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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 127 records · Page 7Linked to original sources

Retinoic acid alters the mechanism of attachment of malignant astrocytoma and neuroblastoma cells to thrombospondin-1.

Based on the hypothesis that the attachment of neuroectodermal cells to thrombospondin-1 (TSP-1) may affect tumor spread and play a role in the anti-tumor effects of retinoic acid, we investigated the expression of TSP-1 in these cells in situ and the effect of retinoic acid on the morphology of TSP-1-adherent neuroblastoma (SK-N-SH) and malignant astrocytoma (U-251MG) cells in vitro. TSP-1-adherent SK-N-SH cells demonstrated process outgrowth, with further neuronal differentiation after retinoic acid treatment, consistent with the in situ studies showing that TSP-1 expression occurs in a differentiation-specific manner in neuroblastic tumors. TSP-1-adherent U-251MG cells failed to spread; however, after retinoic acid treatment the cells demonstrated broad lamellipodia containing radial actin fibers and organization of integrins alpha3beta1 and alpha5beta1 in clusters in lamellipodia and filopodia. The attachment of both SK-N-SH and U-251MG cells to TSP-1 was found to be mediated by heparan sulfate proteoglycans, integrins, and the CLESH-1 adhesion domain first identified in CD36. Heparin and heparitinase treatment inhibited TSP-1 attachment. Integrins alpha3beta1 and alpha5beta1 mediated TSP-1 attachment of SK-N-SH cells, and integrins alpha3beta1, alpha5beta1, and alphavbeta3 mediated TSP-1 attachment of U-251MG cells. Attachment was dependent on the RGD sequence which is located in the carboxy-terminus of TSP-1. Treatment with a pharmacologic dosage of retinoic acid altered the TSP-1 cell adhesion mechanism in both cell lines in that neither heparin nor micromolar concentrations of the RGD peptide inhibited attachment; after treatment, attachment was inhibited by the CSVTCG peptide located in the type I repeat domain of TSP-1 and a recombinant adhesion domain (CLESH-1) from CD36. Expression of CD36 was found in the retinoic acid-treated U-251MG cells. These data indicate that neuroectodermally derived cells utilize several mechanisms to attach to TSP-1, and these are differentially modulated by treatment with retinoic acid. These data also suggest that the CSVTCG sequence of TSP-1 modulates or directs cytoskeletal organization in neuroblastoma and astrocytoma cells.

Astrocytes↗

Meningococcal disease in Auckland, July 1992 - June 1994.

AIMS: To assess two years of meningococcal disease in the Auckland area, the outcomes and management issues, and the specific socio-geographic groups that are affected. METHODS: Using the nationally agreed case definition, a retrospective chart review was undertaken. Case finding was through the National surveillance system at ESR, backed by hospital laboratory and coroner case findings. RESULTS: There were 106 cases of meningococcal disease, both adult and paediatric, from July 1992 to June 1994. Group B (n=61), was predominant throughout this period especially in the winter months. There were two main age groups most affected. The first, and most striking, was in Maori and New Zealand Pacific Island children younger than five years, with rates of 52.6 and 54.2/100,000 respectively. The second peak was in European, and to a lesser extent Maori, 15-24 year-olds, (rates 11.7 and 8.5/100,000, respectively). The annual incidence was 5.6/100,000 with an overall case fatality rate of 6.6%, (n=7). South Auckland had the greatest proportion of cases with 42/106. Two-thirds of the cases were referred for hospital admission by a general practitioner. From both general practitioner and self-referred groups, two-thirds had a petechial/purpuric rash on arrival at hospital. For general practitioner referred cases, 24 received parenteral antibiotics on referral, and from these cases there was one death, (1/24). Those not treated with antibiotics (general practitioner or self-referred) had a mortality of 2/41. There were 31 cases of paediatric meningococcal meningitis. Nineteen cases had dexamethasone in appropriate dose and timing; no hearing loss occurred in the 17 cases that survived (0/17), compared to 2/12 not treated with dexamethasone. This compares to a published rate of 5-7%. CONCLUSIONS: Meningococcal disease, predominantly serogroup B, is of high incidence in Auckland. The highest rates of disease are occurring in the under five-year-olds, where an effective group B vaccine is awaited. The benefit of dexamethasone is suggestive. There was no clear benefit in outcome by pre-treatment with parenteral antibiotics for paediatric meningococcal disease though no suggestive detrimental effect either.

Adolescent↗

Stress reinstates nicotine seeking but not sucrose solution seeking in rats.

RATIONALE: Intermittent footshock stress effectively reinstates extinguished heroin-, cocaine- and alcohol-taking behaviors, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of the phenomenon of stress-induced reinstatement by determining the effect of footshock on reinstatement of operant responding previously maintained by nicotine or palatable sucrose solutions. METHODS: Groups of rats were trained to self-administer either nicotine (0.03 mg/kg per infusion, 14 days) or sucrose (10 or 30% w/v, 14-20 days). After extinction of the nicotine- or the sucrose-reinforced behaviors for 5-15 days, the rats were exposed to intermittent footshock stress (5 and 15 min, 0.8 mA) during tests for reinstatement. RESULTS: Footshock reliably reinstated nicotine seeking after extinction of the drug-reinforced behavior. In contrast, the same parameters of footshock stress did not consistently reinstate operant responding previously maintained by sucrose solutions. CONCLUSIONS: These and previous data suggest that stressors may be more effective stimuli for reinstatement of behaviors previously maintained by drug reinforcers as compared with non-drug reinforcers.

Animals↗

Regulation of cytochrome P450 expression by sphingolipids.

Sphingolipids modulate many aspects of cell function, including the expression of cytochrome P450, a superfamily of heme proteins that participate in the oxidation of a wide range of compounds of both endogenous (steroid hormones and other lipids) and exogenous (e.g. alcohol, drugs and environmental pollutants) origin. Cytochrome P450-2C11 (CYP 2C11) is down-regulated in response to interleukin-1beta (IL-1beta), and this response involves the hydrolysis of sphingomyelin to ceramide as well as ceramide to sphingosine, and phosphorylation of sphingosine to sphingosine 1-phosphate. Activation of ceramidase(s) are a key determinant of which bioactive sphingolipid metabolites are formed in response to IL-1beta. Ceramidase activation also appears to account for the loss of expression of CYP 2C11 when hepatocytes are placed in cell culture, and the restoration of expression when they are plated on Matrigel; hence, this pathway is influenced by, and may mediate, interactions between hepatocytes and the extracellular matrix. Recent studies using inhibitors of sphingolipid metabolism have discovered that sphingolipids are also required for the induction of CYP1A1 by 3-methylcholanthrene, however, in this case, the requirement is for de novo sphingolipid biosynthesis rather than the turnover of complex sphingolipids. These findings illustrate how changes in sphingolipid metabolism can influence the regulation of at least several isoforms of cytochrome P450.

Animals↗

The role of dopamine in the nucleus accumbens in analgesia.

Opioid and psychostimulant drugs have long been used for the relief of chronic pain in the clinical situation. Animal studies confirm that these drugs alleviate persistent or tonic pain. Little is known, however, about the neural systems underlying the suppression of tonic pain except that they are different from those mediating the suppression of phasic (i.e., sharp and short-lasting) pain. Although spinal and brainstem-descending pain suppression mechanisms play a role in mediating the inhibition of tonic pain, it appears that this response is additionally mediated by the activation of mechanisms lying rostral to the brainstem. Recent studies suggest that the activation of mesolimbic dopamine (DA) neurons, arising from the cell bodies of the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAcc), plays an important role in mediating the suppression of tonic pain. Other studies suggest that this pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, through the endogenous release of opioids and substance P (SP) in the midbrain.

Analgesics, Opioid↗

The tachykinin NK-1 receptor antagonist, RP-67580, infused into the ventral tegmental area prevents stress-induced analgesia in the formalin test.

Substance P (SP) receptors in the ventral tegmental area (VTA) play a critical role in mediating the stress-induced activation of midbrain ascending dopamine (DA) neurons. Interestingly, SP acting in the VTA induces analgesia in the formalin test for tonic pain. Because exposure to stress inhibits pain in this test, we speculated that SP receptors in the VTA might mediate stress-induced analgesia. The present study explored this idea by examining the effect of blocking tachykinin NK-1 receptors in the VTA on footshock stress-induced analgesia in the formalin test. Intra-VTA infusions of the novel tachykinin NK-1 receptor antagonist, RP-67580, prevented this response. This finding suggests that exposure to stress inhibits tonic pain through the release of endogenous SP in the VTA.

Analgesics↗

The efficacy and safety of fexofenadine HCl and pseudoephedrine, alone and in combination, in seasonal allergic rhinitis.

BACKGROUND: Antihistamines effectively treat seasonal allergic rhinitis (SAR), although the ability of this drug class to reduce nasal congestion is limited. Nasal decongestants effectively treat nasal congestion but not the histamine-related components of SAR. Therefore antihistamine/nasal decongestant combinations are commonly used to maximize the treatment of SAR. Fexofenadine HCl is a nonsedating, long-acting H1 receptor antagonist that provides fast and effective relief from SAR. It is well tolerated, with no sedative or cardiotoxic effects. OBJECTIVE: We sought to compare the efficacy and safety of a fexofenadine HCl/pseudoephedrine HCl combination with that of each individual component in the treatment of ragweed allergy. METHODS: In this Canadian multicenter, double-blind, parallel-group study, 651 patients allergic to ragweed were randomized to receive 60 mg of fexofenadine HCl twice daily, 120 mg of sustained-release pseudoephedrine HCl twice daily, or a combination of the 2 drugs (60 mg of fexofenadine HCl/120 mg of sustained-release pseudoephedrine HCl) twice daily for 2 weeks. Efficacy analyses were based on symptom severity. In addition, a health economic assessment was performed. RESULTS: Combination therapy was significantly more effective than pseudoephedrine alone in improving primarily histamine-mediated symptoms (sneezing; rhinorrhea; itchy nose, palate, and/or throat; and itchy, watery, red eyes) and significantly more effective than fexofenadine alone in reducing nasal congestion. Combination therapy also produced greater improvements in daily activities and work productivity compared with the individual components. No serious adverse events were reported in any of the treatment groups. In addition, no clinically significant changes in 12-lead electrocardiogram parameters, vital signs, or clinical laboratory values were observed. CONCLUSION: Combination therapy is more effective than fexofenadine alone or pseudoephedrine alone in relieving the full spectrum of SAR symptoms (ie, both the primarily histamine-related symptoms and nasal congestion).

Adolescent↗

Link between patient preferences and treatment outcomes in seasonal allergic rhinitis: an empiric investigation.

In a multicenter, parallel-group, double-masked, randomized study, two questionnaires were administered to a clinical study population to identify which specific symptoms of seasonal allergic rhinitis patients perceived as most important to relieve (personal preferences) and to learn whether any relationship existed between patient preferences and the severity of their symptoms during treatment with antihistamines. The group was composed of 256 males and 313 females. Their mean age was 32.4 years, and mean duration of seasonal allergic rhinitis was 14.5 years, with mean age of onset of 17.7 years. After receiving placebo for 1 week, patients were randomly allocated to receive an antihistamine (fexofenadine or loratadine) for 2 weeks. Patient preferences for relief of individual allergy symptoms (rhinitis; sneezing; itchy, watery, red eyes; itchy nose, palate, or throat) and related conditions (fatigue, physical limitations) were scored using 2 different questionnaires before treatment (0-to-10 category rating scale for assessing the 4 symptoms of allergic rhinitis) and after receiving placebo for 1 week (Feeling Thermometer). Symptom severity was reported in patient diaries after 1 and 2 weeks of antihistamine treatment and was measured by patient self-assessment. All symptoms were considered by the patients to be important to relieve, the most important being itchy, watery, red eyes and rhinorrhea. The severity of allergy symptoms was consistently related to the importance of symptoms identified before treatment. Therefore, including patient preferences in medical evaluations might be a useful tool in evaluating the success of their treatment.

Adult↗

Detection of t(12;21) in childhood acute lymphoblastic leukemia by fluorescence in situ hybridization.

Metaphase preparations from 36 patients with acute lymphoblastic leukemia (ALL) have been retrospectively screened by fluorescence in situ hybridization (FISH) to determine the incidence of translocation (12;21) and the potential usefulness of FISH as an adjunct to conventional cytogenetic analysis. With the use of specific chromosome paints, 4 of 31 patients with B-lineage childhood ALL (13%) demonstrated rearrangements of chromosomes 12 and 21, and therefore, were considered to harbor the translocation, which had not previously been detected by conventional karyotyping. However, none of these positive cases revealed the standard reciprocal t(12;21)(p12;q22) as the sole abnormality involving chromosomes 12 and 21. The study confirms the feasibility and advantages of introducing FISH screening for t(12;21) in pediatric ALL cases and demonstrates the usefulness of FISH screening as a backup to concurrent cytogenetic analysis to resolve variant translocations and aberrant results. The presence of t(12;21) has also been correlated to clinical data to assess the prognostic significance of this translocation on its own or in association with other prognostic features.

Adolescent↗

Long-lasting sensitization to the accelerating effects of amphetamine on the speed of an internal clock.

Drinking in the rat occurs in bursts of rapid licking, a high frequency rhythmic behavior controlled by a neural clock located in the brain stem. We found that 3.0 mg/kg amphetamine increased the speed of licking and shifted to the left the frequency distribution of inter-lick intervals. Repeated amphetamine treatments result in long-lasting sensitization to this effect. Thus, it appears possible to produce enduring changes in the activity of a biological interval clock (or 'stopwatch') by manipulating catecholaminergic transmission. These findings may be important for an understanding of the neural basis of normal and pathological timing behavior.

Amphetamine↗

The effects of gonadal hormones on the development and expression of the stimulant effects of morphine in male and female rats.

Previous studies have shown that the behavioral activating effects of the stimulant drug amphetamine are augmented in female rats by estradiol. Here we studied the effects of gonadectomy and gonadal hormone replacement on the stimulant effects of morphine in both females and males. Groups of intact, ovariectomized (Ovex), and Ovex females given estradiol benzoate (EB) (5 micrograms), and groups of intact, castrated, and castrated males given testosterone propionate (30 micrograms) were administered five injections of morphine sulphate (10 mg/kg, i.p.) or saline at 3-day intervals. Activity was monitored on each occasion for 2 h. Among females treated with morphine, intact and Ovex-EB animals showed progressive enhancement of activity over sessions, whereas Ovex animals showed no change. Three days after the last pre-exposure session, all animals received 5 mg/kg morphine in a test for sensitization. In spite of the lower levels of activity in Ovex animals, animals from all groups previously exposed to morphine showed a sensitized response to morphine compared with those receiving morphine for the first time. These findings are virtually identical to our previous findings in female rats treated with amphetamine. Among males, only intact animals showed a progressive increase in morphine-induced activity and only in the second hour of testing, but, overall, there was no significant effect of either group or drug during the pre-exposure phase. On the test for sensitization, as seen in females, those males that had been exposed to morphine previously showed a sensitized responses to morphine. There were, however, no differences in activity levels between the groups of males. We conclude that although gonadal hormones, and in particular estradiol, may modify the magnitude of the response to amphetamine and morphine, they appear not to be involved in those neurochemical and neuronal changes that occur during and following repeated drug exposures, and that underlie the enhanced sensitivity to the stimulant effects of a drug seen when such animals are compared with animals receiving the drug for the first time.

Animals↗

The effectiveness of light on the circadian clock is linked to its emotional value.

Studies carried out within the primary visual system have shown that neural responses to light stimuli transmitted via the retinogeniculate pathway are significantly altered when these stimuli are made aversive through conditioning. The effect of such aversive conditioning on neural responses to light transmitted within the circadian visual system has not been investigated. In mammals, the principal projection of the circadian visual system, the retinohypothalamic tract, is functionally and anatomically distinct from the primary visual pathway allowing for direct transmission of light from the retina to the suprachiasmatic nucleus of the hypothalamus, the circadian clock. Light transmitted within this pathway is essential for entrainment of circadian rhythms providing the critical stimulus for resetting the circadian clock. We asked whether the response of neural elements within the suprachiasmatic nucleus to a resetting light stimulus would be altered if that stimulus had acquired aversive properties through conditioning. To study this we assessed the effect of a light stimulus made aversive through pairings with footshock on a cellular correlate of clock resetting, the expression of the transcription factor Fos in neurons of the suprachiasmatic nucleus. We show that Fos expression in the suprachiasmatic nucleus in response to light previously paired with footshock is significantly suppressed. This finding provides the first evidence that the effectiveness of a light as a resetting stimulus can be modulated by its conditioned aversive properties.

Animals↗

Conditioned and unconditioned aversive stimuli enhance light-induced fos expression in the primary visual cortex.

Studies in rats indicate that photic responses within the dorsal lateral geniculate nucleus can be enhanced in response to stimuli known to induce negative emotional arousal. Little is known, however, about the effect of such stimuli on photic responses within primary visual cortex, the principal projection area of the dorsal lateral geniculate. Here, we examined the effect of unconditioned and conditioned aversive stimuli on photic responses within the primary visual cortex in rats using expression of the transcription factor Fos as a functional marker of neuronal activation. In previous studies carried out within the circadian visual system, we found that photic induction of Fos within the principal target area of the circadian visual pathway, the suprachiasmatic nucleus of the hypothalamus, was attenuated when the light stimulus was given concurrently with an aversive footshock or was made an aversive conditioned stimulus through previous pairings with footshock. In addition, we found that photic stimulation of Fos expression in the suprachiasmatic nucleus was attenuated in a context made aversive through previous pairings with footshock. We now report that in these same animals, unlike what was seen within the suprachiasmatic nucleus, Fos expression in the primary visual cortex is significantly elevated. These findings support the view that emotional arousal can enhance the response of cells in the visual cortex to photic input, and point to the differential effect of aversive emotional events on photic responses within pathways underlying visual perception and those involved in circadian regulation.

Animals↗

Olfactory stimulation enhances light-induced phase shifts in free-running activity rhythms and Fos expression in the suprachiasmatic nucleus.

There is evidence to suggest that the olfactory and circadian systems are linked, functionally, and that olfactory stimuli can modulate circadian rhythms in mammals. Furthermore, olfactory bulb removal can alter free-running rhythms in animals housed in constant darkness and can attenuate the effect of social stimuli on photic entrainment of circadian rhythms. The mechanisms through which olfactory stimuli influence circadian rhythms are not known. One possibility is that olfactory stimuli influence circadian rhythms by modulating the activity of the circadian clock located in the hypothalamic suprachiasmatic nucleus. To study this, we assessed the effect of olfactory stimulation on free-running rhythms and on photic resetting of the circadian clock in rats using phase shifts in wheel-running rhythms and expression of the transcription factor Fos in the suprachiasmatic nucleus. We found that brief exposure to an olfactory stimulus, cedar wood essence, in the subjective day or subjective night had no effect on either free-running rhythms or Fos expression in the suprachiasmatic nucleus, but that when presented in combination with light, the odor dramatically enhanced light-induced phase shifts and Fos expression in the suprachiasmatic nucleus. Olfactory stimulation alone induced Fos expression in several structures that innervate the suprachiasmatic nucleus, pointing to ways by which stimulus information transmitted in the olfactory pathways could gain access to the suprachiasmatic nucleus to modulate photic resetting. These findings, showing that clock resetting by light can be facilitated by olfactory stimulation, point to a mechanism by which olfactory cues can modulate entrainment of circadian rhythms.

Animals↗

Phenotypic changes in the lipopolysaccharide of Pseudomonas aeruginosa and Escherichia coli grown in milk-based enteral nutrition solutions.

Previous studies have shown enteral nutritional solutions (ENS) contaminated with large numbers of microorganisms from the environment or gastrointestinal (GI) tract of patients have caused respiratory infections, acute and chronic enteritis, and septicemia. The introduction of "closed" enteral feeding systems has been used to prevent contaminating organisms from entering enteral feeding systems in large numbers. However, there is some discussion as to whether this has been an effective measure in reducing ENS-related infections because there is anecdotal evidence to suggest that disease processes resulting from enteral feeding are still commonplace in the hospital and home. This is because there is very little information about the growth of microorganisms in ENS and whether growth in ENS may affect the virulence and pathogenicity of microorganisms. This study shows that Escherichia coli and Pseudomonas aeruginosa may grow at 25 degrees C from either high or low initial numbers to up to 9.2 log colony-forming units per mL in a range of milk-based ENS. However, these organisms did not grow in the fruit-based ENS. The effect on the lipopolysaccharide (LPS) of culturing E. coli and P. aeruginosa in milk-based ENS as opposed to standard laboratory media was examined using polyacrylamide gel electrophoresis. We found that there were significant qualitative changes in the phenotype of O-polysaccharide side chains of the LPS from these organisms. O-polysaccharide is known to mediate in the complement, antibiotic and bile resistance, and affect adherence. Therefore, changes in the virulence and pathogenicity of these microorganisms when cultured in ENS may be indicated. Thus, the study provides further evidence for reevaluating the microbiologic and immunologic effects of enteral feeding, especially on the microbial flora of the GI tract.

Animals↗

The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy.

PURPOSE: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy. METHODS: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed. RESULTS: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period. CONCLUSION: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.

Adolescent↗

Observations on the effect of abolishing analgesic abuse and reducing smoking on cancers of the kidney and bladder in New South Wales, Australia, 1972-1995.

OBJECTIVES: We have assessed the effect on the rates of cancers of the kidney and bladder of measures undertaken by the government in 1979-1983 to limit smoking and analgesic abuse in New South Wales (NSW). Sale of phenacetin-containing analgesics, previously available without restriction and regularly taken by 11-13% of women and 4-9% of men in NSW, was prohibited from 1979. The prevalence of current smokers among adult Australian men had fallen from 72% in 1945 to 43% in 1980 and to 28% in 1992. In women the corresponding figures were 26%, 31% and 24%. METHODS: Incidence and mortality data from the New South Wales Central Cancer Registry for the period 1972 to 1995 were analyzed, by sex and age, for trends over time. Relative survival was calculated for cases diagnosed in the period 1980-94 and followed until the end of 1996. RESULTS: Significant trends evident from these data were: throughout the period of review a rising incidence of, and to a lesser extent mortality from, renal parenchymal cancer for which relative survival has steadily improved; falling mortality from bladder cancer throughout the period of review, but more rapid after 1985; a reversal of the earlier increasing incidence of, and mortality from, cancer of the renal pelvis; and relative survival for bladder and renal pelvic cancers which was worse in women than men. Changes in registration practice in 1985 and 1993 introduced artifacts into the trends in incidence of bladder cancer. CONCLUSIONS: Improvements in the trends of incidence and mortality of cancers of the renal pelvis and bladder in the mid-1980s are interpreted, in the light of registration and clinical practice, to indicate a beneficial effect of regulations which virtually abolished analgesic abuse and, less certainly, a contribution from measures restricting smoking, in New South Wales. However, renal parenchymal cancer continues to increase, although there has been some apparent benefit of earlier detection.

Adult↗

Follow-up of breast cancer in primary care vs specialist care: results of an economic evaluation.

A randomized controlled trial (RCT) comparing primary-care-centred follow-up of breast cancer patients with the current standard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence, and no increase in anxiety or deterioration in health-related quality of life. An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT Because the RCT found no difference in the primary clinical outcomes, a cost minimization analysis was conducted. Process measures of the quality of care such as frequency and length of visits were superior in primary care. Costs to patients and to the health service were lower in primary care. There was no difference in total costs of diagnostic tests, with particular tests being performed more frequently in primary care than in specialist care. Data are provided on the average frequency and length of visits, and frequency of diagnostic testing for breast cancer patients during the follow-up period.

Breast Neoplasms↗