bluuebunny/crossref_metadata_2025 huggingface dataset:
CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions
Authors: Plumb J , Armstrong M A , Duddy M , Mirakhur M , McQuaid S
Published: March 2003

Multiple sclerosis (MS) has a wide spectrum of clinical courses, character ized by multifocal central nervous system (C NS) damage, postulated to be mediated by C NS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to C D1a (immature DC) and C D83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry. No C D1a-positive cells were detected in the MS or control C NS tissue blocks investigated. C D83-po sitive cells were not detected in tissues from any of the control cases or in the majority of perivascular cuffs in the MS tissue sections. However, in eight of the MS tissue blocks with evidence of recent demyelination, and in one block each from chronic plaque and NAWM, small numbers of distinct C D83-positive cells were present within occasional perivascular cuffs. In one area only of MS NAWM were C D83-po sitive cells detected in the tissue parenchyma, in an area of intense immunological activity. DC in MS tissue may originate in the peripheral circulation as monocytes or immature DC and migrate to areas of plaque in response to signals received from C NS-produced chemokines.
The utility of computerized neuropsychological assessment of cognitive dysfunction in patients with relapsing-remitting multiple sclerosis
Authors: Wilken J A , Kane R , Sullivan C L , Wallin M , Usiskin J B , Quig M E , Simsarian J , Saunders C , Crayton H , Mandler R , Kerr D , Reeves D , Fuchs K , Manning C , Keller M
Published: March 2003

Traditional paper-and-pencil neuropsychological batteries used to document cognitive deficits in multiple sclerosis (MS) patients lack timing precision. This makes it difficult to accurately measure psychomotor slowing, a central cognitive symptom of MS. A dditionally, traditional batteries lack multiple alternate forms necessary to control for practice effects when assessing cognition over time. Finally, such batteries are lengthy and expensive. C omputerized neuropsychological batteries address many of these shortcomings. They measure response time more precisely, require less administration time, include alternate forms, and are ideal for rapid screening/triage. Although there are normative data on the reliability and validity of computerized measures, there have been no controlled validation studies with MS patients. The current study was designed to validate a computerized neuropsychological batter y (ANAM) for use with relapsing-remitting (RR) MS patients. Prior to initiation of interferon-b-1a (Avonex) treatment, subjects participated in a neuropsychological evaluation consisting of traditional and computerized measures. Moderate-to -high correlations were found between computerized and traditional measures. C omputerized tests accurately predicted performance on key traditional tests. The batter y was also concordant with traditional measures in identifying RR MS patients with and without neurocognitive impairment. Findings are discussed with respect to increased accuracy and accessibility of neuropsychological evaluations for MS patients.
Genome-wide linkage screen of a consanguineous multiple sclerosis kinship
Authors: Modin H , Masterman T , Thorlacius T , Stefánsson M , Jónasdóttir A , Stefánsson K , Hillert J , Gulcher J
Published: March 2003

Multiple sclerosis (MS), like A lzheimer’s disease (A D) and Parkinson’s disease (PD), is a common neurological disorder thought to be caused by the interaction of several genes with unknown environmental factors. In both A D and PD the identification of disease forms inherited in a classic Mendelian fashion has helped investigators elucidate pathogenetic mechanisms. In this study a whole-genome screen, with an average of 608 successful genotypes per person, was performed on nine members of a consanguineous family: the index case, three of her siblings and her daughter, all of whom have been diagnosed with definite MS; as well as the parents of the index case (first cousins), one of her five healthy siblings and her husband (who is also her first cousin). Nonparametric linkage analysis was performed on genotyping data. Based on the presence of consanguinity, the a priori hypothesis was that the disease is transmitted in an autosomal recessive fashion in the pedigree. Linkage analysis revealed a suggestive logarithm of odds (LO D) score of 2.29 on the long arm of chromosome 9. Four of five affected family members were identically homozygous for a haplotype under this peak, spanning approximately 43 cM, while the fifth affected subject and all unaffected family members were hetero zygous for the haplotype.
Predicting multiple sclerosis at optic neuritis onset
Authors: Jin Y P , de Pedro-Cuesta J , Huang Y H , Söderström M
Published: March 2003

Using multivariate analyses, individual risk of clinically definite multiple sclerosis (C DMS) after monosymptomatic optic neuritis (MO N) was quantified in a prospective study with clinical MO N onset during 1990 -95 in Stockholm, Sweden. During a mean follow-up time of 3.8 years, the presence of MS-like brain magnetic resonance imaging (MRI) lesions and oligoclonal immunoglobulin (Ig) G bands in cerebrospinal fluid (CSF) were strong prognostic markers of C DMS, with relative hazard ratios of 4.68 {95% confidence interval (CI) 2.21 -9.91} and 5.39 (95% C I 1.56 -18.61), respectively. Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95% C I 1.02 -3.04) and 2.21 (95% C I 1.13 -3.98), respectively. Based on the above two strong predicto rs, individual probability of C DMS development after MO N was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years. The highest probability, 0.66 (95% C I 0.48 -0.80), was obtained for individuals presenting with three or more brain MRI lesions and oligoclonal bands in the C SF, and the lowest, 0.09 (95% C I 0.02 -0.32), for those not presenting with these traits. Medium values, 0.29 (95% C I 0.13 -0.53) and 0.32 (95% C I 0.07 -0.73), were obtained for individuals discordant for the presence of brain MRI lesions and oligoclonal bands in the C SF. These predictions were validated in an external one-quarter sample.
Comprehension of affective prosody in multiple sclerosis
Authors: Beatty William W , Orbelo Diana M , Sorocco Kristen H , Ross Elliott D
Published: March 2003

Deficits in cognition have been repeatedly documented in patients with multiple sclerosis (MS), but their ability to comprehend emotional information has received little study. Forty-seven patients with MS and 19 demographic controls received the comprehension portion of the A prosodia Battery, which is known to be sensitive to the impairments of patients with strokes and other neurological conditions. Patients also received tests of hearing, verbal comprehension and naming, a short cognitive battery, and the Beck Depression Inventory. Patients with MS were impaired in identifying emotional states from prosodic cues. The magnitude of the deficits was greatest for patients with severe physical disability and under test conditions of limited prosodic information.

Correlational analyses suggested that the patients’ difficulties in comprehending affective prosodic information were not secondary to hearing loss, aphasic deficits, cognitive impairment, or depression. For some patients with MS, deficits in comprehending emotional information may contribute to their difficulties in maintaining effective social interactions.
Longitudinal study of chemokine receptor expression on peripheral lymphocytes in multiple sclerosis: CXCR3 upregulation is associated with relapse
Authors: Mahad D J , Lawry J , Howell S JL , Woodroofe M N
Published: March 2003

The interaction between chemokines and their recepto rs leads to selective recruitment of cells to foci of inflammation. C ross-sectional studies have reported significantly different expression of chemokine recepto rs C XC R3, C C R5 and C C R2 on peripheral blood lymphocytes in multiple sclerosis (MS) compared with controls. C ells expressing these receptors are likely to play a pathogenic role as suggested by studies of experimental autoimmune encephalo myelitis. A lso, immunogenetic studies of nonfunctional C C R5 recepto rs in MS patients, due to 32d deletion, demonstrated a delay in time to next relapse. The aims of this study were to detect any changes in the serial expression of chemokine recepto rs C C R2, C C R3, C C R5 and C XCR3 on peripheral blood C D4 lymphocytes from patients with MS and to correlate the changes with relapses. Upregulation of C XCR3 expression on peripheral blood C D4 lymphocytes was associated with all relapses and C C R5 expression was significantly affected with all relapses. C linical recovery, with or without intravenous methylprednisolone treatment, coincided with the return of C XC R3 towards baseline in all but one case. Fluctuation in the expression of C XC R3 and C C R5 was also significantly greater in clinically stable patients with MS compared with controls, which may be due to subclinical disease activity. These findings provide further support for the view that C XC R3 and C C R5 antagonists could have a therapeutic value in MS.
Pharmacologic treatment for intermittent claudication
Authors: Dean Steven M
Published: April 2003

In contradistinction to chronic critical limb ischemia, the peripheral arterial disease patient with intermittent claudication is at relatively low risk for limb loss. As a result, initial claudication management should employ non-interventional therapies rather than immediate catheter-based or surgical revascularization. Although exercise therapy is the most efficacious conservative treatment for claudication, supervised exercise programs are not widely available at present. Consequently, a pharmacologic agent can be utilized to lessen the symptoms and improve the function of the claudicant. This manuscript provides a comprehensive review of the various pharmacotherapies that have been investigated for improving walking distance in the setting of intermittent claudication. Cilostazol, a phosphodiesterase III inhibitor, appears to provide the greatest benefit, significantly improving not only walking distance but quality of life as well. Early trials indicate that propionyl-l-carnitine, oral prostaglandins, l-arginine, and therapeutic angiogenesis may eventually yield significant benefit in lessening the symptoms of intermittent claudication.
Prothrombotic determinants of coronary atherothrombosis
Authors: Ruberg Frederick L , Loscalzo Joseph
Published: April 2003

An acute coronary syndrome (ACS) is the clinical manifestation of a thrombotic event occurring within a coronary artery narrowed by atherosclerosis. This atherothrombotic event is thought to occur following destabilizing changes within the atherosclerotic plaque, rendering it a surface on which thrombus can develop. The development and progression of this thrombus are determined by deleterious perturbations in the hemostatic equilibrium within the local environment of the plaque that favor thrombosis. Major risk factors for the development of atherosclerotic disease have been clearly established and are targets of aggressive modification in an effort to impede the development or slow the progression of disease. While conferring an increased risk for plaque development, these and other risk factors also establish a prothrombotic milieu within the microenvironment of the atherosclerotic plaque that favors thrombosis. This review seeks to address these traditional and emerging risk factors from the context of their pathologic effects on local hemostatic balance. Aggressive risk factor modification not only reduces atherosclerotic disease development and progression, but also ameliorates the prothrombotic state, and ultimately serves to reduce atherothrombotic events.
Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing clinically important venous thromboembolism in medical patients: the Prospective Evaluation of Dalteparin efficacy for Prevention of Venous Thromboembolism in Immobilized Patients Trial (the PREVENT study)
Authors:   The PREVENT Investigator Group
Published: April 2003

The utility of low-molecular-weight heparin (LMWH) in the prophylaxis of venous thromboembolic disease has been examined using the surrogate endpoint of venographically identified thrombi. The largest portion of these thrombi were asymptomatic calf-vein thrombi. The clinical relevance of this observation is a matter of debate. The present study is designed to evaluate the impact of an LMWH on clinically important endpoints.

The current study is a randomized, prospective, double-blinded, multicenter, multinational, controlled clinical trial comparing dalteparin with placebo in moderately high-risk hospitalized medical patients. A total of 3300 patients will be randomized to receive either 5000 IU per day of dalteparin or placebo for 14 days. Patients will undergo appropriate evaluation for any symptomatic episodes and all patients will undergo a bilateral compression ultrasound (CUS) on day 21 to search for asymptomatic proximal thrombi.

The primary endpoint is the combination of objectively confirmed symptomatic deep vein thrombi (DVT), fatal or non-fatal pulmonary emboli, all proximal DVT, and sudden death.

This study will be the first study to examine clinically important endpoints in evaluating the effect of a LMWH in hospitalized medical patients. This study also is the first study to use CUS rather than venography in concordance with contemporary medical practice. This trial is thus designed to address this important question in a clinically relevant manner.
Acute aortic syndrome: a case presentation and review of the literature
Authors: Lissin Lynette Wroblewski , Vagelos Randall
Published: April 2003

Aortic disease can present as an acute chest pain syndrome. Although aortic dissection is the most common etiology, other processes such as intramural hematoma (IMH) and penetrating atherosclerotic ulcers are being increasingly recognized. They can all be accurately identified by computed tomography (CT) imaging or transesophageal echocardiography. The overlap between these processes regarding definition and mechanism is controversial. Treatment for all three conditions has thus far been dictated by location, wherein ascending or arch involvement (Stanford type A) necessitates surgery and descending disease (type B) is treated medically. Small studies suggest that subgroups of type A IMH may be treated medically with good outcomes.
Antiphospholipid antibodies in thromboangiitis obliterans
Authors: Maslowski Leszek , McBane Robert , Alexewicz Pawel , Wysokinski Waldemar E
Published: April 2003

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear.

aCLa were measured by double ELISA in patients with TAO (n=47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n=48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p=0.01) or healthy individuals (2%; p,0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p=0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals.

TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.
Undertreatment of dyslipidemia in peripheral arterial disease and other high-risk populations: an opportunity for cardiovascular disease reduction
Authors: Hirsch Alan T , Gotto Antonio M
Published: April 2003

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early Identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8-10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors(e.g., smoking and diabetes). efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle-brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as ‘coronary heart disease risk equivalent’ syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation.
Mesenteric arterial ischaemia: diagnosis and therapeutic options
Authors: Cleveland TJ , Nawaz S , Gaines PA
Published: April 2003

Ischaemia of the bowel may arise from a number of causes affecting the arterial and venous compartments of the vascular tree. This article addresses the causes and consequences of arterial obstruction, which may compromise the supply of oxygenated blood to the bowel. These events may occur as an acute phenomenon, or they may present in a chronic fashion. The therapeutic options available to treat this condition are largely dependent on the mode of presentation and the amount of time that is available before irreversible damage occurs to the bowel integrity. In the acute phase, the viability of the bowel is in doubt, and this necessitates an open operative approach to assess the amount of bowel infarction which has already occurred. A variety of operative procedures are then available to limit this bowel loss and to secure the viability of the remaining bowel. In the more chronic phase there are alternative, less invasive procedures that may be appropriate for the patient, who may have suffered a prolonged period of undernourishment and dehydration. In such cases the immediate bowel viability is not in doubt, but the medium/long-term survival is compromised. Treatment options appropriate to each clinical scenario are discussed, along with the major technical issues associated with these treatments. A team approach to the most appropriate management plan is stressed, and the published outcomes reviewed.
The use of Ginkgo biloba in Raynaud’s disease: a double-blind placebo-controlled trial
Authors: Muir Andrew H , Robb Rosalind , McLaren Margaret , Daly Fergus , Belch Jill JF
Published: April 2003

Raynaud’s phenomenon (RP) is a common and painful condition characterized by episodic digital ischaemia produced by emotion and cold. Treatment of RP is notoriously difficult because of the high incidence of side effects. The aim of our study was to investigate the clinical efficacy of a standardized Ginkgo biloba extract (Seredrin) in the treatment of RP in patients with no apparent, associated condition such as systemic sclerosis.

A two-week assessment period was done during which patients were asked to record frequency, severity and duration of attacks in diaries. Subjects were then randomized independently of the study centre to receive either active or placebo treatment for 10 weeks, during which time the same data were recorded in their diaries. Patients were seen after two and four weeks of treatment and at the end of the 10-week treatment phase. Blood samples pre- and post-treatment were taken for haemorrheology.

Only in the number of attacks per day was there a significant effect of treatment over placebo. The number of attacks per week prior to treatment with Seredrin was 13.2 6 16.5 reducing to 5.8 6 8.3, a reduction of 56%, whereas placebo reduced the number by only 27% (p < 0.00001). There were no significant differences in haemorrheology between the two groups.

Ginkgo biloba phytosome may be effective in reducing the number of Raynaud’s attacks per week in patients suffering from Raynaud’s disease.
Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure
Authors: Gray Bruce H , Olin Jeffrey W , Childs Mary Beth , Sullivan Timothy M , Bacharach J Michael
Published: April 2003

Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of flash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and flash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21).

Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50- 85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 6 32/23 mmHg to 148/72 6 24/14 mmHg (p < 0.001). Mean number of blood pressure medications decreased from 3 6 1 to 2.5 6 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 6 1.61 to 2.65 6 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 6 1.4 and poststenting was 0.3 6 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 6 0.9 prestenting to 1.6 6 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the first year after renal artery stenting.

Renal artery stenting decreased the frequency of congestive heart failure, flash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or flash pulmonary edema.
Vascular viewpoint
Authors: Hackam Daniel , Anand Sonia S
Published: April 2003

Question: Does oral acetylcysteine prevent acute contrast nephropathy in patients with moderate renal impairment who undergo elective coronary angiography?

Population: Patients with moderate stable renal insufficiency (creatinine clearance,60 ml/min or serum creatinine .1.2 mg/dl [106 mmol/l]) who were scheduled to undergo elective coronary angiography with or without intervention.

Design and methods: Randomized placebo-controlled trial. A total of 200 patients were randomized to either oral acetylcysteine 600 mg BID (n = 102) or matching placebo (n = 98). Treatment was given for a total of four doses, starting the day before angiography and continuing on the day of the procedure. All patients received intravenous normal saline for 12 hours before and 6 hours after contrast exposure, and low osmolality contrast agents. Primary outcome was the occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast exposure. Coprimary outcomes were a change in creatinine clearance and serum creatinine level. Secondary outcomes were major adverse cardiac events, need for dialysis, and length of hospitalization. Patients, caregivers, and outcome assessors were blinded to group assignment. Analysis was by intention-to-treat.

Results: Within 48 hours after contrast administration 12/98 (12%) control patients and 4/102 (4%) acetylcysteine patients developed a more than 25% increase in serum creatinine level. Relative risk = 0.32 (95% CI: 0.10--0.96; p = 0.03). Serum creatinine was lower in the acetylcysteine group than in the control group during the first 48 hours after angiography (1.22 mg/dl [108 mmol/l] vs 1.38 mg/dl [122.9 mmol/l]; p = 0.006), but this difference was no longer significant at seven days. Creatinine clearance increased significantly more in the acetylcysteine group than in the placebo group at day two [+30% vs +5%; p < 0.001] and at day seven [+23% vs +15%; p = 0.045]. The average length of stay was half a day shorter in the group receiving acetylcysteine(p = 0.02). No patients in either group required dialysis. There were no treatment-related adverse events.

Conclusions: Acetylcysteine safely and effectively reduces the incidence of contrast-induced nephropathy in patients with moderate renal insufficiency undergoing coronary angiography.
Re-examining thought insertion
Authors: Mullins Simon , Spence Sean A.
Published: April 2003

Background

Thought insertion is commonly regarded as diagnostic of schizophrenia. Little is known of its aetiology or pathophysiology.

Aims

To examine the definition and application of thought insertion in psychiatric and allied literatures.

Method

A semi-structured literature review and conceptual analysis.

Results

When ‘narrowly’ defined, thought insertion is reliably identified but not specific to schizophrenia. There is a range of related phenomena (‘alienated’, ‘influenced’, ‘made’ and ‘passivity’ thinking), less consistently defined but also not specific to schizophrenia. Whether thought insertion is solely an abnormal belief (or may also be an experience) is open to question. Nevertheless, the symptom has been used to explain schizophrenia, predict dangerousness and advance theories of ‘normal’ agency. Most applications have been subject to critique.

Conclusions

Despite its widespread occurrence and diagnostic application, thought insertion is an ill-understood and under researched symptom of psychosis. Its pathophysiology remains obscure.
Providing treatment to prisoners with mental disorders: development of a policy
Authors: Earthrowl Mark , O'Grady John , Birmingham Luke
Published: March 2003

Background

Mental disorder is more prevalent among people in prison than in the general population. Prisoners who require transfer to psychiatric hospitals for treatment face long delays. Doctors working in prisons regularly face ethical and legal dilemmas posed by prisoners with mental illness.

Aims

To develop a policy for providing treatment under the common law to prisoners with mental disorders who lack treatment decision-making capacity while arrangements are made to transfer them to hospital.

Method

The policy was developed through literature review and consultation with the Faculty of Law at Southampton University and health care staff at Winchester prison in the UK.

Results

The policy provides guidelines for establishing decision-making capacity standards for documentation, and guidelines for implementation based on the Mental Health Act Code of Practice, other best-practice guidelines and case law.

Conclusions

It can be argued that case law allows more-extensive treatment to be provided in the best interests of the incompetent prisoner, beyond emergency situations. The policy has ethical implications and its use should be carefully monitored.
Tayside–Fife clinical trial of cognitive–behavioural therapy for medication-resistant psychotic symptoms
Authors: Durham Robert C. , Guthrie Moyra , Morton R. Victor , Reid David A. , Treliving Linda R. , Fowler David , MacDonald Ranald R.
Published: April 2003

Background

Evidence for the efficacy of cognitive–behavioural therapy for schizophrenia is promising but evidence for clinical effectiveness is limited.

Aims

To test the effectiveness of cognitive–behavioural therapy delivered by clinical nurse specialists in routine practice.

Method

Of 274 referrals, 66 were allocated randomly to 9 months of treatment as usual (TAU), cognitive–behavioural therapy plus TAU (CBT) or supportive psychotherapy plus TAU (SPT) and followed up for 3 months.

Results

Treatment effects were modest but the CBT condition gave significantly greater improvement in overall symptom severity than the SPT or TAU conditions combined (F (1,53)=4.14; P=0.05). Both the CBT and SPT conditions combined gave significantly greater improvement in severity of delusions than did the TAU condition (F (1,53)=4.83; P=0.03). Clinically significant improvements were achieved by 7/21 in the CBT condition (33%), 3/19 in the SPT condition (16%) and 2/17 in the TAU condition (12%).

Conclusions

Cognitive–behavioural therapy delivered by clinical nurse specialists is a helpful adjunct to routine care for some people with chronic psychosis.
Exposure therapy and sertraline in social phobia: 1-year follow-up of a randomised controlled trial
Authors: Haug Tone Tangen , Blomhoff Svein , Hellstrøm Kerstin , Holme Ingar , Humble Mats , Madsbu Hans Petter , Wold Jan Egil
Published: April 2003

Background

Maintenance of treatment effect is important for the choice of treatment for social phobia.

Aims

To examine the effect of exposure therapy and sertraline 28 weeks after cessation of medical treatment.

Method

In this study 375 patients with social phobia were randomised to treatment with sertraline or placebo for 24 weeks, with or without the addition of exposure therapy Fifty-two weeks after inclusion, 328 patients were evaluated by the same psychometric tests as at baseline and the end of treatment (24 weeks).

Results

The exposure therapy group and the placebo group had a further improvement in scores on social phobia during follow-up: mean change in the Clinical Global Impression – Social Phobia overall severity score was 0.45 (95% CI 016–0.65, P < 0.01) for the exposure group, and 0.25 (95% CI 0.00–0.48, P < 0.05) for the placebo group. At week 52 the sertraline plus exposure group and the sertraline-alone group had a significant deterioration on the 36-item Short Form Health Survey compared with exposure alone.

Conclusions

Exposure therapy alone yielded a further improvement during follow-up, whereas exposure therapy combined with sertraline and sertraline alone showed a tendency towards deterioration after the completion of treatment.
Risk factors for the development of lithium-induced polyuria
Authors: Movig K. L. L. , Baumgarten R. , Leufkens H. G. M. , Van Laarhoven J. H. M. , Egberts A. C. G.
Published: April 2003

Background

Polyuria is common in patients with bipolar disorder treated with lithium. However, the risk factors for polyuria in these patients have not been established.

Aims

To estimate the prevalence of polyuria associated with the use of lithium and to identify additional risk factors.

Method

A 4-month prospective follow-up study in an out-patient lithium clinic. The 75 participants were asked to provide 24-h urine samples; polyuria was defined as a urine volume greater than 3 litres per 24 h. Risk factors examined included demographic variables, medications and medical comorbidities.

Results

The prevalence of polyuria among lithium users was 37%. Concomitant use of serotonergic antidepressants was strongly associated with polyuria (odds ratio 4.25, 95% CI 1.15–15.68) compared with patients not using these agents.

Conclusions

Our data confirm the high prevalence of lithium-induced polyuria. Physicians should be aware that concurrent use of serotonergic antidepressants and lithium significantly enhances the risk of its occurrence. Although limited polyuria is not harmful, it may be troublesome for the patient. In many cases cessation of lithium therapy is not an option because of difficulty in controlling the manic or depressive symptoms.
Adolescent precursors of cannabis dependence: findings from the Victorian Adolescent Health Cohort Study
Authors: Coffey Carolyn , Carlin John B. , Lynskey Michael , Li Ning , Patton George C.
Published: April 2003

Background

Dependence increases the likelihood of adverse consequences of cannabis use, but its aetiology is poorly understood.

Aims

To examine adolescent precursors of young-adult cannabis dependence.

Method

Putative risk factors were measured in a representative sample (n=2032) of secondary students in the State of Victoria, Australia, six times between 1992 and 1995. Cannabis dependence was assessed in 1998, at age 20–21 years.

Results

Of 1601 young adults, 115 met criteria for cannabis dependence. Male gender (OR=2.6, P < 0.01), regular cannabis use (weekly: OR=4.9; daily: OR=4.6, P=0.02), persistent antisocial behaviour (linear effect P=0.03) and persistent cigarette smoking (linear effect P=0.02) independently predicted cannabis dependence. Neither smoking severity (P=0.83) nor persistent psychiatric morbidity (linear effect P=0.26) independently predicted dependence. Regular cannabis use increased risk only in the absence of persistent problematic alcohol use.

Conclusions

Weekly cannabis use marks a threshold for increased risk of later dependence, with selection of cannabis in preference to alcohol possibly indicating an early addiction process.
Management of mental illness by the British Army
Authors: Neal Leigh A. , Kiernan Matthew , Hill David , Mcmanus Frank , Turner Mark A.
Published: March 2003

Background

The Ministry of Defence has its own hospital for soldiers requiring admission for mental health problems.

Aims

To assess the efficiency of the army psychiatric hospital at restoring patients to full active duty. To assess whether a new military training and rehabilitation unit (MTRU) that emphasises military-skills training, improves outcome.

Method

A 2-year, inception-cohort outcome study of hospital in-patients. A 12-month, case-matched, ‘before and after’ outcome study compared MTRU patients with hospital in-patients.

Results

I (hospital in-patients, n=309): at 2-year follow-up 67 (22%) were fully fit for active duty Military psychiatrists' success rate at predicting recovery to active duty was 27%. 2: the odds of a soldier in the MTRU cohort (n=35) returning to active duty were 14 times greater than for the hospital cohort (n=35). The odds of remaining in the army while unfit for active duty were 20 times less for the MTRU than for the hospital cohort.

Conclusions

The army hospital is inefficient at rehabilitation to active duty. The MTRU significantly increased the odds of returning to active duty and reduced the odds of remaining in the army while still unfit. These findings may be applicable to the emergency services.
Reducing psychiatric stigma and discrimination: evaluation of educational interventions in UK secondary schools
Authors: Pinfold Vanessa , Toulmin Hilary , Thornicroft Graham , Huxley Peter , Farmer Paul , Graham Tanya
Published: April 2003

Background

The persistent and disabling nature of psychiatric stigma has led to the establishment of global programmes to challenge the negative stereotypes and discriminatory responses that generate social disability but these initiatives are rarely evaluated.

Aims

To assess the effectiveness of an intervention with young people aimed at increasing mental health literacy and challenging negative stereotypes associated with severe mental illness.

Method

A total of 472 secondary school students attended two mental health awareness workshops and completed pre- and post-questionnaires detailing knowledge, attitudes and behavioural intentions.

Results

Young people use an extensive vocabulary of 270 different words and phrases to describe people with mental health problems: most were derogatory terms. Mean positive attitude scores rose significantly from 1.2 at baseline to 2.8 at 1-week follow-up and 2.3 at a 6-month follow-up. Changes were most marked for female students and those reporting personal contact with people with mental illness.

Conclusions

Short educational workshops can produce positive changes in participants' reported attitudes towards people with mental health problems.
Stereological quantitation in cerebella from people with schizophrenia
Authors: Andersen Birgitte Bo , Pakkenberg Bente
Published: March 2003

Background

Behavioural and anatomical studies in schizophrenia have pointed to cerebellar involvement.

Aims

To provide stereological estimations of volumes and cell number in the cerebella of people with schizophrenia and a control group using post-mortem material.

Method

Stereological methods were applied to cerebella taken from eight male patients with a DSM–III diagnosis of chronic schizophrenia with no neurological disorder (mean age 57.5 years) and ten male controls (mean age 56.2 years). The Cavalieri principle was used to provide estimates of volumes, the optical disector method to obtain estimates of the numerical density of Purkinje and granule cells, and a combination of the two to obtain estimates of total cell numbers in the cerebellum. The rotator method was applied to obtain estimates of mean Purkinje cell volume.

Results

No global structural difference in major volumes, cell numbers or Purkinje cell volume was found between the groups.

Conclusions

The most frequently reported pathological finding in the cerebellum in schizophrenia is vermal atrophy, which was not found in this small group of heavily affected patients.
Money for mental health care in 2003/4
Authors: Glover Gyles R.
Published: March 2003

On Christmas Eve 2002, the Department of Health published the financial allocations to Primary Care Trusts (PCTs) for 2003/4. As usual, this was accompanied by a detailed ‘exposition book’, setting out how the distribution of the available £45.3 bn was decided (Department of Health Finance and Investment Directorate, 2002). Three years ago, I wrote a short article showing how a close reading of this publication could be used to identify notional mental health budgets in these allocations (Glover, 1999). Bindman et al (2000) demonstrated that many health authorities, particularly those that service more deprived areas, spend substantially less on mental health care. As this is the first time financial allocations have been made directly to PCTs, it is helpful to repeat that calculation for the new organisations.
Early Autologous Stem-Cell Transplantation Versus Conventional Chemotherapy as Front-Line Therapy in High-Risk, Aggressive Non-Hodgkin’s Lymphoma: An Italian Multicenter Randomized Trial
Authors: Martelli Maurizio , Gherlinzoni Filippo , De Renzo Amalia , Zinzani Pier Luigi , De Vivo Antonio , Cantonetti Maria , Falini Brunangelo , Storti Sergio , Meloni Giovanna , Rizzo Manuela , Molinari Anna Lia , Lauria Francesco , Moretti Luciano , Lauta Vito Michele , Mazza Patrizio , Guardigni Luciano , Pescarmona E. , Pileri S.A. , Mandelli Franco , Tura Sante
Published: March 2003

Purpose: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin’s lymphoma (NHL).

Patients and Methods: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.

Results: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P = .95), 5-year progression-free survival was 49% and 61% (P = .21), and 5-year relapse-free survival was 65% and 77% (P = .22), respectively.

Conclusion: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.
Phase III Study of Interferon Alfa-NL as Adjuvant Treatment for Resectable Renal Cell Carcinoma: An Eastern Cooperative Oncology Group/Intergroup Trial
Authors: Messing Edward M. , Manola Judith , Wilding George , Propert Kathleen , Fleischmann Jonathan , Crawford E. David , Pontes J. Edson , Hahn Richard , Trump Donald
Published: March 2003

Purpose: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma.

Patients and Methods: A total of 283 eligible patients with pT3–4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate.

Results: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P = .09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P = .33). Performance status (P = .003), nodal status (N2 v N0, P < .0001), and tumor stage (P = .0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P = .009) and shorter time to recurrence (P < .0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment.

Conclusion: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.
Prostate Cancer DNA Ploidy and Response to Salvage Hormone Therapy After Radiotherapy With or Without Short-Term Total Androgen Blockade: An Analysis of RTOG 8610
Authors: Pollack A. , Grignon D.J. , Heydon K.H. , Hammond E.H. , Lawton C.A. , Mesic J.B. , Fu K.K. , Porter A.T. , Abrams R.A. , Shipley W.U.
Published: March 2003

Purpose: DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (∼4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB).

Patients and Methods: The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival.

Results: DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation.

Conclusions: Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.