bluuebunny/crossref_metadata_2025 huggingface dataset:
EICOSAPENTAENOIC ACID TREATMENT IN SCHIZOPHRENIA ASSOCIATED WITH SYMPTOM REMISSION, NORMALISATION OF BLOOD FATTY ACIDS, REDUCED NEURONAL MEMBRANE PHOSPHOLIPID TURNOVER AND STRUCTURAL BRAIN CHANGES
Authors: Puri BK , Richardson AJ , Horrobin DF , Easton T , Saeed N , Oatridge A , Hajnal JV , Bydder GM
Published: April 2023

The administration of the omega‐3 fatty acid eicosapentaenoic acid (EPA) to a drug‐naive patient with schizophrenia, untreated with conventional antipsychotic medication, led to a dramatic and sustained clinical improvement in both positive and negative symptoms. This was accompanied by a correction in erythrocyte membranes of abnormalities in both n‐3 and n‐6 highly unsaturated fatty acids and with reduced neuronal membrane phospholipid turnover, as evidenced by serial 31‐phosphorus cerebral magnetic resonance spectroscopy. Using recently developed techniques of image segmentation, subvoxel registration and quantitation, analysis of serial high‐resolution 3D cerebral MRI scans showed that, in the year before EPA treatment, cerebral atrophy was taking place and that this atrophy was reversed by six months of EPA treatment. These results demonstrate that EPA can reverse both the phospholipid abnormalities previously described in schizophrenia and cerebral atrophy. They provide strong further evidence in support of the membrane phospholipid model of schizophrenia. (Int J Clin Pract 2000; 54(1): 57‐63)
CARDIAC REHABILITATION: FROM HELLERSTEIN TO THE MILLENNIUM
Authors: Bethell HJN
Published: April 2023

In the 1950s, Herman Hellerstein set out his ideas for the comprehensive rehabilitation of patients recovering from acute cardiac events, using a multidisciplinary team. His approach has been adopted by most developed countries, with varying speeds and enthusiasm. His original ideas have hardly been improved on. However, changes in the demographics and epidemiology of heart disease have led to changes in the patient groups included in cardiac rehabilitation today and, despite falling death rates from coronary disease, the numbers who might benefit from this treatment have grown steadily. Unfortunately, only a minority of patients with heart disease who would benefit are offered rehabilitation. The provision of cardiac rehabilitation in most countries is seriously deficient, and suggestions are made for improving this situation to fulfil Hellerstein's vision. (Int J Clin Pract 2000; 54(2): 92‐97)
CARCINOMA OF THE BREAST AND HORMONE REPLACEMENT THERAPY FOR OSTEOPOROSIS
Authors: Crawshaw A
Published: April 2023

The benefits of hormone replacement therapy for postmenopausal women, especially in the prevention and treatment of osteoporosis, are well known. It is still not clear whether oestrogen replacement therapy can be given safely to women with breast cancer. The incidence and survival of breast cancer is rising in the UK and increasing numbers of young women with breast cancer treated systemically experience an early menopause and are at prolonged risk of osteoporosis. This review discusses the risk/benefit analysis of oestrogen replacement therapy for breast cancer patients, and alternative therapies: SERMs, phyto‐oestrogens and bisphosphonates. A schedule for monitoring osteoporosis for breast cancer patients with a therapeutic early menopause is suggested. (Int J Clin Pract 2000; 54(2): 99‐103)
CHEST PAIN: PANIC ATTACK OR HEART ATTACK?
Authors: Potokar JP , Nutt DJ
Published: April 2023

Chest pain is a common presentation to both primary and secondary care physicians but is often non‐cardiac in origin. Patients presenting with chest pain may be experiencing a panic attack. Panic disorder is a disabling psychiatric condition with serious consequences, such as impaired social functioning and increased risk of suicide. Comorbidity of panic disorder with other psychiatric conditions is common and often leads to increased severity of anxiety symptoms and a poorer prognosis. The cost of misdiagnosing non‐cardiac chest pain is high. It is important for physicians to be able to recognise panic attacks and to distinguish them from cardiac disease, thus avoiding unnecessary use of healthcare resources. This review discusses the prevalence and diagnosis of panic attack and panic disorder in patients presenting with chest pain to primary care physicians and cardiologists. Treatment options for panic disorder are considered, particularly the selective serotonin reuptake inhibitors, which are emerging as the first‐line choice for the treatment of panic disorder. (Int J Clin Pract 2000; 54(2): 110‐114)
THE ROLE OF TIROFIBAN IN ACUTE CORONARY SYNDROMES
Authors: Gomma A , Collinson J , Purcell H , Flather M
Published: April 2023

Platelet activation and aggregation play an important and essential role in the formation of intracoronary thrombus in acute coronary syndromes (ACS). ACS still carries unacceptably high rates of morbidity and mortality despite intensive antianginal therapy and the wide use of aspirin and heparin. Two glycoprotein IIb/IIIa receptor inhibitors are now licensed for concomitant use with heparin and aspirin in ACS. Glycoprotein IIb/IIIa receptor inhibitors block the final step for platelet aggregation and fibrinogen binding, thus preventing thrombus formation. Tirofiban is a potent, synthetic, non‐peptide and specific glycoprotein IIb/IIIa receptor inhibitor. In three major international trials involving over 7200 patients (PRISM, PRISM‐PLUS and RESTORE), tirofiban was shown to be well tolerated and to reduce the risk of ischaemic complications in patients with unstable angina, non‐Q‐wave myocardial infarction and high‐risk patients undergoing revascularisation when used in combination with aspirin and heparin. These and ongoing studies are discussed. (Int J Clin Pract 2000; 54(2): 121‐124)
MISTAKEN FIRST IMPRESSIONS: A RESPONSE
Authors: Lewis MB , Ellis HD
Published: April 2023

In this journal, Cummins et al1 reported an experiment that examined clinicians' predictions of causes of death from subjects' pre‐morbid photographs. They found that clinicians performed at chance. The validity of two of their other conclusions are challenged. First, that clinicians routinely form impressions of how a person will die from their appearance. Second, that certain health professionals use common judgements to form these impressions. These claims are found to be based upon non‐falsifiable hypothesis and inappropriate statistics; hence, an experiment employing pictures of feet (or any arbitrary personal detail) would have led the authors to the same conclusions. (Int J Clin Pract 2000; 54(2): 126‐127)
PERNICIOUS ANAEMIA AND NEUROPHYSIOLOGICAL STUDIES IN ARABS
Authors: Moussa NA , Awad MO , Yahya TM
Published: April 2023

While pernicious anaemia is a disease predominantly affecting people of north European descent, there is increasing awareness of its occurrence in other ethnic populations. We document herein details of six Arabs who had pernicious anaemia and significant neurophysiological abnormalities. All the patients made a complete haematological and symptomatic recovery following parenteral administration of hydroxycobalamin. The diagnosis of pernicious anaemia should be considered in Arab patients of all ages who have macrocytic anaemia, or symptoms of peripheral neuropathy. We caution against the empirical use of folic acid and vitamin B12 in the management of patients with chronic anaemia. (Int J Clin Pract 2000; 54(3): 152‐154)
THE WHYS AND WHEREFORES OF GETTING PATIENTS TO GIVE UP SMOKING
Authors: Pracy JP , Chevretton EB
Published: April 2023

Smoking‐related diseases are responsible for the majority of premature deaths in industrialised societies. It is 50 years since the link between smoking and lung cancer was first established, since when a gradually increasing number of smoking‐related illnesses have been identified. The treatment of patients suffering smoking‐related illnesses consumes a large proportion of health care budgets. The ever‐increasing costs of health care, in part due to the advent of new therapeutic techniques, could be offset by a concerted effort to reduce the number of people smoking. Various strategies, particularly if used in combination, have been shown to produce acceptable smoking cessation rates. At present there appears to be a reluctance on the part of governments to fund a concerted, co‐ordinated programme to encourage and assist people to stop smoking. In the absence of such support it is important for all health professionals to provide sensible advice and support to help their patients to stop smoking. (Int J Clin Pract2000;54(3): 155‐159)
THE CURRENT MANAGEMENT OF CYSTIC FIBROSIS
Authors: Lees CM , Smyth RL
Published: April 2023

Cystic fibrosis (CF) is one of the commonest lethal inherited conditions among Caucasians. It affects multiple organ systems and exhibits a range of clinical problems of varying severity. Life expectancy has improved in recent years as treatment regimes have become more intensive, but current treatments are expensive, often time consuming and may affect quality of life. This review summarises the treatments currently used in the management of patients with CF, and the evidence for these. (Int J Clin Pract 2000; 54(3): 171‐179)
AFELIMOMAB
Authors: Vincent JL
Published: April 2023

Tumour necrosis factor‐α (TNF‐α) is well established as a key mediator in the inflammatory response seen in various disease processes including sepsis. TNF‐α is involved in virtually all features of septic shock and multiple organ failure. Anti‐TNF‐α strategies are thus appealing and have been effective at reducing inflammation and morbidity in certain conditions including rheumatoid arthritis and Crohn's disease. Afelimomab is the F(ab')2 fragment of a murine anti‐TNF‐α antibody, and has been evaluated in clinical trials in septic patients. The results suggest that the drug is well tolerated, and may be of benefit in certain groups of patients with sepsis. A large, randomised, clinical trial of afelimomab in patients with severe sepsis has recently been completed and the results are eagerly awaited. More work is necessary to identify a means of selecting which patients are most likely to benefit from this type of therapy in sepsis. (Int J Clin Pract 2000; 54(3): 190‐193)
SOLITARY PLASMACYTOMA OF THE PAROTID GLAND
Authors: Hari CK , Roblin DG
Published: April 2023

Extramedullary plasmacytoma involving the parotid gland is a rare occurrence. This report describes a case of solitary extramedullary plasmacytoma arising from the parotid gland of a 60‐year‐old woman. The importance of thorough follow up for these patients is stressed, as the possibility of multiple myeloma is higher in this group. (Int J Clin Pract 2000; 54(3): 197‐198)
OSTEOID OSTEOMA OF THE SCAPULAR NECK: A CASE REPORT
Authors: Ruiz AL , Mcmullan MG , Yeates HA , Craig BF
Published: April 2023

Osteoid osteoma localised in the scapula are very rare. We report the case of an 11‐year‐old girl, who presented with an osteoid osteoma at the neck of the glenoid. This was excised en bloc after being located accurately by computed tomography. This case report demonstrates the difficulty in the approach to the excision of this unusually located lesion. (Int J Clin Pract 2000; 54(3): 199‐200)
CHRONIC HEPATITIS C BETA‐INTERFERON‐INDUCED SEVERE HYPERTRIGLYCERIDAEMIA WITH APOLIPOPROTEIN E PHENOTYPE E3/2
Authors: Homma Y , Kawazoe K , Ito T , Ide H , Takahashi H , Ueno F , Matsuzaki S
Published: April 2023

The mechanisms of hypertriglyceridaemia and changes in plasma lipoprotein subfractions by β‐interferon treatment were studied in a hepatitis C patient with apo E phenotype E3/2. Plasma levels of triglyceride (TG) were increased by treatment with 6 × 106 β‐interferon and reached 8.06 mmol/l at 4 weeks of treatment. Low energy and low fat diet reduced them to half the maximal level. Plasma levels of LDL1 (1.019<d<1.045)‐C, LDL2 (1.045<d<1.063)‐C, HDL2‐C and HDL3‐C were 0.39, 0.31, 0.21 and 0.28 mmol/l, respectively, which are low, but the plasma levels of IDL, which is a remnant of TG‐rich lipoproteins, was normal at 7 weeks of treatment. The distribution of plasma lipoprotein subfractions returned to normal after interferon treatment was discontinued. The mass and activity of lipoprotein lipase (LPL) were reduced to half the baseline level by interferon treatment. The activity of hepatic triglyceride lipase (HTGL) which transforms IDL to LDL was normal. The patient's apo E phenotype was E3/2; with that phenotype the removal of TG‐rich lipoproteins and IDL through the receptors of the remnant and LDL is impaired. But the IDL plasma level was normal, probably because of normal HTGL activity and high LDL‐receptor activity. Lymphocyte LDL‐receptor activity was double that of the control. We conclude that interferon caused the low mass and activity of LPL which in turn caused the hypertriglyceridaemia. And no retention of the remnant of TG‐rich lipoproteins in this patient with apo E3/2 and low levels of LDL subfractions was due to the active removal of them through LDL‐receptors as well as the impaired production of them by suppression of LPL by interferon. (Int J Clin Pract 2000; 54(4): 212‐216)
MANAGEMENT OF BREAST PAIN
Authors: Faiz O , Fentiman IS
Published: April 2023

Mastalgia is a common problem among premenopausal women, and those with severe and protracted symptoms merit treatment. A range of non‐hormonal and hormonal agents is available for symptom control among mastalgia sufferers but many are ineffective. Tamoxifen is the most effective and least toxic agent available for the treatment of severe chronic breast pain. Dosage with tamoxifen must be tailored to individual patient requirement and symptom control balanced against troublesome side‐effects. (Int J Clin Pract 2000; 54(4): 228‐232)
UPDATE ON VANCOMYCIN RESISTANCE
Authors: Perichon B , Courvalin P
Published: April 2023

Enterococci can be responsible for severe infections such as endocarditis, meningitis and septicaemia and are one of the most important causes of nosocomial infections. Resistance in enterococci concerns many classes of antibiotics including, since 1986, glycopeptides. These antibiotics act by blocking cell wall formation, and resistance is due to synthesis of modified peptidoglycan precursors. Resistance can be acquired or intrinsic and strains may be resistant to vancomycin and teicoplanin, or to vancomycin only. Five types of glycopeptide resistance and their biochemical mechanisms have been described. Furthermore, strains that are dependent on vancomycin for growth have been isolated from clinical samples. Data suggest that resistance could originate in glycopeptide‐producing organisms or in enterococcal species intrinsically resistant to these antibiotics. (Int J Clin Pract 2000 54(4): 250‐254)
TRANSIENT PATHOLOGICAL Q WAVES IN SUSPECTED ACUTE MYOCARDIAL INFARCTION: ‘ELECTRICAL STUNNING’
Authors: Banerjee S , Hargreaves
Published: April 2023

In acute coronary syndromes the development of pathological Q waves is usually taken as evidence of established myocardial infarction (MI). We describe two patients with suspected acute Ml who developed transient pathological Q waves. Cardiac enzymes were normal and cardiac catheterisation showed severe proximal coronary disease. Recognition of ‘non‐infarction’ Q waves is important and may influence management of these patients. (Int J Clin Pract 2000; 54(4): 263‐264)
A CLINICAL COMPARISON OF SUMATRIPTAN NASAL SPRAY AND DIHYDROERGOTAMINE NASAL SPRAY IN THE ACUTE TREATMENT OF MIGRAINE
Authors: Boureau F , Kappos L , Schoenen J , Esperanca P , Ashford E
Published: April 2023

A multinational, multicentre, randomised, double‐blind, double‐dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p<0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p=0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p=0.037) and relief of nausea (55% sumatriptan, 40% DHE, p=0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. lt is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache. (Int J Clin Pract 2000; 54(5): 281‐286)
LOW DENSITY LIPOPROTEIN CHOLESTEROL LOWERING: ARE THE TREATMENT GUIDELINES STILL APPROPRIATE?
Authors: Deslypere J‐P
Published: April 2023

The availability of treatment guidelines has revolutionised our approach to detection, evaluation and treatment of dyslipidaemias in adults. Such guidelines focus on lowering low‐density lipoprotein‐cholesterol (LDL‐C), the primary risk factor for coronary heart disease, and provide physicians with specific goals to be attained by dietary and, if necessary, pharmacological therapy. However, the guidelines were published in 1993, which means that the pivotal findings from large intervention trials with statins were not included. This has led to calls for the guidelines to be amended to take into account the findings of these studies and other evolving issues such as the pathogenesis of the acute coronary event and the contribution of low HDL‐C and other lipid parameters. More importantly, the mostly epidemiological basis of the guidelines has instilled the concept that the lower the LDL‐C level after lipid‐lowering intervention the better the result in terms of prevention of coronary events. Available data now refute this assumption. Indeed, maximal therapeutic benefit is already obtained with a decrease in LDL‐C level of 20‐30%, irrespective of baseline levels or LDL‐C levels on treatment and, until now, there have been no data to suggest that decreases in LDL‐C of >30% give any additional benefit to patients in terms of improving their long‐term outcome. The concept of absolute LDL‐C treatment goals therefore needs to be revisited. A more appropriate goal of lipid‐lowering therapy with statins is to ensure LDL‐C levels are reduced by 20‐30%, with statin dosages as used in the intervention trials. Furthermore, there are insufficient data to advise that LDL‐C levels should be lowered to 2.6 mmol/l. This issue will be resolved only when the results of the appropriate intervention trials are published. (Int J Clin Pract 2000; 54(5): 307‐313)
HYPERMOBILITY ‐ NOT A CIRCUS ACT
Authors: Grahame R
Published: April 2023

Joint hypermobility results from genetic variations in connective tissue matrix proteins resulting in stretchier tissues. For many it is an asset that confers greater facility for physical prowess. Others, less fortunate, fall prey to the associated effects of tissue fragility. The most frequently encountered constellation of traumatic and overuse injuries is termed the (benign joint) hypermobility syndrome (BJHS). This condition, poorly understood, frequently overlooked, misdiagnosed and inappropriately treated, is the cause of much needless suffering and anguish. Accumulating evidence suggests that BJHS represents a forme fruste of an heritable disorder of connective alongside Marfan syndrome, Ehlers‐Danlos syndrome and osteogenesis imperfecta, with which it shares many overlapping features, but from which it can be phenotypically distinguished on the basis of clinical features and prognosis. The responsible gene defects have yet to be elucidated. (Int J Clin Pract 2000; 54(5): 314‐315)
ANAPHYLAXIS AND ANAPHYLACTOID REACTIONS
Authors: Murrant T , Bihari D
Published: April 2023

The clinical syndrome of anaphylaxis and anaphylactoid reactions is quite variable, making diagnosis difficult at times. Early recognition by patient or physician is imperative to appropriate management. Recurrences may be life‐threatening if the initial diagnosis is incorrect, as patients do not avoid the offending allergen. Release of inflammatory mediators from mast cells and basophils are responsible for the symptoms and signs in both anaphylactic and anaphylactoid reactions. They differ only in the initial cause of the activation of the mast cell or basophil. Management, regardless of the cause, involves rapid treatment. Intravenous fluids and adrenalin (preferably intravenous if appropriate) usually produce a response in more than 90% of patients. Prevention strategies including pharmacological prophylaxis should not be undervalued, because recurrences can easily be avoided. Follow‐up with an allergist/immunologist is essential.(Int J Clin Pract2000;54(5):322‐328)
REFRACTORY BACILLUS CEREUS INFECTION IN A NEONATE
Authors: Tuladhar R , Patole SK , Koh TH , Norton R , Whitehall JS
Published: April 2023

Bacillus cereus is a Gram‐positive aerobic or facultatively anaerobic spore‐forming rod, which usually causes food poisoning. Its recognition as a pathogen in neonates has increased over the past two decades. The clinical course of a neonate (gestation 24 weeks) with B. cereus infection refractory to therapy is described. Death occurred after withdrawal of support following persistently positive blood and bone marrow cultures despite therapy with vancomycin, gentamicin, imipenum, clindamycin, ciprofloxacillin, immunoglobulin and granulocyte colony stimulating factor over a period of 49 days. No obvious focus of sepsis was identified. Contamination from the environment into the hospital and clinics occurs because of the ubiquitous presence of B. cereus. Combination therapy with vancomycin and gentamycin is appropriate for meningitis/severe systemic infections related to most bacillus species. The significance of repeated isolation of B. cereus in neonates with compromised host defences is emphasised. (Int J Clin Pract 2000; 54(5): 345‐347)
CEFTRIAXONE‐PMMA BEADS – A SLOW RELEASE PREPARATION?
Authors: Alonge TO , Fashina AN
Published: April 2023

The use of various drug delivery systems to achieve high levels of the desired antibiotic(s) at the site of infection has become commonplace in orthopaedic and trauma units the world over. One of these techniques uses the implantation of antibiotic‐impregnated beads at operation sites. Commercial antibiotic beads such as the gentamicin bead are available but expensive, especially for patients in developing countries. We have shown that ceftriaxone‐polymethylmethacrylate beads can be produced locally and at low cost in a resource‐poor environment. We have also shown that such beads elute the antibiotic (ceftriaxone) effectively in vitro, achieving similar or better activity when measured by zones of inhibition against various bacteria species compared with standard antibiotic discs. This technique offers a cost‐effective method of treating chronic bone infections in resource‐poor settings. (Int J Clin Pract 2000; 54(6): 353‐355)
ADVANCES IN NON‐OPERATIVE THERAPY IN PANCREATIC CANCER
Authors: Ammer R BR , Buckels J , Bramhall S
Published: April 2023

Pancreatic cancer is the fifth leading cause of cancer death in the western world. The majority of patients present with advanced disease and only a few have resectable disease at presentation. This paper reviews current evidence supporting the use of conventional chemotherapy and radiotherapy in advanced disease; it goes on to review the rationale and how these data have influenced the use of radiochemotherapy in the adjuvant setting. Unpublished data from the largest adjuvant study of chemoradiotherapy in pancreatic cancer are also presented. The role of neoadjuvant therapy is discussed and how trials using this approach are evolving in pancreatic cancer. The paper finishes by reviewing the use of marimastat, a novel agent that has been extensively studied in patients with pancreatic cancer. Pancreatic cancer remains a challenge to clinicians, but increases in sub‐specialisation and a renewed interest in the disease has made the future for patients more encouraging than at any time in the past. (Int J Clin Pract 2000; 54(6): 373‐381)
REVIEW OF OXALIPLATIN: AN ACTIVE PLATINUM AGENT IN COLORECTAL CANCER
Authors: Cassidy J
Published: April 2023

Oxaliplatin is a novel platinum analogue which has wide spectrum anti‐cancer activity in in vitro systems. It has distinct biochemical, pharmacological and cytotoxic properties which are different from those of cisplatin and carboplatin. Importantly, it appears to have distinct mechanisms of resistance such that traditionally platinum insensitive tumour types may be susceptible to oxaliplatin. Most notable in this regard is the activity of this agent which has been demonstrated in colorectal cancer. This review concentrates on this aspect of oxaliplatin. Oxaliplatin has modest activity as a single agent in advanced colorectal cancer compared with other novel agents in this disease. However, there appears to be a powerful synergy between oxaliplatin and 5‐fluorouracil. Thus, when given together, response rates of over 50% are consistently observed. The combination has now been extensively tested in this disease and has recently led to the regulatory approval for marketing of oxaliplatin in this condition. (Int J Clin Pract 2000; 54(6): 399‐402)
PERGOLIDE‐INDUCED RETROPERITONEAL FIBROSIS
Authors: Mondal BK , Suri S
Published: April 2023

Retroperitoneal fibrosis is a rare complication of pergolide therapy. This complication can be easily missed, so it is essential to have a high index of suspicion. We describe a case of well controlled Parkinson's disease who presented with shortness of breath and oedema. (Int J Clin Pract 2000; 54(6): 403)
CHRONIC ISOLATED VERTIGO
Authors: Chan LL , Tan E‐K , Tan K‐P
Published: April 2023

Vertigo can be the first manifestation of vertebrobasilar ischaemia or brainstem and cerebellar stroke. Chronic isolated vertigo may pose a diagnostic dilemma. We report the case of a patient who presented with chronic isolated vertigo, and highlight the clinical use of magnetic resonance imaging and angiography in his management. (Int J Clin Pract 2000; 54(6): 407‐408)
VERAPAMIL SR AND TRANDOLAPRIL COMBINATION THERAPY IS SAFE AND EFFECTIVE IN HYPERTENSIVE PATIENTS WITH METABOLIC DISORDERS
Authors: Aksöyek S , Özer N , Aytemir K , Kes S ,   Turkish Multicentre Verapamil and Trandolapril Study Group
Published: April 2023

Verapamil SR (180 mg) plus Trandolapril (2 mg) is a potent antihypertensive combination but the efficacy and safety of this treatment has not been studied fully in hypertensive patients with metabolic disorders. We enrolled 298 patients with mild to moderate hypertension who had at least one of the following disorders: diabetes mellitus, hypercholesterolaemia or mild renal failure. The sitting systolic pressure and diastolic blood pressures were significantly decreased after 12 weeks of treatment. Blood pressure was inadequately controlled in only 24 patients (8.8%). Progressive decreases in blood glucose, total cholesterol, low‐density lipoprotein and triglyceride levels were observed during the study. There was no significant change in blood urea nitrogen, creatinine and transaminase levels (p>0.05). There was a significant decrease in microalbuminuria levels. There was no significant change in glycosylated haemoglobin levels in diabetic patients. Verapamil SR plus trandolapril is an effective drug combination in the treatment of hypertension. It may be used safely in patients with diabetes mellitus, hyperlipidaemia and mild renal failure.
IDENTIFYING PRIORITY PATIENTS FOR CORONARY ANGIOGRAPHY
Authors: Azeem T , Vassallo M , Smith E , Martin MA
Published: April 2023

We conducted an open observational study with blinded endpoint evaluation to validate the use of the Duke treadmill score in identifying patients likely to require coronary intervention. We studied 101 consecutive patients referred for coronary angiography from a cardiology clinic. All patients had a Bruce protocol exercise test. A 70% stenosis was regarded as significant. Patients were referred for percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) surgery, if indicated. The Duke score was calculated as follows: exercise time (min) – (5 × ST segment deviation [mm]) – (4 × angina index [text]). Patients were classified into low, medium and high risk. The patients at high risk are more likely to have a significant stenosis (53/58 vs 30/43: p=0.01 [OR 4.59 95% CI 1.34–16.6]) and require CABG or PTCA (47/58 vs 16/43: p<0.001 [OR 7.21 95% CI 2.69–19.8]) than those at medium/low risk. Multiple logistic regression analysis, including ST segment depression, exercise time and symptoms shows that the score independently predicts a significant stenosis (p=0.002) and the need for coronary intervention (p=0.001). Introducing the score can help to identify those patients who need priority investigation.
CONSIDERATIONS FOR DRUG THERAPY IN HYPERTENSION
Authors: McNally P
Published: April 2023

Both the Joint National Committee and the British Hypertension Society recommend b‐blockers and diuretics as first‐line therapy in the treatment of uncomplicated hypertension. As a result, many clinicians will also prescribe these drugs in the treatment of patients with hypertension and coexistent disease (unless they are specifically contraindicated), even though they may not always be the most beneficial choice. This review aims to examine factors that should be taken into consideration when choosing appropriate antihypertensive therapy. Particular attention is given to treatment options in two special patient groups, the elderly and patients with co‐morbid diabetes, as these groups have an increased risk of developing cardiovascular complications. In response to the increasing evidence base from large‐scale trials, the article concludes that cardiovascular risk factors, coexisting disease, concomitant medication and age should all be taken into account when choosing antihypertensive therapy.
CONSENSUS FOR THE PHARMACOLOGICAL MANAGEMENT OF INSOMNIA IN THE NEW MILLENNIUM
Authors: Roth T , Hajak G , Üstün TB
Published: April 2023

Insomnia, a common symptom throughout the world, is characterised by difficulty initiating or maintaining sleep or non‐restorative sleep and is associated with significant morbidity. A comprehensive medical and sleep history and physical examination are necessary before treating patients with insomnia; the presence of co‐morbidities, including medical and psychiatric disorders, or the possible use of substances that may contribute to sleeplessness should be thoroughly investigated. Non‐pharmacological approaches include correction of sleep hygiene as well as behavioural treatments. Pharmacotherapy includes benzodiazepine‐receptor agonists, which are the drugs of choice for this disorder. They can be subdivided into classic benzodiazepines and non‐benzodiazepines. Although many agents in these classes have been prescribed, potential shortcomings include residual sedation, rebound insomnia, and psychomotor and memory impairment. Novel pharmacological strategies that address limitations of the traditional treatment approach, combined with proven modes of behavioural therapy, offer the most successful results in the management of insomnia. These advances provide the opportunity to establish these current recommendations for the optimal management of insomnia. This report from the XXII Collegium Internationale Neuro‐Psychopharmacologicum Consensus Workshop outlines recommendations to serve as the foundation for developing a therapeutic plan for each patient.
LINEZOLID
Authors: French G
Published: April 2023

Multiple antibiotic resistance is increasing worldwide in Gram‐positive bacteria, especially in hospitals. Problem organisms include multiply resistant strains of pneumococci,Staphylococcus aureusand enterococci; for many of these the glycopeptide vancomycin has become the treatment of last resort. This situation has been made worse by the emergence of vancomycin‐resistant enterococci and vancomycin‐intermediateS. aureus.Fortunately, several compounds active against resistant Gram‐positive bacteria are in active development. One of these is linezolid, the first of the oxazolidinones, a new class of antibacterial. Linezolid is a synthetic agent which is active against all the clinically important Gram‐positive bacteria, including multiply resistant strains. It has good pharmacokinetics, with equal bioavailability by both oral and intravenous routes and no need for dose adjustment in patients with renal impairment. The drug has a good safety profile and clinical trials have given excellent results in a variety of skin and soft tissue, respiratory and bloodstream infections. Linezolid is a promising drug, which, together with prudent antibiotic use and the prevention and control of hospital infection, will help in the battle against multiply antibiotic resistant Gram‐positive bacteria.
A CASE OF VOLUMINOUS DIARRHOEA WITH HYPOKALAEMIC ACIDOSIS
Authors: Abdelgabar A , Owen A , Starczewski A , Subashchandran R
Published: April 2023

We describe a patient presenting with voluminous diarrhoea, hypokalaemic acidosis and hypercalcaemia who was found to have a vasoactive intestinal polypeptide‐producing tumour. His diarrhoea was initially mild and intermittent requiring no medical attention.
GLOSSAL PALPATION OF THE EUSTACHIAN TUBE CUSHION: AN UNUSUAL CAUSE OF GLOBUS SENSATION
Authors: Motamed M , Murty GE
Published: April 2023

Globus sensation, the sensation of a lump in the throat, is a common symptom which, in its chronic form, accounts for 4% of first‐patient visits to ENT clinics. We describe a rare cause of globus sensation and stress the importance of thorough investigation to exclude any possible organic causes.
CARDIOGENIC SHOCK FOLLOWING A SINGLE THERAPEUTIC ORAL DOSE OF VERAPAMIL
Authors: Stajer D , Bervar M , Horvat M
Published: April 2023

Cardiogenic shock and apnoea appeared in a 78‐year‐old woman with a history of biventricular heart failure, following ingestion of a single 80 mg verapamil tablet. She was resuscitated with artificial ventilation, dobutamine, norepinephrine and calcium gluconate. Toxicological analysis revealed unexpectedly high plasma verapamil concentration, which was attributed to the patient's liver failure. In patients with advanced heart failure a single oral therapeutic dose of verapamil may have a severe toxic effect.
THE OLD BUT RELIABLE DIGITALIS: PERSISTENT CONCERNS AND EXPANDED INDICATIONS
Authors: Abarquez RF
Published: April 2023

Digitalis has been an old but reliable drug for 240 years. Concerns regarding its clinical indications and benefits still exist in the absence of a reduction in all‐cause mortality. While intravenous digitalis is used without question in cases of atrial fibrillation, it is still controversial in sinus rhythm, despite the Digitalis Investigation Group (DIG) study showing a significant reduction in death and the need for hospitalisation for congestive heart failure in both diastolic and systolic dysfunction. The influence of digitalis in acute myocardial infarction, coronary artery disease and sudden cardiac death remains speculative. In cases of uncomplicated hypertension, it appears to prevent the onset of left ventricular dysfunction and myocardial infarction. Thus, digitalis can be a cost‐effective agent with added benefits.
THREE‐YEAR UPDATE OF SILDENAFIL CITRATE (VIAGRA®) EFFICACY AND SAFETY
Authors: Sadovsky R , Miller T , Moskowitz M , Hackett G
Published: April 2023

In the three years since its launch, sildenafil citrate (Viagra®), an oral agent for the treatment of erectile dysfunction (ED), has been prescribed to more than 10 million patients worldwide and has been further evaluated in clinical studies in diverse patient populations. Significant improvements in erectile function have been demonstrated in double‐blind, placebo‐controlled trials in patients with ED and underlying diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. Promising results have also been reported for patients with treated prostate cancer, end‐stage renal failure, Parkinson's disease, and spina bifida and in multiple organ transplant recipients. Accounts of sildenafil use in clinical practice and postmarketing data reflect clinical trial findings of effectiveness in a broad spectrum of ED aetiologies and overall good tolerability. As in the clinical trials, most adverse events associated with sildenafil use have been transient, mild or moderate effects that rarely lead to treatment discontinuation.
SIMILAR EFFICACY FOLLOWING FOUR WEEKS TREATMENT OF ASTHMATICS WITH FORMOTEROL 12 μG B.D. DELIVERED BY TWO DIFFERENT DRY POWDER INHALERS: DIFFERENCES IN INHALER HANDLING
Authors: Eliraz A , Ramirez‐Rivera A , Ferranti P , Holzer R , Garcí JM Ignacio , Turcotte C , Rapatz G , Pfister P , Overend T , Kottakis J
Published: April 2023

This randomised, multicentre, parallel‐group study compared the clinical efficacy and ease of handling of two dry powder inhalers delivering the long‐acting β2‐agonist formoterol. After run‐in, 200 asthmatics on treatment with inhaled corticosteroids and still presenting with suboptimal asthma control were randomised to receive 12 μg formoterol twice daily via either the Aerolizer inhaler (Foradil® Aerolizer™) or the Turbuhaler inhaler (Oxis® Turbuhaler®) for four weeks. Study variables included the mean morning pre‐medication peak expiratory flow (PEF) during the last seven days of treatment and the correct inhaler handling according to inhaler‐specific checklists. The mean difference in the effect on morning pre‐medication PEF was 13.86 l/min in favour of formoterol via the Aerolizer inhaler (90% confidence interval 2.50, 25.21) in the intent‐to‐treat population. Eighty‐six per cent of the patients under treatment with formoterol via the Turbuhaler inhaler performed correctly all the essential inhalation manoeuvres, whereas 98% of those on the Aerolizer inhaler did so. These results strongly suggest similar clinical efficacy with twice daily treatment of formoterol 12 μg metered dose delivered either by the Aerolizer, or the Turbuhaler device. They also suggest that handling the Aerolizer is easier than that of the Turbuhaler.
EFFICACY AND SAFETY OF SILDENAFIL CITRATE FOR THE TREATMENT OF ERECTILE DYSFUNCTION IN MEN WITH CARDIOVASCULAR DISEASE
Authors: Olsson AM , Persson C‐A
Published: April 2023

Men with cardiovascular disease (CVD) are more likely to have erectile dysfunction (ED) than the general population, as both conditions share risk factors and some drugs used to treat CVD may induce ED as a side‐effect. This study was undertaken to assess the efficacy and safety of sildenafil citrate for the treatment of ED in men with CVD who were receiving treatment with β‐blockers and/or angiotensin‐converting enzyme inhibitors and/or calcium‐channel blockers, but not nitrates. Treatment with sildenafil was associated with significant increases in the mean end‐of‐treatment scores for the questions from the International Index of Erectile Function that assess the ability to achieve and maintain erections (p=0.0001). Furthermore, 71% of patients taking sildenafil reported improved erections compared with 24% taking placebo (p=0.0001). This study also showed that sildenafil was well tolerated in patients with CVD and ED. Besides flushing, no treatment‐related cardiovascular adverse events were noted for sildenafil.
PHOSPHODIESTERASE 5 INHIBITION: EFFECTS ON THE CORONARY VASCULATURE
Authors: Jackson G
Published: April 2023

As a potent and selective inhibitor of cyclic guanosine monophosphate‐specific phosphodiesterase 5 (PDE5), sildenafil citrate (Viagra®) is safe and effective in men with erectile dysfunction (ED) of diverse aetiologies, including patients with common cardiovascular diseases who are not receiving organic nitrates or nitrate donor drugs. In retrospective analyses of extensive clinical trials, sildenafil treatment for ED was not associated with any increase in cardiac risk. In haemodynamic studies, sildenafil produced small decreases in systemic and pulmonary blood pressure but caused no adverse cardiovascular effects in specific populations of men with coronary heart disease. Sildenafil also caused no significant changes in coronary blood flow but had a positive effect on coronary flow reserve in men with severe coronary artery disease. Together with findings from other studies, these data suggest that PDE5 may play an important role in the regulation of coronary blood flow in the healthy and diseased heart.
CORONARY ARTERY DISEASE IN PATIENTS WITH RENAL FAILURE
Authors: Goldsmith DJA , Covic A
Published: April 2023

Cardiovascular disease is prevalent in patients with advanced renal failure or on dialysis treatment, and after renal transplantation. The risk factors for the cardiovascular problems are a mixture of conventional and novel ones. Inflammation and oxidation may be especially important in the acceleration of atherosclerosis in chronic renal failure. This article discusses these factors and gathers together the evidence for cardiovascular intervention and treatment in a group of patients whose overall mortality is high.
ALEXIA WITHOUT AGRAPHIA: A CENTURY LATER
Authors: Imtiaz KE , Nirodi G , Khaleeli AA
Published: April 2023

A case of alexia without agraphia is presented. It is a rare but classic disconnection syndrome, first described by Dejerine in 1892. Recent advances in modern neuroimaging techniques such as FLAIR MRI can now localise in vivo the site of origin of the syndrome, especially when computerised axial tomogram of the brain is normal.
DICE 2: A FURTHER INVESTIGATION OF THE EFFECTS OF CHANCE IN LIFE, DEATH AND SUBGROUP ANALYSES
Authors: Clarke M , Halsey J
Published: April 2023

In an investigation into how chance might influence the distribution of deaths in a randomised trial and the time of those deaths, and to highlight the possible dangers of subgroup analyses, 100 randomised controlled trials were simulated and 50 subgroup pairs were simulated for some of these trials. Each of 580 control patients from a colorectal cancer trial was randomly coded to simulate allocation to treatment or control, the main outcome measure being time to death. Not surprisingly, most of the 100 trials gave non‐significant results. Four were conventionally significant with logrank 2p‐values of less than 0.05. The most extreme result was associated with a logrank 2p‐value of 0.003, showing an absolute reduction in four‐year mortality of 40% (SD 15) for patients allocated to treatment. One of the simulated prognostic factors for this trial (subgroup 13) showed that mortality for one type of patient was non‐significantly slightly increased by treatment, whereas treatment reduced four‐year mortality by 64% (SD 16) among the other patients in the trial (2p=0.00006). Similar, extreme results were found for a trial of borderline statistical significance overall. Chance can influence the overall results of any randomised controlled trial, regardless of how well it is conducted, and can play an even more powerful role in the results of subgroup analyses. This should be borne in mind both by trialists when reporting their results and by readers and reviewers of those reports.
AETIOLOGY AND TREATMENT OF HYPERHOMOCYSTEINAEMIA CAUSING ISCHAEMIC STROKE
Authors: Sarkar PK , Lambert LA
Published: April 2023

Recent studies have shown that hyperhomocysteinaemia is a common, independent and easily modifiable risk factor for atherosclerotic and thromboembolic diseases such as cerebrovascular disease, coronary artery disease and venous thrombosis. The vascular risk rises continuously across the spectrum of elevated plasma homocysteine concentrations. It is at least as important as cholesterol, lipoprotein abnormalities and hypertension and should be part of risk assessment, especially those at high risk. Moderately elevated plasma homocysteine concentration is readily correctable by folic acid, betaine, or vitamin B12 supplementation. It seems logical to assume that a reduction in homocysteine concentration will reduce the risk of ischaemic stroke, but there are as yet no published data to prove this. This review will discuss the aetiology and possible treatment of hyperhomocysteinaemia causing ischaemic stroke.
C‐REACTIVE PROTEIN
Authors: Rosalki SB
Published: April 2023

C‐reactive protein (CRP) is a protein whose concentration in serum is increased in response to inflammatory stimuli. Increased levels serve to identify organic disease, monitor disease activity and assist differential diagnosis. High values are observed early in bacterial infections, active rheumatoid disease, Crohn's disease, acute myocardial infarction and after major trauma. In patients with ischaemic chest pain, a raised CRP value on hospital admission is associated with an adverse prognosis. In apparently healthy individuals, a raised CRP value indicates an increased risk of developing atherosclerotic vascular disease, but also increased benefit from aspirin prophylaxis and treatment of hyperlipidaemia.
A STUDY OF THE APPROPRIATENESS OF ANTIBIOTIC USE IN THE MEDICAL WARDS OF A TERTIARY TEACHING HOSPITAL IN MALAYSIA
Authors: Hooi PY , Yong CM , Cheong I
Published: April 2023

A prospective study was conducted to determine the proportion of patients who received an antibiotic within 12 hours of admission to the medical wards. During the four‐week study, 234 patients were admitted to medical wards from casualty; 68 patients (29%) received an antibiotic. The survey indicated that antibiotics were inappropriate in 22–65% of those treated. This study also shows that as many as 67% of patients who received intravenous antibiotics could have been equally well treated with oral preparations.
MOXIFLOXACIN VERSUS AMOXYCILLIN CLAVULANATE IN THE TREATMENT OF ACUTE MAXILLARY SINUSITIS: A PRIMARY CARE EXPERIENCE
Authors: Rakkar S , Roberts K , Towe BE , Elores SM , Heyd A , Warner J
Published: April 2023

In this prospective, multicentre, randomised, non‐blinded phase III clinical trial, 475 adult patients with acute sinusitis received a 10‐day oral regimen of either moxifloxacin (400 mg once daily) or amoxycillin clavulanate (875 mg twice daily). The primary measure of efficacy was clinical resolution. Secondary outcome measures included clinical relapse at follow‐up and evaluation of patient reported outcomes. Of 471 adults comprising the intent‐to‐treat population (234 moxifloxacin, 237 amoxycillin/clavulanate), moxifloxacin treatment was statistically equivalent to amoxycillin/clavulanate at the test‐of‐cure visit (85% vs 82%; 95% CI ‐6%, 13%). Analysis of the efficacy evaluable population, confirmed statistical equivalence (86% vs 84 %; 95% CI ‐7%, 13%). Of note, by day 3 of treatment, significantly more moxifloxacin‐treated patients (n=47; 24%), than amoxycillin/clavulanate‐treated patients (n=28; 14%), reported feeling better (p<0.02). Frequency of drug‐related adverse events were similar between groups: nausea (11% moxifloxacin, 5% amoxycillin/clavulanate) and diarrhoea (3% moxifloxacin, 10% amoxycillin clavulanate). In conclusion, once‐daily moxifloxacin is as effective and safe as twice‐daily amoxycillin/clavulanate in the treatment of acute sinusitis. Moxifloxacin is associated with more rapid symptomatic relief.
SEVERE BRADYARRHYTHMIA IN A PATIENT WITH ALZHEIMER'S DISEASE AND A PATIENT WITH CEREBRAL ISCHAEMIA, BOTH INDUCED BY ACUTE DISTENSION OF THE BLADDER
Authors: Koch HJ , Szecsey A , Raschka C
Published: April 2023

Two case reports are presented of bradycardia in two elderly patients, which was resistant to atropine but which resolved immediately the acute bladder distension was treated. Generally, a sympathetic cardiac response is expected, and this paradoxical response may be due not only to lesions of the reflex loop involving both the vagal and the sympathetic nerves, but also to endocrinological factors. As acute urinary distension is not uncommon on geriatric wards, bradyarrhythmia due to bladder distension should be considered in elderly patients.