal. Consecutive equal bolus doses of alfentanil were administered to each patient according to strict time intervals so as to assess their correlation with any induced epileptiform activity. RESULTS: Epileptiform activity was induced by alfentanil in three of five patients. Two of these patients had electrographic seizures. Epileptiform activity was only detected from the depth electrodes, occurring within 2 min of the first bolus dose in all three cases. Further increase or spread of epileptiform activity did not occur despite cumulative bolus doses of alfentanil. CONCLUSIONS: Alfentanil is proconvulsant in patients with CPE. Induced seizures may be subclinical and lack a scalp EEG correlate. There is a complex dose-response relationship. Alfentanil induction of anesthesia should be approached with caution in patients with CPE.

Adult↗
PubMed2001

Should prostate-specific antigen or prostate-specific antigen density be used as the determining factor when deciding which prostates should undergo biopsy during prostate ultrasound.

Prostate ultrasound has been accepted as the appropriate tool for prostate biopsy guidance to determine the presence of prostate cancer if the prostate-specific antigen (PSA) level is not normal. Prostate-specific antigen density (PSAD) has been used to determine if an increased PSA level may be because of benign enlargement of the gland or possible presence of cancer. The specific "cutoff" for PSA and PSAD to delineate which patients are at highest risk has been controversial. We attempted to assess which PSA level or PSAD level should be used. A retrospective analysis of 600 consecutive men, referred for prostate ultrasound and possible biopsy because of an abnormal DRE result or increased PSA level was undertaken. All had prostate volume determined by biplanar endorectal ultrasound. One hundred sixty-six men had cancer confirmed by biopsy. This latter group was further analyzed and was divided into PSA <4.0, PSA 4 to 10, or PSA >10.0 ng/ml. Groups were divided according to those with PSAD <0.10, <0.12, and <0.15 ng/ml. Correlation with Gleason grade of the tumor was made. Of the 166 men with cancer, 15 had PSA levels <4 ng/ml (all palpable), and 81 had PSA levels between 4.0 and 10.0 ng/ml (48 were not palpable by digital rectal examination [DRE]). There were 38 (22.8%) of 166 men with cancer who had a PSAD <0.15. Using the Gleason scoring system, 30 of 38 men had mid-grade or high-grade cancers. Twenty-one (12.6%) of 166 men with cancer had a PSAD <0.12. Of these, 17 of 21 men had mid-grade or high-grade cancers. Fifteen (9.0%) of 166 men with cancer had a PSAD <0.10. Of these, 13 of 15 had mid-grade or high-grade cancer. If the PSA level is more than 4.0 ng/ml, even if no palpable lesion is discerned by DRE, suspicion for the presence of cancer should be raised. The use of PSAD threshold of 0.15 is not inclusive enough to identify clinically important cancer, and it should not be used. Our data demonstrate that 7.9% of men with cancer had a PSAD <0.15 and mid-grade or high-grade, i.e., clinically important, cancer. Although more negative biopsy results will be obtained, we recommend the use of a lower PSAD "cutoff" than the literature has suggested. We recommend that those men with PSA levels more than 4 ng/ml and a PSAD higher than 0.10 should undergo a prostate biopsy to detect clinically important cancer.

Journal Article↗
PubMed2001

Visual inspection of the prostate biopsy specimen: aid to diagnosis and management.

The purpose of this article is to assess if the visual inspection of the prostate biopsy specimen can be used as a guide when deciding whether to attempt to sample another core of tissue from the same area if a less than adequate specimen was obtained during the first attempt. Five hundred thirty-seven specimens from 84 patients, referred because of an increased prostate-specific antigen (PSA) level and/or a suspicious result on digital rectal examination (DRE), were sampled and prospectively graded based on the lack of formation and amount of liquid in the specimen (grade I) compared to a highly rigid, solid core (grade V). Specimens were then fixed in formalin and retrospectively compared, and the pathologic diagnosis was compared with the subjective visual grade assigned to the specimen. Receiver-operator curve techniques were used to quantify the results and to test for statistical significance. Rigid biopsy specimens were cancer, and liquid, formless specimens were benign. Most biopsy specimens were solid, with moderate consistency, and could not be diagnosed accurately by visual inspection. Diagnosis of prostate cancer, despite the use of PSA, DRE, or diagnostic endorectal ultrasound, requires biopsy for definitive confirmation. Although the use of spring-loaded biopsy needles routinely yields good-quality cores of tissue for pathologic analysis, there are many occasions when a less than optimal specimen is obtained. The question of whether a repeat biopsy in that region is indicated always arises. These data suggest that if the initial specimen is grade I or II, repeat biopsy is probably not indicated. If the initial specimen is grade IV or V, repeat biopsy is recommended.

Journal Article↗
PubMed2001

An audit of the impact of introducing microacupuncture into primary care.

In 1997, one of the partners in a general practice in NW London comprising 6,700 patients began using microacupuncture--a very brief form of treatment described by Felix Mann. The computer system used for patient records was modified to allow easy recording of details of acupuncture treatments; the latter being performed opportunistically in standard 10-minute consultations. Over the course of three years, during which time a second partner began using acupuncture, referrals to acute physiotherapy (conditions present for < 3 months) fell by 86%, and referrals to outpatient rheumatology fell by 51%. This is likely to represent a considerable cost saving to the NHS.

Acupuncture Therapy↗
PubMed2001

The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinopathy.

BACKGROUND: There is no disease specific, reliable, and valid clinical measure of Achilles tendinopathy. OBJECTIVE: To develop and test a questionnaire based instrument that would serve as an index of severity of Achilles tendinopathy. METHODS: Item generation, item reduction, item scaling, and pretesting were used to develop a questionnaire to assess the severity of Achilles tendinopathy. The final version consisted of eight questions that measured the domains of pain, function in daily living, and sporting activity. Results range from 0 to 100, where 100 represents the perfect score. Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy (n = 45), presurgical patients with Achilles tendinopathy (n = 14), and two normal control populations (total n = 87). RESULTS: The VISA-A questionnaire had good test-retest (r = 0.93), intrarater (three tests, r = 0.90), and interrater (r = 0.90) reliability as well as good stability when compared one week apart (r = 0.81). The mean (95% confidence interval) VISA-A score in the non-surgical patients was 64 (59-69), in presurgical patients 44 (28-60), and in control subjects it exceeded 96 (94-99). Thus the VISA-A score was higher in non-surgical than presurgical patients (p = 0.02) and higher in control subjects than in both patient populations (p<0.001). CONCLUSIONS: The VISA-A questionnaire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects. The continuous numerical result of the VISA-A questionnaire has the potential to provide utility in both the clinical setting and research. The test is not designed to be diagnostic. Further studies are needed to determine whether the VISA-A score predicts prognosis.

Achilles Tendon↗
PubMed2001

Suppressor of cytokine signaling-3 is a biomechanical stress-inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways.

The gp130 cytokine receptor activates a cardiomyocyte survival pathway during the transition to heart failure following the biomechanical stress of pressure overload. Although gp130 activation is observed transiently during transverse aortic constriction (TAC), its mechanism of inactivation is largely unknown in cardiomyocytes. We show here that suppressor of cytokine signaling 3 (SOCS3), an intrinsic inhibitor of JAK, shows biphasic induction in response to TAC. The induction of SOCS3 was closely correlated with STAT3 phosphorylation, as well as the activation of an embryonic gene program, suggesting that cardiac gp130-JAK signaling is precisely controlled by this endogenous suppressor. In addition to its cytoprotective action, gp130-dependent signaling induces cardiomyocyte hypertrophy. Adenovirus-mediated gene transfer of SOCS3 to ventricular cardiomyocytes completely suppressed both hypertrophy and antiapoptotic phenotypes induced by leukemia inhibitory factor (LIF). To our knowledge, this is the first clear evidence that these two separate cardiomyocyte phenotypes induced by gp130 activation lie downstream of JAK. Three independent signaling pathways, STAT3, MEK1-ERK1/2, and AKT activation, that are coinduced by LIF stimulation were completely suppressed by SOCS3 overexpression. We conclude that SOCS3 is a mechanical stress-inducible gene in cardiac muscle cells and that it directly modulates stress-induced gp130 cytokine receptor signaling as the key molecular switch for a negative feedback circuit for both myocyte hypertrophy and survival.

Animals↗
PubMed2001

Diving accidents in sports divers in Orkney waters.

Scapa Flow in Orkney is one of the major world centres for wreck diving. Because of the geography of Orkney and the nature of the diving, it is possible to make relatively accurate estimates of the number of dives taking place. The denominator of dive activity allows the unusual opportunity of precise calculation of accident rates. In 1999, one in every 178 sports divers visiting Orkney was involved in a significant accident, in 2000 the figure was one in 102. Some of these accidents appear to have been predictable and could be avoided by better education and preparation of visiting divers.

Athletic Injuries↗
PubMed2001

[Monetary value of breast milk in Bolivia].

OBJECTIVE: To estimate the volume of breast milk consumed by Bolivian children under 36 months of age, and the monetary value of replacing that volume of breast milk with commercial substitutes. METHODS: The analysis took into account the distribution of the infant population by age groups, the prevalence of breast-feeding practices (exclusive or partial) in every age group, the average volume of breast milk consumed by the infants of a given age group, and the cost of breast milk production and replacement. RESULTS: Bolivian infants annually consume more than 161 million liters of breast milk, which represents an average volume of 573 mL/day per infant under 1 year of age. The monetary value of breast milk consumed by the Bolivian infants amounts to US$ 274 million annually. The average cost of replacing breast milk with commercial substitutes for an infant adequately breast-fed for the first year of life would be US$ 407. DISCUSSION: For the formulation and consolidation of policies and programs to protect, promote, and support breast-feeding to become a reality, it is necessary that the political leaders of Bolivia be aware of the enormous monetary value of breast milk.

Bolivia↗
PubMed2000

Heroin-related deaths in New South Wales, Australia, 1992-1996.

The coronial files of all heroin-related fatalities that occurred in New South Wales (NSW) over the period 1992-1996 were inspected. There were 953 heroin-related fatalities in NSW over the study period. There was a substantial, statistically significant increase in heroin-related fatalities over the study period, from 152 deaths in 1992 to 226 during 1996. The mean age of cases was 31.0 years, 85% were male, and 85% were classified as dependent on heroin at the time of death. There was a significant increase in the age of cases over the study period and the proportion of cases that were employed. Fatalities predominantly occurred in home settings (61%). No intervention occurred in 79% of cases. Fifty deaths (5%) occurred in the month following release from prison, 16 of which occurred the first 24 hours after release. Morphine concentrations rose from 0.24 mg/l in 1992 to 0.38 mg/l in 1996. Seventy six percent of cases involved heroin in combination with other drugs: alcohol (46%), benzodiazepines (27%), antidepressants (7%) and cocaine (7%). In only 24% of cases was morphine the sole drug detected. Males were significantly more likely to have alcohol detected at autopsy (49 vs. 24%), while females were more likely to have benzodiazepines detected (41 vs. 17%). The median blood morphine concentration among cases in which alcohol was detected was significantly lower than other cases (0.27 vs. 0.39 mg/l). It is concluded that heroin-related deaths continued to rise throughout the study period, and that deaths were predominantly among older, untreated males. Despite the rise in blood morphine concentrations, polydrug use remained the predominant toxicological pattern.

Adolescent↗
PubMed2000

Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch for the destruction of p27Xic1.

The action of cyclin-dependent kinases (CDKs) is regulated by phosphorylation, cyclin levels, the abundance of CDK inhibitors, and, as recently has been shown for cyclin B/cdc2, their localization. It is unclear how localization regulates the action of cyclin E/Cdk2 and its inhibitors. Here, we show that the closest known Xenopus laevis homolog of mammalian Cdk2 inhibitors p27(Kip1) and p21(CIP1), Xic1, is concentrated, ubiquitinated, and destroyed in the nucleus. Furthermore, Xic1 destruction requires nuclear import, but not nuclear export, and requires the formation of a transport-competent nuclear envelope, but not interactions between the lamina and chromatin. We show that (i) cyclin E/Cdk2 and Xic1 are transported into the nucleus as a complex and that Xic1 destruction requires the activity of cyclin E, (ii) that phosphorylation of Xic1 by cyclin E/Cdk2 bypasses the requirement for nuclear formation, and (iii) that the phosphorylation of Xic1 by cyclin E/Cdk2 is concentration dependent and likely realized through second-order interactions between stable cyclin E/Cdk2/Xic1 ternary complexes. Based on these results we propose a model wherein nuclear accumulation of the cyclin E/Cdk2/Xic1 complex triggers a concentration-dependent switch that promotes the phosphorylation of Xic1 and, consequently, its ubiquitination and destruction, thus allowing subsequent activation of cyclin E/Cdk2.

Biological Transport↗
PubMed2000

Coherent global motion in the absence of coherent velocity signals.

It is widely believed that form and motion are analysed separately in mammalian visual systems. Form is confined within a stream that projects ventrally from V1 to the inferotemporal cortex, and motion within a stream that projects more dorsally, to the posterior parietal cortex [1] [2] [3] [4] [5] [6] [7]. Current descriptions suggest that there is little contact between the two streams until the products of their separate analyses are bound together at a late (and still unidentified) stage in perception [3] [8] [9] [10]. There are, however, indications that form and motion signals may interact [11], and that form signals, streaks derived from motion, may assist in the analysis of its direction [12]. Lennie [13] proposes that all image attributes, form and motion included, remain intimately coupled within the same retinotopic map at all stages of visual analysis. Here we show that form, independent of motion, can give coherence to incoherent motion. Sequences of Glass patterns [14] built to a common global rule are devoid of coherent motion signals, but they produce motion consistent with the global rule for form, not with the random velocity components of the pattern sequence.

Animals↗