bluuebunny/crossref_metadata_2025 huggingface dataset:
EFAVIRENZ IN THE MANAGEMENT OF HIV INFECTION
Authors: Gazzard BG
Published: April 2023

Efavirenz, which is likely to be licensed in the UK and throughout Europe shortly, represents a major advance in the treatment of HIV infection. It belongs to the non‐nucleoside reverse transcriptase (NNRTI) class of drugs and, as such, it should only be prescribed with other potent therapies to avoid the development of resistance. However, in the pivotal head‐to‐head comparison of efavirenz with lamivudine and zidovudine, treatment over a 24‐week period proved superior to treatment with a standard regimen containing indinavir. The results from prolonged follow‐up of this study are eagerly awaited but it is clear that a combination of efavirenz with nucleoside analogues provides a potent proteinase inhibitor‐sparing regimen which may have less toxicity. Additional data also indicate that the combination of a proteinase inhibitor (indinavir) with efavirenz provides an extremely potent regimen which is well tolerated and produces complete inhibition of plasma HIV viraemia over prolonged periods of follow‐up. In common with many other currently available potent anti‐HIV therapies, the optimum use of this drug is being determined by ongoing clinical studies but it is clear that ease of administration (once‐daily), freedom from serious side‐effects and potency when used in combination are likely to represent a very considerable advance in the management of HIV infection.
NISOLDIPINE COAT‐CORE AND HEART RATE RESPONSE DURING TREATMENT OF HYPERTENSION
Authors: Zannad F
Published: April 2023

Nisoldipine coat‐core (nisoldipine CC), an extended‐release once‐daily formulation, is an effective treatment for mild‐to‐moderate hypertension, providing sustained blood pressure control over the 24‐hour dosing interval. Nisoldipine CC is highly vascular selective. It causes neither reflex tachycardia nor symptomatic bradycardia; it lacks significant negative inotropy at therapeutic doses; and it does not affect circadian variation in blood pressure or heart rate. Data suggest that the lack of reflex sympathetic activation in response to the blood pressure‐lowering effect of nisoldipine CC is due to the smooth onset of action of nisoldipine CC, causing resetting of the baroflex. The neutral heart rate profile of nisoldipine CC confers potential therapeutic advantages over several other calcium channel blockers, in particular, the short‐acting agents, in the treatment of hypertension.
MYOMECTOMY IN PREGNANCY: INCARCERATED PEDUNCULATED FIBROID IN AN UMBILICAL HERNIA SAC
Authors: Ehigiegba AE , Selo‐Ojeme DO
Published: April 2023

We describe a rare case of a 31‐year‐old woman at 28 weeks of pregnancy presenting with an incarcerated pedunculated fibroid in an umbilical hernia sac. She had a successful myomectomy and hernia repair and proceeded to have spontaneous vaginal delivery at term. Incarceration of a pedunculated fibroid presents a diagnostic puzzle which can be successfully treated by myomectomy.
TELEPHONE FOLLOW‐UP OF RELATIVES AFTER SUDDEN DEATH: A SURVEY OF RELATIVES' VIEWS
Authors: Stone G , Huggon A‐M , Nayeem N
Published: April 2023

The report of the Working Group on Bereavement Care in A&E departments recommended both the provision of follow‐up for relatives and the audit of bereavement care as examples of good practice. In our adult A&E department follow‐up contact is made by support workers, who have often been involved with the family at the time of death, making telephone contact four to five days later. This paper describes the role of the support workers and the results of a questionnaire sent to relatives to seek their views on this telephone follow up. In a six‐month period 98 families had relatives who died in A&E; 38 (39%) of them returned completed questionnaires. The telephone call was thought to be helpful by 37 (97%) of the respondents. The commonest reasons given were: ‘It showed you cared’ (95%) and 'It enabled me to ask questions' (46%). We have found that the experience and, more importantly, availability of the support workers allows a level of consistency and continuity in follow‐up care which can otherwise be difficult to achieve.
ATRIAL FIBRILLATION, THROMBOEMBOLISM AND ANTITHROMBOTIC THERAPY
Authors: Li‐Saw‐Hee FL , Lip GYH
Published: April 2023

Atrial fibrillation is the commonest sustained disorder of cardiac rhythm and is associated with increased risk of stroke and thromboembolic events. Warfarin (dose‐adjusted to a target INR of 2.0‐3.0) has been well established to reduce this risk of stroke by 68% (95% CI 50‐79%), while aspirin provides a risk reduction of 21% (95% CI 0‐38%). Nevertheless, warfarin confers a risk of bleeding and the inconvenience of regular monitoring checks, while aspirin seems effective only for certain low‐risk subgroups. Thus there have been strenuous efforts to improve thromboprophylaxis in atrial fibrillation, by using low‐intensity anticoagulation regimens, combination antiplatelet therapy and refinement of risk stratification strategies. Attempts at using a low‐intensity, fixed‐dose warfarin regimen have, however, been disappointing. For now, a strategy of risk stratification should be adopted to identify highest risk patients with atrial fibrillation who would benefit from anticoagulation.
EVIDENCE‐BASED MEDICINE AND OSTEOPOROSIS: A COMPARISON OF FRACTURE RISK REDUCTION DATA FROM OSTEOPOROSIS RANDOMISED CLINICAL TRIALS
Authors: Meunier PJ
Published: April 2023

The goal of osteoporosis therapy is to prevent fractures, and many therapies are available for this disease. Regarding proven fracture benefit, however, the quality of the randomised clinical trial evidence varies substantially among therapies. The purpose of this paper is, therefore, to review the published osteoporosis randomised clinical trial literature and to assess the quality of the evidence. Although more than 35 randomised trials for different therapies were reviewed, only alendronate and vitamin D plus calcium have clearly demonstrated a fracture benefit, with alendronate providing the greatest relative risk reduction. Quality clinical trial fracture data for calcitonin, etidronate, fluoride, hormone replacement therapy, parathyroid hormone, calcitriol (and other vitamin D preparations), vitamin D and calcium monotherapy, and selective oestrogen receptor modulators are either lacking or inconclusive or published only as abstracts.
BIOCHEMICAL IDENTIFICATION OF ALCOHOL ABUSE
Authors: Rosalki SB
Published: April 2023

Biochemical test abnormality can indicate chronic alcohol abuse with good clinical sensitivity and specificity. Serum gamma glutamyltransferase and carbohydrate‐deficient transferrin are the tests most frequently abnormal.
UNILATERAL ADRENAL MEDULLARY HYPERPLASIA: ANOTHER FORM OF CURABLE HYPERTENSION?
Authors: Bailey J , Vanherle AJ , Giuliano A , Schröder S
Published: April 2023

A case of unilateral adrenal medullary hyperplasia is presented in a 49‐year‐old caucasian female without multiple endocrine neoplasia association. The patient presented with episodic hypertension and paroxysms suggesting an underlying phaeochromocytoma. Biochemical supported this diagnosis but no discrete tumour was found on preoperative localising studies or at the time of surgery. The patient underwent a unilateral adrenalectomy with confirming adrenal medullary hyperplasia with complete resolution of her symptoms for six months.
PREDICTORS FOR EXTRAINTESTINAL INFECTION OF NON‐TYPHOIDAL SALMONELLA IN PATIENTS WITHOUT AIDS
Authors: Chiu CH , Lin TY , Ou JT
Published: April 2023

To identify the risks and predictors for extraintestinal infection (EII) in patients with non‐typhoidal salmonellosis, we undertook a study of 398 patients with cultures positive for non‐typhoidal Salmonella seen at Chang Gung Memorial Hospital and Chang Gung Children's Hospital between November 1993 and October 1994. Salmonella choleraesuis was the most invasive serotype observed. S. panama, S. typhimurium and S. schwarzengrund were the commonest causes of EII among those serotypes usually causing gastroenteritis. Pre‐existing underlying disease, particularly immunosuppressive disease, was the most important risk factor that may have predisposed adult patients to have EII. Old age (≥60 years) and isolation of invasive serotypes were also frequently associated with EII in adult patients. The characteristics of paediatric patients with a high probability of having EII were: <3 years of age, abnormal blood test results (a leucocyte count ≥15,0007mm3 or <5000/mm3, immature leucocytes ≥10% of total leucocytes, and a C‐reactive protein concentration ≥50 mg/l); and isolation of invasive serotypes. This information can be an aid to early diagnosis and treatment of EII caused by non‐typhoidal Salmonella.
THE EFFICACY AND SAFETY OF TELMISARTAN COMPARED TO ENALAPRIL IN PATIENTS WITH SEVERE HYPERTENSION
Authors: Neutel JM , Smith DHG , Reilly PA
Published: April 2023

This 8‐week, open‐label study compared the efficacy and safety of once‐daily telmisartan, either alone or in combination with hydrochlorothiazide (HCTZ) and amlodipine, with a similar enalapril regimen in patients with severe hypertension. Clinically relevant reductions in supine systolic blood pressure/DBP were observed with telmisartan (14.6/13.2 mmHg) and enalapril (13.0/12.9 mmHg) monotherapy. Incremental reductions were seen with up‐titration of monotherapy (telmisartan 8.1/7.4 and enalapril 9.2/7.7 mmHg), and the addition of HCTZ (telmisartan 14.9/8.7 and enalapril 8.0/6.7 mmHg), and amlodipine (telmisartan 8.0/6.5 and enalapril 10.5/6.4). After 8 weeks of treatment, supine DBP control was achieved in 55% and 35% of the patients on the telmisartan and enalapril regimens, respectively. Both treatment regimens were well tolerated. Telmisartan, a new angiotensin receptor blocker, is a safe and effective drug to use in combination for the treatment of patients with severe hypertension and proved at least as effective as the enalapril combination.
A SURVEY OF PATIENT SATISFACTION AFTER DAY CASE SURGERY
Authors: Wong LS , Kaukuntla HK , Lam FT , Fraser IA
Published: April 2023

A prospective survey of patients attending day case surgery was undertaken to determine patient satisfaction. In an eight‐week prospective study, patients undergoing procedures in the day surgical unit were asked to fill in two questionnaires, the first before surgery and the second two weeks after surgery. One hundred and eighty‐nine patients were recruited into the study; of these, 98 (52.4%) returned correctly completed forms. Most of the patients believed the information given them before surgery was adequate and the standard of care in the day unit was high. Only five patients needed to see their general practitioner because of continued problems. Twenty‐one patients felt they were discharged too early. Our current practice in day case surgery inevitably leads to some patients being discharged early. Facilities must be provided for some patients to stay longer in the day unit. Day case surgery did not result in an unacceptable increase in the workload for GPs, nor did it compromise the quality of patient care.
MANAGEMENT OF WOMEN WITH A FAMILY HISTORY OF BREAST CANCER
Authors: Curry P , Fentiman IS
Published: April 2023

Five to ten per cent of breast cancer results from an inherited germ line mutation. The main susceptibility genes are BRCA1 and BRCA2, but others include Cowden's disease, Li Fraumeni syndrome and ataxia‐telangiectasia. For those with BRCA1 or BRCA2 mutations the lifetime probability of breast cancer is between 0.40 and 0.73. Genetic testing needs to be offered to young women with breast cancer before considering testing their relatives. The efficacy of surveillance in women with genetic susceptibility has yet to be proved. The value of tamoxifen as a preventive agent in women with genetic susceptibility has yet to be confirmed. Prophylactic bilateral mastectomy will probably reduce the risk of breast cancer but this may not be absolute because of the difficulty of removing all breast tissue. New approaches may enable the selective destruction of mammary epithelium without disturbance to breast architecture.
A SUSTAINED RELEASE FORMULATION OF ISOSORBIDE‐5‐MONONITRATE WITH A RAPID ONSET OF ACTION
Authors: Arthur RMF , Mehmel H
Published: April 2023

The clinical efficacy of a combined immediate‐release and sustained‐release preparation of isosorbide‐5‐mononitrate for angina pectoris is observed within a few minutes of administration. The preparation reduces the number of silent and painful ischaemic episodes and increases work and exercise capacity. The pharmacokinetic profiles accord with the circadian variation in cardiovascular disease. Drug levels fall significantly at night and tolerance to the haemodynamic and antianginal effects is not seen. Once‐daily administration is appreciated by patients. The preparation also shows promise in treating heart failure.
5‐FLUOROURACIL‐INDUCED ERYTHEMA MULTIFORME
Authors: Lo SK , Yip D , Leslie M , Harper P
Published: April 2023

Erythema multiforme is an immunologically mediated skin reaction to a foreign antigen and can occur with many drugs. We report the first two cases of erythema multiforme induced by 5‐fluorouracil (5‐FU). The first case was in a man with inoperable gastric carcinoma being treated by continual infusion who developed the classic rash involving the neck and upper chest, along with mouth ulceration and plantar‐palmar erythrodysaesthesia. Histological confirmation was made by skin biopsy and the lesions resolved spontaneously. They recurred on restarting 5‐FU. The second case was in a woman being given adjuvant bolus 5‐FU and folinic acid for Duke's C colon cancer who developed the rash during the first cycle. Again, the lesions settled spontaneously but recurred more severely on the second cycle. When treatment was changed to the specific thymidylate synthase inhibitor, raltitrexed, the course was completed uneventfully.
LEFT‐SIDED HEPATIC HYDROTHORAX WITH ASCITES
Authors: Alagiakrishnan K , Patel PJ
Published: April 2023

Hydrothorax has long been recognised as a complication of cirrhosis, but It is seen in only a few patients, mostly on the right side. We report an unusual case of massive left‐sided hydrothorax complicating cirrhosis with ascites, where pleuro‐peritoneal communication was demonstrated on the left side by radionuclide scanning.
PERCUTANEOUS ETHANOL INJECTION THERAPY IN 47 CIRRHOTIC PATIENTS WITH HEPATOCELLULAR CARCINOMA 5 CM OR LESS: A LONG‐TERM RESULT
Authors: Lin SM , Lin D‐Y , Lin C‐J
Published: April 2023

To elucidate the long‐term results of percutaneous ethanol injection (PEI) for hepatocellular carcinoma (HCC), 47 cirrhotic patients with HCC ≤5 cm after PEI were analysed. Thirty‐two of the patients were male. The age range was 37‐68 years. Thirty‐nine patients were seropositive either for hepatitis B surface antigen or antihepatitis C virus antibody. There were a total of 61 tumours, including solitary tumours in 35 patients, double tumours in 10 and triple tumours in two. The size of the main tumour was ≤3 cm in 29 patients and more than 3 cm in 18 patients. Seventeen, 27 and three patients were in Child's class A, B and C respectively; 5‐10 ml 95% ethanol was injected into the tumour every three to seven days until the echogenicity of the tumour changed to a hyperechoic or heterogeneous one. A booster PEI was given in 34 (56%) lesions with viable tumour, which was detected by dynamic computed tomography. The one, two, three and and four‐year survival rates were 85%, 75%, 61% and 39% respectively for all patients. Good liver reserve significantly improved the survival rate (p<0.01, Child's class A and B vs Child's class C). The one, two, three and four‐year recurrence rates were 24%, 55%, 69% and 79% for all patients. HCC recurred more frequently in patients with multiple tumours (p<0.02).
TRANSPORT AND LOCALISATION OF m‐THPC IN VITRO
Authors: Kessel D
Published: April 2023

The hydrophobic photosensitising agent meta‐tetrahydroxyphenylchlorin (m‐THPC) must be formulated with an appropriate vehicle before administration. Studies were carried out with murine leukaemia cells in vitro to assess the role of formulation in drug pharmacokinetics. The rate‐limiting step in m‐THPC accumulation was the slow conversion of drug aggregates to monomers upon dilution into growth media. Only non‐viable cells with damaged membranes showed a rapid drug uptake, otherwise m‐THPC accumulation was a slow process. It was found that m‐THPC was localised mainly at mitochondrial loci. Subsequent irradiation resulted in the release of cytochrome c into the cytosol, triggering a rapid activation of caspase‐3, which led to an apoptotic response. Plasma distribution of m‐THPC involved binding to lipoprotein species, with only a slight appearance of the drug in the albumin fraction.
A COMPARISON OF VALSARTAN AND CAPTOPRIL IN PATIENTS WITH ESSENTIAL HYPERTENSION IN INDONESIA
Authors: Prabowo P , Arwanto A , Soemantri D , Sukandar E , Suprihadi H , Parsudi I , Sulaiman Markum M , Kabo P , Atmoko R , Prodjosudjadi W
Published: April 2023

Adult Indonesian outpatients were randomised to receive either valsartan 80 mg once daily or captopril 25 mg twice daily for 8 weeks. The main criterion for tolerability was the incidence of adverse events. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to endpoint. No valsartan patients experienced dry cough, which was reported by 22 captopril patients (21.6%). Both drugs reduced mean SDBP and SSBP, with a trend in favour of valsartan. The percentage of valsartan patients whose BP normalised was higher than in captopril patiente at week 4 (37% and 22%) and week 8 (45% and 34%), the difference being statistically significant at week 4 (p<0.05). Valsartan 80 mg once daily is as effective as captopril 25 mg twice daily in reducing blood pressure in Indonesian patiente, and has a better tolerability profile in respect of dry cough.
ATRIAL FIBRILLATION IN A GENERAL HOSPITAL: HOW WELL ARE WE DOING?
Authors: Bhattacharyya A , Sharma SC
Published: April 2023

Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and anticoagulation is now indicated in many patients, particularly those with congestive cardiac failure, hypertension, a history of transient ischaemic attacks or embolic stroke. In a retrospective study (and audit), we examined 280 cases of AF (acute, paroxysmal non‐sustained and chronic sustained) admitted to a general hospital in the UK. The commonest underlying medical condition was ischaemic heart disease (57%), while the commonest presenting feature was congestive cardiac failure (60%). Pharmacological cardioversion was preferred against electrical cardioversion for reverting to sinus rhythm. Fifty‐six patients (20%) received warfarin, 55 patients (20%) were on aspirin, and the remaining 169 (60%) received neither warfarin nor aspirin. More awareness is needed among physicians managing AF particularly in relation to anticoagulation.
COMPARATIVE EFFICACY OF PERINDOPRIL AND ENALAPRIL ONCE DAILY USING 24‐HOUR AMBULATORY BLOOD PRESSURE MONITORING
Authors: Yusoff K , Razak TA , Yusof N , Rafee NM
Published: April 2023

ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run‐in, double blind, crossover study, using 24‐hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4‐8 mg and enalapril 10‐20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo‐corrected peak (P) reduction of blood pressure (BP) of ‐6.4 ± 1.3 mmHg vs its placebo‐corrected trough (T) of – 5.2 ± 1.7 mmHg. Enalapril had a reduction in DBP of ‐8.5 ± 1.3 mmHg (P) and ‐5.7 ± 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of – 7.5 ± 1.6 mmHg (P) vs ‐7.3 ± 2.2 mmHg (T) compared to enalapril with ‐10.8 ± 1.6 mmHg (P) vs ‐8.3 ± 2.3 mmHg (T). Placebo‐corrected trough‐to‐peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24‐hour mean BR area under the curve or post‐dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24‐hour cover for the patient without excessive peak effect or poor trough effect.
THE TREATMENT OF METASTATIC COLORECTAL CANCER
Authors: Karapetis CS , Yip D , Harper PG
Published: April 2023

Metastatic colorectal cancer represents an incurable condition, with the exception of a very select group of patients in whom surgical excision of recurrent disease is possible. Chemotherapy offers a significant palliative benefit and may prolong patient survival. The preferred cytotoxic agent is 5‐fluorouracil, though the optimal administration schedule is unknown. Recent evidence also supports the use of second‐line chemotherapy for patients who develop progressive disease following 5‐fluorouracil treatment. Promising results have been obtained with new drugs, in particular oxaliplatin and irinotecan. Novel therapeutic approaches, including immunotherapy and liver directed strategies, are undergoing clinical evaluation. Comprehensive supportive care, with appropriate community and hospital based palliative care, is essential in the management of patients with advanced colorectal cancer.
CROHN'S DISEASE AND COLORECTAL MALIGNANCY
Authors: Kirk GR , Clements WDB
Published: April 2023

There has been much debate over the past 50 years concerning the association between colorectal carcinoma and inflammatory bowel disease. Until recently, it was widely accepted there was a higher risk in those with widespread ulcerative colitis. However, evidence now suggests an almost equal incidence in those with Crohn's disease of similar extent and duration.1 We present a case that underlines the important clinical and pathological features of Crohn's disease associated colorectal carcinoma (CDAC). We present a literature review and debate the role of regular colonic surveillance in patients with Crohn's disease affecting the colon.
SWITCH TO NON‐CFC INHALED CORTICOSTEROIDS: A COMPARATIVE EFFICACY STUDY OF HFA‐BDP AND CFC‐BDP METERED‐DOSE INHALERS
Authors: Demedts M , Cohen R , Hawkinson R
Published: April 2023

Inhaled corticosteroids, such as beclomethasone dipropionate (BDP), recommended for the treatment of persistent, mild, moderate, or severe asthma, have traditionally been administered via chlorofluorocarbon (CFC) propellant. The imminent phasing out of CFCs from pharmaceutical preparations due to the Montreal Protocol means patients will have to switch to a CFC‐free alternative. One such preparation is hydrofluoroalkane‐BDP (HFA‐BDP), a press‐and‐breathe metered‐dose inhaler. This 8‐week, open‐label, multicentre study assessed asthma control in patients switching from CFC‐BDP to HFA‐BDP (Qvar). Patients with asthma, stabilised on 400‐1600 μg/day CFC‐BDR were randomised to HFA‐BDP (354 patients; 75%) at half their current daily dose of CFC‐BDR or to CFC‐BDP (119 patients; 25%). HFA‐BDP efficacy was found to be equivalent to that of CFC‐BDP in that no statistically significant difference was observed between the two groups in the mean change from baseline in a.m. PEF (95% CI within ±11 l/min). No statistically significant differences were observed between the two groups for increased asthma symptoms or acute asthma episodes. We conclude that asthma control was maintained over 8 weeks, with few asthma exacerbations, in patients switching from previous CFC‐BDP therapy to HFA‐BDP at half the dose.
I. THE STIGMA OF EATING DISORDERS
Authors: Gowers SG , Shore A
Published: April 2023

Those who suffer from eating disorders often carry the added burden of stigmatising attitudes from the lay public and the medical profession. These attitudes not only restrict the opportunities for effective treatment but also confer additional handicaps. To some extent, stigmatising beliefs are based on partial truths about these disorders, namely their dangerousness, their sometimes poor response to treatment, the sufferers' part in their maintenance, and difficulties in communication. This review explores the truth of these beliefs and suggests ways in which a more positive approach to the management of eating disorders might help to reduce the stigma. This includes empathy with the patient's predicament and an approach to treatment in which the patient's wishes are paramount.
MUCOCOELES OF THE MAXILLARY SINUS
Authors: Jayaraj SM , Patel SK , Ghufoor K , Frosh AC
Published: April 2023

Mucocoeles of the paranasal sinuses most commonly occur in the frontal or anterior ethmoidal sinuses. We report two rare cases of mucocoele of the maxillary sinus and describe the presentation, investigations and treatment. A review of the literature on this rare clinical entity is included, with specific reference to diagnostic imaging to distinguish mucocoeles from neoplastic sinus disease.
ASYMPTOMATIC PITUITARY APOPLEXY AFTER AORTOCORONARY BYPASS SURGERY
Authors: Bhattacharyya A , Tymms DJ , Naqvi N
Published: April 2023

Pituitary apoplexy usually presents with acute neuro‐ophthalmological complications that require urgent neurosurgical intervention. We present a case of pituitary apoplexy following aortocoronary bypass surgery that was asymptomatic until the patient presented with features of hormonal deficiency three months later. Only one case of pituitary apoplexy has been described in the literature following cardiac surgery that did not require operative intervention. We discuss the aetiology of pituitary apoplexy and the possible mechanisms for such an event after cardiac surgery. Although this is rare, any unusual feature after operation such as lethargy or erectile dysfunction should remind us of hypopituitarism.
THE USE OF RECOMBINANT HUMAN G‐CSF IN THE TREATMENT OF PROPYLTHIOURACIL‐INDUCED AGRANULOCYTOSIS
Authors: Altunbas H , Yazicioglu G , Balci MK , Karayalçin Ü , Ündar L
Published: April 2023

A 43‐year‐old female patient with Basedow‐Graves' disease developed agranulocytosis in the eighth month of propylthiouracil therapy. After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony‐stimulating factor (G‐CSF), a human haematopoietic growth factor, were started. Her granulocyte count returned to normal with the second dose of G‐CSF, and ulcerating pharyngitis improved rapidly. We think that in patients with propylthiouracil‐induced agranulocytosis, G‐CSF will reduce the risk and severity of infection, and should be accepted as a part of the standard therapy.
A TRIAL OF A TEST‐AND‐TREAT STRATEGY FOR HELICOBACTER PYLORI POSITIVE DYSPEPTIC PATIENTS IN GENERAL PRACTICE
Authors: Jones R , Tait C , Sladen G , Weston‐Baker J
Published: April 2023

Computer models of different strategies for the management of dyspepsia in primary care indicate that a ‘test‐and‐treat’ approach is likely to be associated with the lowest costs and acceptable clinical outcomes. We present information on computer modelling studies and report the findings of a randomised trial comparing a Helicobacter pylori test‐and‐treat strategy with referral to direct access endoscopy in the management of dyspepsia in general practice. We compared costs and clinical outcomes in patients managed for one year in study (test‐and‐treat) and control (endoscopy) practices in south London. Patients aged less than 45 years presenting with persistent dyspepsia without alarm symptoms (141 study patients, 91 control patients) were studied. In the one‐year follow‐up period there were 17 endoscopies in the study group: all the control patients underwent initial endoscopy and five further endoscopies were performed. None revealed peptic ulcer or cancer. Forty‐three (30%) of the study patients compared with 16 (17%) of the controls were referred to hospital clinics (p<0.025). The cost of management per patient for one year in the study group was £205.67, compared with £404.31 in the control group (p<0.0001). Clinical outcomes in both groups at one year were comparable. An H. pylori test‐and‐treat strategy for dyspeptic patients aged less than 45, employing office‐based serology testing, appears to be associated with substantially lower costs than initial endoscopy and with similar clinical outcomes.
COMPARISON OF SPIRAMYCIN AND CLARITHROMYCIN FOR COMMUNITY‐ACQUIRED LOWER RESPIRATORY TRACT INFECTIONS
Authors: Ocha RTR , Awad CE , Ali A , Matyas R , Vital ACC , Silva COS , Dainesi SM , Salazar  , Nakatani J
Published: April 2023

This open multicentre study compared the efficacy and tolerability of clarithromycin and spiramycin in the treatment of lower respiratory tract infections in Brazil and Colombia. A total of 125 patients with a clinical and radiological diagnosis of pneumonia, acute bronchitis or exacerbation of chronic bronchitis were randomised to receive oral doses of either clarithromycin (500 mg) or spiramycin (3 MIL)) every 12 hours for courses of 5‐10 days. Patients were assessed before the start of treatment, and at days 3‐4 and days 9‐17. Twenty‐six (26) patients (16 in the spiramycin group and 10 in the clarithromycin group) reported adverse events, seven of whom withdrew from the trial. Statistical analysis detected no significant differences between efficacy (p=0.768) or tolerability (p=0.236) for the two treatment groups. Spiramycin therefore has similar efficacy to clarithromycin in the treatment of community‐acquired lower respiratory tract infections.
BACTERIOLOGICAL ERADICATION OF STREPTOCOCCUS PNEUMONIAE FROM PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS: CEFUROXIME AXETIL VERSUS CEFIXIME
Authors: Zuck P , Petitpretz P , Geslin P , Rio Y , Leblanc F
Published: April 2023

The bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d. or cefixime 200 mg b.d. All patients were hospitalised for an acute exacerbation of chronic bronchitis. The study design was a multicentre, double‐blind, randomised, parallel group with patients giving written informed consent initially. Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30‐75 years and had a high probability of S. pneumoniae infection based on initial sputum Gram stain. All S. pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris. S. pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p=0.002) at 2‐4 days post‐treatment. Clinical endpoints showed a similar trend – 94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1). Cefuroxime eradicated S. pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria. The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.
MEASURES FOR DECREASING INPATIENT STAY IN CHILDHOOD ASTHMA
Authors: Brown DC , South M
Published: April 2023

Traditionally, studies of asthma have concentrated on interventions that were mainly pharmaceutical and outcomes that were usually based on pulmonary function testing. More recently, there has been increasing emphasis on organisational procedures that can enhance the delivery of effective care, and outcomes based more on the clinical than the physiological. Minimum length of stay is targeted as one outcome of benefit for patients and their families. The methods of decreasing hospital stay for asthmatic children which have been proposed and studied are reviewed.
CURRENT HORMONE REPLACEMENT THERAPY: WHAT ARE THE SHORTCOMINGS? ADVANCES IN DELIVERY
Authors: Sturdee DW
Published: April 2023

The introduction of transdermal and other parenteral delivery systems has broadened the range of options for hormone replacement therapy (HRT). Oral oestrogen is the most common initial therapy; however, direct absorption of oestradiol via the skin results in an oestradiol‐oestrone ratio similar to that found in the pre‐menopausal state. Both oral and transdermal oestrogen therapy have been shown to be equally effective in relieving climacteric symptoms, and in preventing osteoporosis or modifying some cardiovascular disease risk factors, although transdermal therapy tends to have fewer unwanted effects than oral. Satisfactory circulating oestradiol levels are achieved with skin patches, transdermal gel, or crystalloid oestradiol implants, and adding progestogen to protect the endometrium is well established. Sequential therapy with HRT usually produces a regular bleed, which is a major cause of patient dissatisfaction. The ideal HRT regimen is probably unobtainable, but the development of SERMs and other regimens that avoid bleeding will encourage long‐term use.
II. STIGMA AND DEPRESSION: A DOUBLE WHAMMY
Authors: Searle GF
Published: April 2023

The burden of depression is increased by the stigma of mental illness and the widely held idea that psychoactive medication is useless and addictive. These preconceptions may delay and obscure diagnosis and reduce treatment adherence. A sensitive clinician should be able to recognise the difficulties in the individual patient and overcome them.
EXERCISE‐INDUCED RHABDOMYOLYSIS: EVEN THE FIT MAY SUFFER
Authors: Sharma N , Winpenny H , Heymann T
Published: April 2023

Keeping fit has its risks. We describe the case of a 29‐year‐old woman who presented with rhabdomyolysis following non‐exhaustive exercise. Cases of exercise‐induced rhabdomyolysis have been reported in unfit individuals or those attempting exhaustive exercise such as marathon running or weight lifting but are unusual in fit individuals making modest changes to their normal fitness routine. Renal failure is the most serious complication of rhabdomyolysis but is apparently rarer when the rhabdomyolysis is caused by exercise. Surprisingly the published literature does not help us advise patients on the risk of suffering further episodes of acute rhabdomyolysis with further exercise. We suggest that, regardless of a person's fitness, when starting a new exercise he or she does so gradually.
ELEVATED SERUM CREATINE KINASE ACTIVITY IN A PATIENT WITH ACUTE PANCREATITIS
Authors: Randeva HS , Bolodeoku J , Mikhailidis DP , Winder AD , Press M
Published: April 2023

A 62‐year‐old man presented with a five‐day history of a ‘flu‐like’ illness, epigastric pain and a state of increasing confusion. His serum values for amylase and glucose were grossly elevated, as was the creatine kinase (CK) activity, being 23 times above the upper limit of normal. CK‐MB was less than 5% of his total CK activity. There was no past history of diabetes or recent history of intramuscular injections or injury. A diagnosis of acute pancreatitis complicated by hyperosmolar non‐ketotic (HONK) diabetic pre‐coma was made. The patient was treated with intravenous fluids, insulin and subcutaneous heparin. Normal values for serum amylase and CK activity were recorded with convalescence. This case indicates a possible association of a rise in total CK activity with acute pancreatitis complicated by HONK diabetic pre‐coma. This observation was made in the absence of clinically evident muscle pathology.
LEG CRAMPS IN THE ELDERLY: PREVALENCE, DRUG AND DISEASE ASSOCIATIONS
Authors: Abdulla AJJ , Jones PW , Pearce VR
Published: April 2023

To determine the prevalence of leg cramps in elderly outpatients and their association with any underlying diseases and concomitant drug intake, we conducted a cross‐sectional study using an in‐depth questionnaire. A total of 365 patients aged 65 years and over (mean 78.5 years) attending our outpatient clinic participated in the study. The prevalence of leg cramps was 50%. Cramps were commoner in females (56%) than in males (40%). Although reported to occur anytime throughout the 24 hours, cramps were most prevalent at night (62%). In many patients, leg cramps were a long‐standing complaint: 20% had been suffering with them for more than 10 years, whereas only 9% of patients reported them first starting within the last six months. Only 73 (40%) sufferers had informed their practitioner; of these, 39 (53%) received treatment, of whom 26 gained benefit. Leg cramps were strongly associated with peripheral vascular disease (odds ratio 2.9, 95% CI 1.89‐4.55, p<0.00001), arthritis (odds ratio 2.26, 95% CI 1.48‐3.45, p=0.0001) and female gender (odds ratio 1.96, 95% CI 1.28‐3.03, p=0.002). Heart failure, hypertension, diabetes mellitus and stroke were not significantly associated. Except for a causal association with analgesic use, no positive association could be shown with any other class of drugs, including diuretics.
DOES THE ERADICATION OF HELICOBACTER PYLORI CURE DUODENAL ULCER DISEASE IN COMMUNITIES WITH A HIGH PREVALENCE RATE? COMPARISON WITH LONG‐TERM ACID SUPPRESSION
Authors: Kepekci Y , Kadayifci A
Published: April 2023

The long‐term effect of Helicobacter pylori eradication on the natural history of duodenal ulcer has been investigated and compared with long‐term acid suppression treatment in an endemic community for infection. Seventy‐three patients with endoscopically verified H. pylori positive active duodenal ulcer disease were included in this prospective study. Patients were divided into two groups. Group A patients (n=39) were given an omeprazole‐based triple eradication regimen, while group B patients (n=34) were given omeprazole alone followed by long‐term famotidine 20 mg daily as maintenance treatment. A control endoscopy was performed at the third month of treatment. The bacterium was eradicated in 32 (82%) of group A patients. All patients were followed up for two years and an endoscopy performed at the end of each year. H. pylori recurred in 13 patients and the reinfection rate was 44.8% over two years. Duodenal ulcer recurred in seven of these patients at two years (24.1%). There was a close association between H. pylori reinfection and ulcer relapse. Group B patients remained H. pylori positive during the study and the ulcer recurred in five of these patients (16.6%) despite continuous famotidine treatment. There was no statistically significant difference in ulcer relapse rate between the groups. These results suggested that H. pylori eradication is not an absolute solution for duodenal ulcer disease in high endemic regions and continuous maintenance treatment with H2‐receptor antagonists is still an alternative approach in some chronic recurrent cases.
TREATMENT WITH CARVEDILOL IS ASSOCIATED WITH A SIGNIFICANT REDUCTION IN MICROALBUMINURIA: A MULTICENTRE RANDOMISED STUDY
Authors: Fassbinder W , Quarder O , Waltz A
Published: April 2023

Patients with mild to moderate essential hypertension (n=1570) were enrolled in a large, multicentre, randomised, open‐label study designed to evaluate the safety and efficacy of different regimens of carvedilol. Reported here are the effects of carvedilol on microalbuminuria (MAU) in a subset of 876 patients who underwent MAU assessment (i.e. the Micral‐TestTM) at baseline and at week 12. MAU was present at baseline in 245 (28%) of these patients. Despite different magnitudes of blood pressure reduction, improvements in MAU were similar in all groups (range 54‐60%), with complete disappearance occurring in 48‐55% of patients. The decrease in MAU did not correlate with the magnitude of blood pressure reduction, suggesting a possible renal protective effect exerted by carvedilol independent of blood pressure reduction mediated by beta‐blockade and vasodilatation.
ACETAZOLAMIDE‐INDUCED GERSTMANN SYNDROME
Authors: Lee YT , Wu JCY , Chan FKL
Published: April 2023

Acute confusion induced by acetazolamide is a well known adverse drug reaction in patients with renal impairment. We report a case of acetazolamide‐induced Gerstmann syndrome in a patient with normal renal function, to highlight predisposing factors that are frequently overlooked.
A RARE CASE OF CUTANEOUS KAPOSIFORM HAEMANGIOENDOTHELIOMA
Authors: McPartlin DW , Ghufoor K , Patel SK , Jayaraj S
Published: April 2023

Kaposiform haemangioendothelioma is a rare vascular neoplasm with a wide anatomical distribution. We describe an unusual case arising in the post‐auricular skin of a male infant overlying a ventriculoperitoneal shunt.
ORAL GASTROGRAFIN IN NEONATES: A NOTE OF CAUTION
Authors: Tuladhar R , Daftary A , Patole SK , Whitehall JS
Published: April 2023

Hyperosmolar feeds are known to increase gastrointestinal permeability, predisposing to absorption of toxins. They are also associated with necrotising enterocolitis (NEC) in neonates. A case of a neonate with suspected NEC who died following Gram‐negative septicaemia possibly related to oral gastrografin is reported. Hyperosmolarity of gastrografin may have caused complete loss of mucosal integrity in the compromised bowel leading to Gram‐negative septicaemia.
CEFACLOR AF VERSUS AMOXYCILLIN/CLAVULANATE IN ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS: A RANDOMISED MULTICENTRE STUDY
Authors: Bandak SI , Bolzon LD , Turnak  , Johns D , Henle SK , Allen BS
Published: April 2023

Cefaclor and amoxycillin/clavulanate are active against Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus ‐ pathogens commonly associated with acute exacerbations of chronic bronchitis (AECB). This randomised, parallel‐group, single‐blind, multicentre study investigated the comparative efficacy and safety of 7‐day treatment regimens of cefaclor AF (750 mg b.d. [n=73]) and amoxycillin/clavulanate (875/125 mg b.d. [n=72]) in AECB. A favourable clinical response was obtained in 95.9% of patients on cefaclor AF and 97.2% of patients on amoxycillin/clavulanate. There were no statistically significant differences between the groups for improvement in clinical response measured by pulmonary peak expiratory flow (PPEF), or for common symptoms associated with AECB. Both agents were well tolerated, with no statistically significant differences in overall safety; however, nausea and vomiting, and abdominal pain, the most frequently occurring adverse events in the amoxycillin/clavulanate group, were not reported in the cefaclor group. In conclusion, cefaclor AF and amoxycillin/clavulanate have similar efficacy and safety profiles in the treatment of AECB.
THE EFFECT OF VALSARTAN AND CAPTOPRIL ON LIPID PARAMETERS IN PATIENTS WITH TYPE II DIABETES MELLITUS AND NEPHROPATHY
Authors: Cheung R , Lewanczuk RZ , Rodger NW , Huff MW , Oddou‐Stock P , Botteri F , Pecher E , Muirhead N
Published: April 2023

The study compared valsartan 80 mg or 160 mg o.d. with captopril 25 mg t.i.d. or placebo on plasma lipids in normotensive and treated hypertensive patients with type II diabetes and microalbuminuria. One hundred and twenty‐two adult outpatients were randomised to receive either valsartan 80 mg or 160 mg, captopril 25 mg or placebo for 360 days. Changes from baseline to endpoint in plasma lipid parameters were measured. The primary criterion for tolerability was the incidence of adverse events. All treatment groups showed minor changes in lipid parameters. Triglyceride increased by 2.7% (valsartan 160 mg) to 9.1% (placebo). Total cholesterol decreased under valsartan 80 mg, while other groups showed increases of up to 0.031 mmol/l. Decreases in total cholesterol (p=0.018), apolipoprotein B (p=0.042) and apolipoprotein A1 (p=0.025), were significant for the comparison of 80 mg valsartan and captopril. Valsartan 80 mg or 160 mg o.d. does not cause deleterious changes in the diabetic lipid profile and, unlike captopril, is not associated with dry cough.
A DOSE‐DEFINING STUDY OF SUMATRIPTAN SUPPOSITORIES IN THE ACUTE TREATMENT OF MIGRAINE
Authors: Bertin L , Brion N , Färkkilä M , Göbel H , Wessely P
Published: April 2023

In this dose‐ranging, randomised, multinational, multicentre, double‐blind, placebo‐controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p<0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p<0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14‐17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax=1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safey profile and were evaluated further.
DISSOLUTION OF THROMBUS FORMED DURING DIRECT CORONARY ANGIOPLASTY WITH A SINGLE 10 MG INTRACORONARY BOLUS DOSE OF ABCIXIMAB
Authors: Thuraisingham S , Tan KH
Published: April 2023

Direct coronary angioplasty with stent implantation is an effective treatment for acute myocardial infarction. The use of adjunctive abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist is expensive. We report on three cases of direct coronary angioplasty complicated by extensive thrombus formation that were successfully treated with attenuated dosing of abciximab via the intracoronary route. All patients presented with acute myocardial infarction complicated by cardiogenic shock or eminent cardiogenic shock. Abciximab was administered after balloon dilatation when extensive thrombus formation was noted and persisted despite repeated inflations. In all three patients a single 10 mg vial of intracoronary abciximab was administered, resulting in complete dissolution of thrombus, allowing successful deployment of stents. Thus, a single 10 mg intracoronary bolus dose of abciximab may be sufficient to achieve high local concentrations of antiplatelet activity. This facilitates thrombus dissolution and allows the safe deployment of a stent to normalise intracoronary rheology.
COMPARISON OF THERAPY WITH SIMVASTATIN 80 MG AND ATORVASTATIN 80 MG IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLAEMIA
Authors: Wierzbicki AS , Lumb PJ , Chik G , Crook MA
Published: April 2023

This study compared the efficacy of simvastatin 80 mg and atorvastatin 80 mg in the treatment of 26 patients with familial hypercholesterolaemia over 12 weeks using an open crossover trial format. Both, similarly, reduced LDL by 47 ± 13% and 43 ± 16% and median triglycerides by 22% and 27% respectively. However, atorvastatin reduced HDL by 2 ± 24% compared with 8 ± 30% increase with simvastatin (p=0.05) affecting the LDL:HDL ratio achieved (4.478 ± 1.56 vs 3.74 ± 0.93, P=0.001). Atorvastatin raised median fibrinogen by 15% compared with a non‐significant 5% increase with simvastatin (p=0.05). Simvastatin reduced lipoprotein (a) by a median 20% compared with baseline (p=0.05) compared with 5% for atorvastatin. Side‐effects, mostly gastrointestinal, were seen in four patients (16%) with atorvastatin compared with one case of myalgia with simvastatin (4%). We conclude both drugs are equally effective in LDL reduction but that simvastatin is superior in raising HDL and causes fewer side‐effects. These results require confirmation in larger studies.