Showing papers in "QJM: An International Journal of Medicine in 2001"

Validation of a modified Early Warning Score in medical admissions

Abstract: The Early Warning Score (EWS) is a simple physiological scoring system suitable for bedside application. The ability of a modified Early Warning Score (MEWS) to identify medical patients at risk of catastrophic deterioration in a busy clinical area was investigated. In a prospective cohort study, we applied MEWS to patients admitted to the 56-bed acute Medical Admissions Unit (MAU) of a District General Hospital (DGH). Data on 709 medical emergency admissions were collected during March 2000. Main outcome measures were death, intensive care unit (ICU) admission, high dependency unit (HDU) admission, cardiac arrest, survival and hospital discharge at 60 days. Scores of 5 or more were associated with increased risk of death (OR 5.4, 95%CI 2.8-10.7), ICU admission (OR 10.9, 95%CI 2.2-55.6) and HDU admission (OR 3.3, 95%CI 1.2-9.2). MEWS can be applied easily in a DGH medical admission unit, and identifies patients at risk of deterioration who require increased levels of care in the HDU or ICU. A clinical pathway could be created, using nurse practitioners and/or critical care physicians, to respond to high scores and intervene with appropriate changes in clinical management.

Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis

Abstract: Offspring of women with pregestational diabetes mellitus are at increased risk for congenital malformations, largely attributable to poor periconceptional glycaemic control. We assessed the effect of preconception care in reducing congenital malformations, in a meta-analysis of published studies of preconception care in women with diabetes mellitus. Articles were retrieved from Medline (1970 to June 2000) and Embase (1980 to June 2000), and data abstracted by two independent reviewers. The rates and relative risks (RR) for major and minor congenital malformations were pooled from all eligible studies using a random effects model, as were early first-trimester glycosylated haemoglobin values. In 14 cohort studies, major congenital malformations were assessed among 1192 offspring of mothers who had received preconception care, and 1459 offspring of women who had not. The pooled rate of major anomalies was lower among preconception care recipients (2.1%) than non-recipients (6.5%) (RR 0.36, 95%CI 0.22-0.59). In nine studies, the risk for major and minor anomalies was also lower among women who received preconception care (RR 0.32, 95%CI 0.17-0.59), as were the early first-trimester mean glycosylated haemoglobin values (pooled mean difference: 2.3%, 95%CI 2.1-2.4). Women who received preconception care were, on average, 1.8 years older than non-recipients, and fewer smoked (19.6% vs. 30.2%). Only one study described the routine use of periconception folic acid. Out-patient preconception care probably reduces the risk of major congenital anomalies among the offspring of women with pregestational diabetes mellitus. Because many women with diabetes neither plan their pregnancy nor achieve adequate glycaemic control before conception, strategies are needed to improve access to these programs, and to maximize those interventions associated with improved pregnancy outcome, such as smoking cessation and folic acid use.

Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde.

Abstract: Oxidative stress is thought to play a major role in the pathogenesis of Alzheimer's disease (AD). Although there is strong post-mortem and experimental evidence of oxidative damage occurring in AD brains, the use of markers in the peripheral circulation to show oxidative stress is less convincing. We examined plasma from AD patients for markers of increased oxidative stress. We report elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients compared to controls (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 micomol/l, respectively; p=0.001) but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 micromol/l; p<0.05). Levels of 4-HNE in AD patients were inversely related to ascorbate (r=-0.337; p=0.07) and Folstein Mini-Mental State Examination (MMSE) (r=-0.474; p=0.015). The concentration of protein sulphydryls, free-radical scavengers, was directly related to the MMSE result (r=0.427; p=0.03). Increased production of 4-HNE indicates increased oxidative stress (lipid peroxidation), which is not evident using the more common marker MDA. This elevation of 4-HNE was related to the degree of cognitive impairment (MMSE).

Maternal and neonatal outcomes in pregestational and gestational diabetes mellitus, and the influence of maternal obesity and weight gain: the DEPOSIT study

Abstract: We prospectively studied pregnancy outcome in 428 women with gestational diabetes mellitus (DM) and 196 women with pregestational DM, with particular reference to the influence of maternal obesity and excessive weight gain. These were consecutive singleton pregnancies delivered in our institution over 5 years. After controlling for multiple risk factors, including maternal BMI and pregnancy weight gain, women with pregestational DM were at increased risk (compared to those with gestational DM) for Caesarean delivery (OR 3.6, 95%CI 2.3-5.6), shoulder dystocia or cephalopelvic disproportion (OR 2.2, 95%CI 1.3-3.6), and gestational hypertension or toxaemia (OR 3.0, 95%CI 1.7-5.4). The offspring of these women were also at increased risk for admission to the neonatal intensive care unit (OR 4.0, 95%CI 2.3-6.8), large-for-gestational-age birthweight (OR 3.5, 95%CI 2.2-5.6), and preterm birth before 37 weeks (OR 3.8, 95%CI 2.5-5.9). Maternal obesity, and, to a lesser degree, excessive weight gain, were also independent risk factors for all these adverse maternal and neonatal outcomes, regardless of the type of DM, except for shoulder dystocia/cephalopelvic disproportion.

Tea flavonoids and cardiovascular health

Abstract: Tea is rich in antioxidant polyphenols (catechins, flavonols, theaflavins and thearubigins). Epidemiological evidence relating regular consumption of tea or related polyphenols to CHD is equivocal. Catechins are absorbed from tea, but low plasma concentrations are attained. The bioavailability of theaflavins and thearubigins is unknown. Tea does not reduce blood pressure or plasma lipids in well-controlled human trials. Tea polyphenols inhibit LDL lipid peroxidation in vitro, but the effect ex vivo is small. The plasma antioxidant potential increases after drinking green but not black tea. Tea consumption tended to reduce the development of aortic atherosclerosis in rabbits. Tea polyphenols exert marked effects on cells, and inhibit neutrophil migration and inflammatory responses, sometimes at low concentrations. These diverging results suggest potential beneficial effects, but emphasize the need for good human trials of tea using early markers of CHD before firm conclusions can be drawn.

Cerebral infarction in chronic meningitis: a comparison of tuberculous meningitis and cryptococcal meningitis

Abstract: Twenty-eight patients with cerebral infarction secondary to chronic meningitis were retrospectively identified at our institution over a period of 5 years. They accounted for 47% (17/36) of tuberculous meningitis (TBM) and 32% (11/34) of cryptococcal meningitis cases. Single infarctions were found in 15 patients and multiple infarctions in 13. The distribution of single infarctions was: basal ganglia 7; internal capsule 3; thalamus 1; cerebellum 1; and cortical infarct 3. Therapeutic outcomes at 3 months were determined using a modified Barthel INDEX: At follow-up of 3 months or more, 10 had good outcomes while the other 18 had poor outcomes. The 18 with poor outcomes included six who died, and 12 who had severe neurological sequelae. TBM and cryptococcal meningitis shared similar clinical features, both being frequently associated with other neurological complications, including hydrocephalus, cranial nerve palsy, and seizures in our patients. However, extracranial involvement, such as spinal and pulmonary involvement, was more commonly found in TBM patients. Cerebral infarction can occur in both the acute stage and later stages of treatment. Mortality and morbidity are high, and early diagnosis and appropriate antimicrobial treatment are essential. If hydrocephalus is demonstrated, early ventricular decompression is needed to prevent further cerebral ischaemia.

Hypokalaemia and paralysis.

Abstract: It is not uncommon for patients to present to the emergency room with severe weakness and a markedly low plasma potassium concentration. We attempted to identify useful clues to the diagnosis of hypokalaemic periodic paralysis (HPP), because its acute treatment aims are unique. We retrospectively reviewed charts over a 10-year period: HPP was the initial diagnosis in 97 patients. Mean patient age was 29+/-1.1 and the male:female ratio was 77:20. When the final diagnosis was HPP (n=73), the acid-base state was normal, the urine K(+) concentration was low, and the transtubular K(+) concentration gradient (TTKG) was <3. In patients with thyrotoxic periodic paralysis (TPP) (n=39), hypokalaemia was very commonly accompanied by hypophosphataemia (1.9+/-0.1 mg/dl). A clinical diagnosis of sporadic periodic paralysis (SPP) was made if hyperthyroidism and a family history of HPP were both absent (n=29). One subgroup of patients with HPP had a severe degree of hypernatraemia (167+/-5.0 mmol/l, n=3). There were only two patients with familial periodic paralysis (FPP). In 24 patients, the initial diagnosis was HPP, but subsequent studies failed to confirm this diagnosis. Each of these patients had an acid-base disorder, a high rate of renal K(+) excretion in the presence of hypokalaemia, and a TTKG of close to 7. With respect to therapy, much less K(+) was given to patients with HPP, yet 1:3 subsequently had a plasma K(+) concentration that eventually exceeded 5.0 mmol/l. Using plasma acid-base status, phosphate and K(+) excretion parameters allows a presumptive diagnosis of HPP with more confidence in the emergency room.

A case ascertainment study of septic discitis: clinical, microbiological and radiological features.

Abstract: We studied the spectrum of septic discitis presenting to two busy district general hospitals over 2.5 years (November 1996 to April 1999), surveying the case notes of all patients attending Royal Bournemouth and Poole Hospitals with probable septic discitis on magnetic resonance imaging (MRI). Twenty-two cases of septic discitis were identified, suggesting an annual incidence of 2/100 000/year. Seventy-three percent of patients were aged > or =65 years. In 91% of patients, back pain was the presenting symptom, with neurological signs evident in 45% of patients. Fever >37.5 degrees C was present in 68% of patients, and a marked elevation of erythrocyte sedimentation rate (ESR) in 91%. Diagnosis was originally by MRI in 86% of patients, with plain radiographs not diagnostic of discitis in the early stages of the infection. Staphylococcus aureus was the commonest pathogen (41%), but in 18% of patients, no organism was identified. The major predisposing factors to septic discitis were invasive procedures (41%), underlying cancer (25%) and diabetes (18%). Pre-existing degenerative spinal disease was found in 50% of patients. Four patients whose causative organism was not isolated had a poorer outcome: one death and three with increased morbidity. Our estimated incidence rate (2/100 000/year) is higher than that in previous studies and may be due to a higher detection rate with MRI and/or a genuine increase in the number of cases. Septic discitis should be considered in any patient who has severe localized pain at any spinal level, especially if accompanied by fever and elevated ESR, or in the immunosuppressed.

Adverse reactions to disease‐modifying anti‐rheumatic drugs in clinical practice

Abstract: We analysed computerized records of disease-modifying anti-rheumatic drug (DMARD) monotherapy to determine how long rheumatoid arthritis (RA) patients continued on five commonly prescribed DMARDs, and the incidence and time-course of adverse drug reactions (ADRs) they experienced. We studied the records for 3923 courses of DMARDs given to a cohort of 2170 patients monitored for a total of 9378 treatment-years. Methotrexate (MTX) was the DMARD most likely to be continued long-term; <45% of patients had discontinued the drug after 96 months. For the other DMARDs, the time until 50% discontinued due to ADRs or inefficacy was 43.3 months for sulphasalazine (SAS), 33.9 months for D-penicillamine (DPN) and 26 months for myocrisin. Most monitored ADRs requiring drug discontinuation were seen early in therapy, with a median time to onset of <6 months; the important exceptions to this were haematological ADRs to MTX, where the median delay to neutropenia was 16.9 months, and that to thrombocytopenia was 9.4 months. Monitored ADRs (identified by blood or urine tests) were seen least frequently with SAS (one ADR in every 35 patient-years of monitoring) but this apparent advantage was offset by a high incidence of gastrointestinal ADRs and inefficacy. Overall, one toxicity reaction requiring drug discontinuation was identified for every 15.9 patient-years of monitoring.

Paroxysmal atrial fibrillation

Abstract: There has been a tendency to treat paroxysmal atrial fibrillation (PAF) in a similar way to sustained AF, but treatment objectives may be very different. We discuss current definitions, epidemiology, pathophysiology and natural history of PAF, and review evidence for its treatment and management. PAF comprises between 25% and 62% of cases of AF, with similar underlying causes to those in sustained AF. The main objective of management is prevention of paroxysms and long-term maintenance of sinus rhythm, and Class 1c drugs are highly effective, although beta-blockers are useful alternatives. If patients have severe coronary artery disease or poor ventricular function, amiodarone is probably the drug of choice. Although randomized controlled trials of thromboprophylaxis in patients with paroxysmal AF per se are lacking, the approach to patients with paroxysmal AF should be similar to that in patients with sustained AF, with warfarin for 'high risk' patients and aspirin for those at 'low risk'. Non-pharmacological therapeutic options, including pacemakers, electrophysiological techniques and the implantable atrial defibrillator, show great promise. Despite paroxysmal AF being a common condition, management strategies are limited by evidence from small randomized trials, with inconsistencies over the definition of the arrhythmia and the inclusion of only symptomatic subjects. Evidence for antithrombotic therapy is also based on epidemiological studies and subgroup analyses of the large randomized trials.

The diagnosis of leprosy is delayed in the United Kingdom

Abstract: Diagnostic delay in leprosy can have serious neurological consequences for the patient. We studied the presentation of leprosy patients, focusing on delays in diagnosis, in a retrospective case-note review of 28 patients referred to The Hospital for Tropical Diseases during 1995-1998. The median ages at onset of symptoms and at diagnosis were 25.1 years (range 9-77.7) and 30.1 years (range 9-78.3), respectively. The median time from symptom onset to diagnosis was 1.8 years (0.2-15.2). Prior to referral to a leprologist, patients had seen a dermatologist (20), neurologist (9), orthopaedic surgeon (5) and rheumatologist (2). Delay in diagnosis occurred in 82% of cases. Misdiagnoses as dermatological and neurological conditions were important causes of delay, and 68% of patients had nerve damage resulting in disability. Leprosy can be difficult to diagnose outside endemic areas. Increased awareness amongst general practitioners and hospital specialists would lead to more rapid diagnosis, thus minimizing damage and disability.

Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects.

Abstract: Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTD). Homocysteine levels are elevated in mothers of NTD children, which may be due to decreased cellular vitamin B12 levels, as vitamin B12 is a cofactor for the methylation of homocysteine. Transcobalamin II (TC II) transports vitamin B12 to the tissues. To examine whether altered plasma transcobalamin levels are a risk factor for NTD, we determined the apo and holo form of TC II and haptocorrin (TCI+TCIII), vitamin B12 and homocysteine concentrations in the plasma of 46 mothers with NTD children, and in 73 female controls. Holo-tc II levels and holo-tc II percentages (holo-tc II/total tc II) in the first quartile of the control distribution were related to a three-fold (OR 2.9, 95%CI 0.9-9.2) and five-fold (OR 5.0, 95%CI 1.3-19.3) risk, respectively, for having a child with NTD, when compared with the last quartile. Homocysteine levels were significantly higher among individuals with low holo-tc II, low total vitamin B12 concentrations and low holo-tc II percentages. These low holo-tc II percentages are probably caused by reduced affinity of TC II for vitamin B12, which may be explained by genetic variation in the TC II gene. Vitamin B12 supplementation might therefore be warranted, in addition to folate, in the prevention of NTD.

Non-specialist management of acute renal failure.

Abstract: In a 12-month prospective study of the initial management of patients with acute renal failure (ARF) in East Kent (population 593 000), we evaluated the initial management of ARF and assessed what proportion of ARF may have been preventable. Patients were seen and assessed on a daily basis, and were followed until discharge from hospital or death; survivors were subsequently followed for 3 years. Overall, 288 patients developed ARF (486 per million population/year). Mean age at presentation was 73 years (range 14-96). Initial assessment was often suboptimal, and key features in investigation and initial management were often lacking. In 108 cases, ARF was iatrogenic and/or potentially preventable (53 preventable, 99 iatrogenic, 44 both). Overall survival was 56% at discharge from hospital, 35% at 1-year follow-up, 31% at 2 years, and 28% at 3 years. In discharged patients, recovery of function was complete in 69%. A significant proportion of ARF is preventable. Clear guidelines, easily accessible at the point of care, could aid the diagnostic evaluation of the patient with ARF and indicate where referral for a specialist opinion is appropriate.

Insulin lispro and regular insulin in pregnancy

Abstract: We assessed the safety of insulin lispro in gestational, type 1 and type 2 diabetes mellitus, analysing 635 pregnancies over a period of 7 years. We also evaluated patient satisfaction, sending an internationally‐accepted anonymous diabetes treatment satisfaction questionnaire to 22 patients (three type 1, 19 gestational diabetes) who received regular and lispro insulin in successve pregnancies. The success rate of pregnancies in women with gestational diabetes managed with diet alone ( n =325) was 99.3%. All 213 pregnancies in women with gestational diabetes requiring insulin were successful. There was no difference in maternal or fetal outcomes whether patients used regular insulin ( n =138) or insulin lispro ( n =75), but pre‐delivery HbA1c was lower with insulin lispro ( p <0.05). Pregnancy loss in patients with pre‐gestational diabetes (89 pregnancies in type 1 and eight in type 2 diabetes) was 18.6% for insulin and 3.7% for insulin lispro ( p =0.10). The incidences of congenital anomalies with regular insulin were 7.9% and 15.8% in gestational and pre‐gestational diabetes, respectively; the figures for insulin lispro were 6.6% ( p =0.79) and 3.8% ( p =0.16), respectively. Nineteen of the 22 surveyed patients completed the questionnaire. Satisfaction was higher with insulin lispro (26.3±2.3 vs. 18±8.9, p =0.0005). We found no increase in adverse outcome using lispro insulin in diabetic pregnancies, in either gestational or pre‐gestational diabetes. Patient satisfaction favoured insulin lispro. Several patients with type 1 diabetes who used regular insulin during pregnancy, chose lispro after delivery, but all who used lispro in pregnancy preferred to continue.

Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148.

Abstract: Familial Mediterranean fever (FMF) is caused by more than 25 mutations in the gene MEFV , which encodes pyrin (marenostrin), a protein implicated in the regulation of neutrophil activity. Pyrin Q148, is one of the five most common variants in populations in which FMF typically occurs. Our identification of the pyrin Q148 allele in several patients from ethnic groups in which FMF is not classically recognized who had longstanding fevers or AA amyloidosis prompted us to study the prevalence of pyrin Q148 in healthy British, Indian and Chinese subjects. The gene frequency was also sought in 50 British Caucasian patients with inflammatory arthritis, 25 of whom had AA amyloidosis, five Punjabi Indians with AA amyloidosis complicating inflammatory arthritis, and seven British Caucasian patients with uncharacterized longstanding fever syndromes. The allele frequency for pyrin Q148 was 21%, 15% and 0%, respectively, among Punjabi Indian, Chinese and Caucasian British controls, and was significantly increased among the patients with AA amyloidosis and the patients with obscure fever syndromes ( p <0.01). Pyrin Q148 is a polymorphism and occurs widely in global terms, and, although it may cause FMF when associated with certain other MEFV mutations, homozygosity for Q148 alone must usually be insufficient to produce FMF in the populations studied. The association of pyrin Q148 with AA amyloidosis and with obscure chronic inflammatory diseases suggests the variant may augment inflammation non‐specifically, which might have been beneficial during evolution, but could potentially exacerbate many chronic inflammatory disorders.

Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

Abstract: Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet.

Longitudinal surveillance of antibiotic use in the hospital.

Abstract: We evaluated antimicrobial use in our hospital by department, including indications for use, source of infections, use of the microbiology laboratory, and appropriateness of prescribing, in a prospective, comparative, non‐interventional study of all patients receiving antimicrobial agents. We excluded departments where antimicrobial use was negligible. The other 19 departments were followed for 3 ( n =4) or 4 ( n =15) months, including 2 consecutive months in the spring‐summer and either 1 or 2 in the autumn‐winter. Antimicrobial therapy was followed from initiation, through possible adaptations, and possible change from intravenous to oral therapy, until discontinuation of treatment. Overall, 6376 antibiotics were given to 2306 patients. Of the surveyed hospitalized patients, 62%±22% received antibiotics, with a range of 4–100% per department. Antibiotics were prescribed for infections acquired in the community (3037 instances, 47%), in the hospital (2182, 34%), in a nursing home (575, 9%), and for prophylaxis continued post‐operatively (582, 9%). The most common indications for antimicrobial use were: respiratory tract infection (1729, 27%), urinary tract infection (955, 15%), sepsis (701, 11%), intra‐abdominal infections (663, 10%), prophylaxis 582 (9%), soft‐tissue infection (572, 9%), and surgical site infection (319, 5%). Univariate indicators for appropriateness of treatment were: age, department, site of infection, source of infection, antimicrobial drug and serum creatinine (all p <0.001). Forty‐nine antimicrobials were prescribed in 279 combinations, 58% as single agent and 42% as drug combinations. Half of all antimicrobial use consisted of four agents: cefuroxime (19.1%), metronidazole (11.3%), gentamicin (10.6%) and ampicillin (10.2%), which together accounted for 20% of expenditure on antibiotics. Although use of as many as 53% of antimicrobials (26/49) surveyed was restricted, use in this category accounted for only 29% of all antimicrobial courses. Of 6376 antibiotic courses, 4101 (64%) were given intravenously and 2275 (36%) orally. Appropriateness of use of restricted drugs was lower (70%) than of unrestricted ones (84%, p <0.001). Of 24571 defined daily doses (DDD) given orally, 4587 (19%) were restricted, compared to 7264 (34%) of 21602 DDDs given intravenously ( p <0.001). Antibiotic treatment in our hospital appears to be substantial and increasing, justifying efforts to improve appropriateness of therapy and improve clinical and financial results.

Cardiovascular risk factors and the long‐term outcome of lupus nephritis

Abstract: We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11-67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.

Endemic strongyloidiasis on the Spanish Mediterranean coast.

Abstract: Diagnosis and treatment of Strongyloides stercoralis infection can be difficult, and a high degree of clinical suspicion in patients who have visited an endemic area is required. We describe the epidemiology and clinical features of 152 prospectively identified cases of strongyloidiasis in an European region, and identify risk factors for the development of severe forms of the disease. This was a prospective study of all patients admitted to a single institution over an 8‐year period. Patients ( n =152) were mainly elderly male farmers (79%) who had acquired the disease by working barefoot in contact with soil and ingesting non‐drinking water. Eosinophilia was a sensitive marker for the infection (82%). Twenty patients (13%) developed severe forms of the illness and six patients (4%) died. A significant association was found between severe forms of strongyloidiasis and steroid usage (OR 9.0, 95%CI 2.1–37.6), immunodebilitating illness (OR 10.1, 95%CI 3.2–32.3) and other immunosuppressive therapy (OR 13.7, 95%CI 2.9–58.7), but by logistic regression analysis, only immunodebilitating disease was as a risk factor (OR 2.1, 95%CI 1.78–2.43). S. stercolaris infection is endemic in the Spanish Mediterranean coast. The frequent development of severe forms of the disease, with a high mortality, makes early recognition and treatment essential.

Lung involvement and enzyme replacement therapy in Gaucher's disease

Abstract: Symptomatic lung involvement in Gaucher's disease is relatively rare, being restricted to patients with other severe manifestations. We describe our experience in eight of 411 patients in our referral clinic, who presented with prominent pulmonary signs or symptoms. There were four adults and four children; all have been successfully treated with enzyme replacement therapy. Routine means of monitoring pulmonary status including clinical assessment, chest X-ray, pulmonary function tests, and high-resolution CT (HRCT) were used. Enzyme treatment resulted in decreased hepatosplenomegaly, improved haematological parameters, and increased well-being; There was decreased clubbing and decreased dyspnoea in some of the patients, although on radiology, lung pathology had not normalized. All four children showed improved respiratory compliance, with significant improvement of the radiological findings in one and unchanged disease in the others. Two adults showed improvement in oxygen saturation but worsening of pulmonary hypertension. On chest X-ray, both had increased interstitial markings; one had gradual progression of pulmonary artery accentuation and fine interstitial stable pattern on HRCT. The other two adults had no change in lung function or on chest X-ray, but on HRCT there was apparent improvement in one patient. There is great heterogeneity in presentation and response to enzyme therapy in patients with Gaucher's disease and symptomatic lung involvement. Clinically, some benefited significantly from enzyme therapy, but in contrast to the dramatic reduction in organomegaly, there was no normalization in pulmonary function or lung architecture.

The critically ill: following your MEWS.

Abstract: A 62‐year‐old man with a chest infection is admitted to hospital as an emergency. For the following 5 days, he remains on a ward with a tachycardia of 120–130 bpm and respiratory rates in the mid 30s to low 40s. Despite supplemental oxygen, his recorded saturation often dips below 90%. Five days after admission, he becomes confused and then drowsy. At this time his systolic blood pressure falls below 80 mmHg. His urinary output is not recorded, although his creatinine increases over 6 days from 212 mmol/l at admission to 369 mmol/l. Doctors are concerned and make frequent visits, analyse several arterial blood gas samples and institute intermittent mask continuous positive airway pressure (CPAP) support. Six days after admission a registrar, not involved in the patient's care, notices from the end of the bed that the patient is moribund. The patient is admitted to the intensive care unit (ICU) and is intubated, ventilated and haemofiltered. The patient dies on the ICU 24 days later. This really happened, although some details have been changed to maintain patient confidentiality. Such patients are common on hospital wards across the UK. How do we know this? Because in our hospital, and in another 50 or more, intensive care outreach services (ICORS) have been established over the last year. Compared to patients admitted to ICU from theatres/recovery or the Accident and Emergency (A&E) department, those admitted from hospital wards have a higher percentage mortality (Figure 1).1 Indeed, about 30% of those admitted from a ward to the ICU have survived a cardiorespiratory arrest whilst in the ‘safety’ of a hospital ward. The median time these patients are in hospital before ICU admission is about 6 days. However, the longer the patient is in hospital before ICU admission, the higher their eventual hospital mortality. Some patients are referred to …

Long-term predictors of coronary artery disease and mortality in type 1 diabetes.

Abstract: We assessed clinical and biochemical predictors of death and/or cardiovascular disease in 147 type 1 diabetes mellitus (DM) patients followed-up for 14 years. At follow-up, 28 of patients (19%) had died, and 25 patients (18%) had developed or died of coronary artery disease (CAD). At baseline, those who died had significantly higher serum creatinine (p=0.001) and urine albumin/creatinine ratio (p=0.016), greater prevalence of retinopathy (p=0.006), lower serum apolipoprotein A1 (p=0.046), and lower daily insulin dose (p=0.024) than those who survived. CAD patients had a longer duration of diabetes (p<0.001), were older at the onset of diabetes and at presentation (p=0.001), and had higher prevalences of retinopathy (p=0.005) and neuropathy (p=0.016). The CAD group also had higher baseline serum creatinine (p=0.02), lower HDL cholesterol (p=0.004) and apolipoprotein A1 (p=0.007) and higher LDL cholesterol (p=0.028) and apolipoprotein B concentrations (p=0.027). Under logistic regression analysis (adjusted for age and sex), baseline urine albumin/creatinine ratio (p=0.003), presence of retinopathy (p=0.004), serum creatinine (p=0.028), and serum urea (p=0.034) were the most powerful predictors of mortality, while duration of diabetes (p<0.0001), baseline HDL cholesterol (p=0.012), serum creatinine (p=0.02), apolipoprotein B (p=0.038), LDL cholesterol (p=0.039), and systolic blood pressure (p=0.055) were the strongest predictors of CAD. These findings emphasize the role of abnormal lipoprotein metabolism in the development of CAD in type 1 DM. Indicators of renal impairment and the presence of retinopathy seem to be of greater importance in predicting overall mortality.

Helicobacter pylori--an African perspective.

Abstract: Summary Helicobacter pylori is ubiquitous in Africa, with acquisition in childhood the rule. Despite the prevalence of a virulent strain (in Soweto, most H. pylori organisms are cagA- and vacAS1-positive) H. pylori-associated pathology (duodenal ulcer, gastric ulcer and gastric cancer) has a variable, often low distribution in sub-Saharan Africa that does not parallel H. pylori prevalence in the population, suggesting a different natural history from that seen in developed countries. Progression to atrophic gastritis in Africans does not appear to differ from that reported in other regions, but as yet unidentified factors may play a role in inhibiting progression to gastric cancer. Studies have suggested that the specific IgG subclass response to H. pylori is predominately IgG1 (suggestive of a Th2 response), and the Th2 response may provide a protective effect against development of gastric cancer. Host immune mechanisms may be the key to different responses to H. pylori in the developed and developing worlds.

The diagnostic value of anti-neutrophil cytoplasmic antibody testing in a routine clinical setting

Abstract: Anti-neutrophil cytoplasmic antibody (ANCA) tests are a routine clinical assay in most UK hospitals. We examined the role of routine ANCA testing in achieving a diagnosis of systemic vasculitis in a routine clinical setting. From April 1996 to March 2000, 2734 samples from five hospital departments were tested for ANCA by indirect immunofluorescence (IIF) at a single laboratory. After April 1999, enzyme-linked immunosorbent assays (ELISAs) were performed on all IIF-positive samples. Clinical diagnosis was determined for all patients with a positive IIF ANCA, and a sample of the ANCA-negative patients. Some 2-18% of patients with suspected ANCA-associated systemic vasculitis (AASV) had positive IIF ANCA. The AASV diagnosis was confirmed in 0-56% of these cases. Analysis by department suggested that 88-100% of patients with a positive IIF ANCA did not have AASV, except in the Rheumatology department. The positive predictive value (PPV) of IIF ANCA for AASV was 59% and the negative predictive value (NPV) was 84%. Of the patients with proven AASV, 41% did not have ANCA on IIF. Combined ANCA testing by IIF/ELISA had a higher sensitivity and PPV but lower specificity than IIF alone for AASV. For the combined IIF/ELISA test, only the Rheumatology department had a sensitivity or PPV >0% for AASV. The PPV of ANCA by IIF/ELISA for AASV was 79% and the NPV was 63%. The ANCA test is being widely applied with very poor return. Guidelines for more effective usage are proposed.

Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action?

Abstract: The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Refsum's disease.

Abstract: Refsum's disease (hereditary motor and sensory neuropathy type IV) is a rare autosomal recessive condition first characterized by Sigvald Refsum in 1945. He initially chose the name heredoataxia hemeralopica polyneuritiformis,1 subsequently amending this to heredopathia atactica polyneuritiformis.2 Thankfully, the eponymous version now predominates in the literature, and these earlier terms have been largely abandoned. Refsum's disease is caused by defective alpha oxidation of phytanic acid (3,7,11,15 tetramethylhexadecanoic acid), a branched‐chain fatty acid present in a wide range of foodstuffs including dairy products, some meats and fish.3 The defective enzyme is phytanoyl‐coenzyme A hydroxylase, which normally catalyses the second step in the breakdown of phytanic to pristanic acid using the CoA derivative as a substrate (the first step in alpha oxidation is the conversion of phytanic acid to phytanoyl CoA by Phytanoyl CoA ligase).4 This results in accumulation of phytanic acid, with elevated levels in blood and other tissues including fat and neurons (Figure 1). Phytanic acid can also be catabolized from the non‐carboxyl end by omega oxidation, but the capacity of this pathway is severely limited to ∼10 mg of phytanic acid per day.5 The average diet contains ∼50 mg/day, and this factor, in combination with limited excretory mechanisms (via the kidneys and skin), leads to phytanic acid accumulation. The mechanism of phytanic acid toxicity is unclear, but it may be incorporated into tissue lipids and result in impaired myelin function. An alternative hypothesis is that excess levels affect the metabolism of fat‐soluble vitamins. Levy has suggested that high phytanic acid levels interfere with vitamin A esterification in the retinal pigment epithelium leading to the production of a toxic substance and progressive visual failure.6 The physiological role of phytanic acid is unknown. Figure 1. The biochemistry of Refsum's disease. The onset of symptoms is typically in late childhood or …

Ethnic differences in hypertension and blood pressure control in the UK

Abstract: Hypertension is a major risk factor for cardiovascular and cerebrovascular disease, the major causes of death in the UK and other Western countries. Despite this, many patients with hypertension remain undetected and inadequately treated. In order to accurately assess the effectiveness of health programmes aimed at hypertension, it is important first, to establish the mean blood pressure (BP) levels and the prevalence of hypertension in a population, particularly amongst the different ethnic groups, and second, to determine the proportion of people achieving adequate BP control (defined as BP <140/95 mmHg) on anti‐hypertensive medication, given the risk of cardiovascular mortality and morbidity associated with high blood pressure. Nevertheless, the epidemiological data on ethnic differences in BP and hypertension prevalence in the UK are conflicting. Detection, treatment, and control of hypertension among the three main ethnic groups in the UK is important, given that recent studies indicate substantial ethnic differences in cardiovascular mortality.1 For example, compared to Caucasians, Afro‐Caribbeans and people of African descent have a higher incidence of stroke2 and end‐stage renal failure,3 whereas coronary artery disease is less common. Conversely, South‐Asians (defined as people originating from the Indian subcontinent and East Africa) have a higher incidence of coronary heart disease.2 With advancing age, the prevalence of hypertension increases. In the Health Survey for England, for example, the prevalence of hypertension was 3.3% in those aged 140 mmHg (systolic) and/or 90 mmHg (diastolic), is a common problem.4 Several population‐based studies in …

The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred

Abstract: The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disease characterized by the occurrence of parathyroid tumours and fibro-osseous tumours of the jaw bones. Some HPT-JT patients may also develop renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease. The HPT-JT gene has been mapped to chromosome 1q25-q31, and we report the clinical and genetic findings in a kindred from central Portugal. HPT-JT was observed in six members from three generations; all had primary hyperparathyroidism (five had parathyroid adenomas, one a parathyroid carcinoma). Ossifying jaw fibromas affecting the maxilla and/or mandible were observed in 5/6. Renal cysts (<2.5 cm) were observed in four. Genetic studies using 18 polymorphic loci from chromosome 1q25-q31, together with leukocyte DNA from 11 family members and tumour DNA from three parathyroids (two adenomas and one carcinoma), revealed loss of tumour heterozygosity in the parathyroid carcinoma only, and the retained haplotype was found to cosegregate with the disease in the six affected members. A new Portuguese kindred with the HPT-JT syndrome that maps to chromosome 1q25-q31 has been identified, and these findings will help in the further characterization of this inherited disorder.

Renal complications of jejuno-ileal bypass for obesity.

Abstract: Jejuno-ileal bypass has until recently been an accepted treatment for refractory morbid obesity. Although hyperoxaluria causing renal tract calculi is a well-recognized complication, we describe eight patients who developed significant renal failure attributable to hyperoxaluria resulting from this procedure, three requiring renal replacement therapy. We review the literature, describing 18 other cases with renal failure, the mechanisms of hyperoxaluria and its treatment. Because reversal of the bypass may result in stabilization or partial improvement of renal function, these patients require long-term follow-up of renal function.

Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis

Abstract: Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA. Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count 70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07+/-0.1x10(9)/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs. 11.6+/-5; 7.5+/-3.8 days vs. 12+/-4.5; and 7.3+/-4.8 days vs. 13+/-6.1, respectively (all p<0.05). G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.