QJM - recent issues

Elements: in this month's issue

Bannon, M. — Fri, 23 Oct 2009 04:10:33 PDT

Genetics and the general physician: insights, applications and future challenges

Knight, J.C. — Fri, 23 Oct 2009 04:10:33 PDT

Scientific and technological advances in our understanding of the nature and consequences of human genetic variation are now allowing genetic determinants of susceptibility to common multifactorial diseases to be defined, as well as our individual response to therapy. I review how genome-wide association studies are robustly identifying new disease susceptibility loci, providing insights into disease pathogenesis and potential targets for drug therapy. Some of the remarkable advances being made using current genetic approaches in Crohn's disease, coronary artery disease and atrial fibrillation are described, together with examples from malaria, HIV/AIDS, asthma, prostate cancer and venous thrombosis which illustrate important principles underpinning this field of research. The limitations of current approaches are also noted, highlighting how much of the genetic risk remains unexplained and resolving specific functional variants difficult. There is a need to more clearly understand the significance of rare variants and structural genomic variation in common disease, as well as epigenetic mechanisms. Specific examples from pharmacogenomics are described including warfarin dosage and prediction of abacavir hypersensitivity that illustrate how in some cases such knowledge is already impacting on clinical practice, while in others prospective evaluation of clinical utility and cost-effectiveness is required to define opportunities for personalized medicine. There is also a need for a broader debate about the ethical implications of current advances in genetics for medicine and society.

A multi-centre survey of inpatient pharmacological management strategies for alcohol withdrawal

Ward, D., Murch, N., Agarwal, G., Bell, D. — Fri, 23 Oct 2009 04:10:33 PDT

Background: It is well recognized that alcohol is a growing problem in the UK with significant morbidity and mortality and associated resource implications for the National Health Service (NHS). The inpatient management of alcohol withdrawal is felt to be variable between hospitals. The aim of this study was to assess the variation in pharmacological management and acute inpatient alcohol services across NHS hospitals in the UK.

Method: A web-based survey was distributed to Society for Acute Medicine (SAM) members and others with an interest in Acute Medicine between January and March 2008.

Results: The results suggest poor utilization of guidelines, variable drug regimens and differences in acute alcohol-related support services.

Conclusion: In response to these findings, we suggest that a simplified national approach is required for what is now recognized to be an epidemic problem.

Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series

MacConnachie, A.A., Fox, R., Kennedy, D.R., Seaton, R.A. — Fri, 23 Oct 2009 04:10:33 PDT

Background: Clostridium difficile-associated diarrhoea (CDAD) is an increasingly common and life threatening consequence of modern medical practice. Recurrent disease is seen in up to one-third of patients and there is no consensus on optimal therapy. Restoration of normal colonic flora addresses the underlying pathogenic mechanism in CDAD.

Methods: We describe the use of nasogastrically administered faecal transplant in the treatment of 15 patients with recurrent CDAD. Retrospective case note review was used to review the success and safety of therapy.

Results: Of 15 patients treated using this technique, 11 were cured of CDAD. Two patients required a further course of metronidazole after transplantation and one patient required a second treatment. One patient had recurrence of CDAD 4 weeks after treatment following a course of broad-spectrum antibiotics. No adverse events were noted.

Conclusion: In our experience, this technique is an effective and safe treatment for recurrent CDAD. Faecal transplantation via a nasogastric tube could be considered in patients with refractory relapsing CDAD.

Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos

Fri, 23 Oct 2009 04:10:33 PDT

Background: Many organophosphorus (OP) insecticides have either two O-methyl or two O-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures.

Aim: We aimed to describe the clinical course and responsiveness to therapy of people poisoned with two S-alkyl OP insecticides—profenofos and prothiofos.

Design: We set up a prospective cohort of patients with acute profenofos or prothiofos self-poisoning admitted to acute medical wards in two Sri Lankan district hospitals. Clinical observation was carried out throughout their inpatient stay; blood samples were taken in a subgroup for assay of cholinesterases and insecticide.

Results: Ninety-five patients poisoned with profenofos and 12 with prothiofos were recruited over 5 years. Median time to admission was 4 (IQR 3–7) h. Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9–20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2–38). Thirteen patients poisoned with profenofos required intubation for respiratory failure (13/95; 13.7%, 95% CI 7.5–22); two prothiofos-poisoned patients required intubation. Both intubations and death occurred late compared with other OP insecticides. Prolonged ventilation was needed in those who survived—a median of 310 (IQR 154–349) h. Unexpectedly, red cell AChE activity on admission did not correlate with clinical severity—all patients had severe AChE inhibition (about 1% of normal) but most had only mild cholinergic features, were conscious, and did not require ventilatory support.

Conclusions: Compared with other commonly used OP insecticides, profenofos and prothiofos are of moderately severe toxicity, causing relatively delayed respiratory failure and death. There was no apparent response to oxime therapy. The lack of correlation between red cell AChE activity and clinical features suggests that this parameter may not always be a useful marker of synaptic AChE activity and severity after OP pesticide poisoning.

Clinical phenotype of cystic fibrosis patients with the G551D mutation

Fri, 23 Oct 2009 04:10:33 PDT

Background: Data on whether the phenotype of cystic fibrosis (CF) patients with compound heterozygocity for G551D (Gly551Asp) differs from patients with F508del (Phe508del) homozygous mutations is divergent.

Aim: We hypothesized that CF patients with the G551D mutation would have less severe disease than F508del homozygotes.

Design: We compared the clinical phenotype of adult patients with a G551D mutation with adult patients homozygous for F508del and those with the missense mutation R117H (Arg117His). Compound heterozygotes for the G551D and R117H were analysed separately.

Methods: Data were collected for 101 adult CF patients. Group 1–4 represents in order F508del homozygote patients (n = 61), those with the G551D mutation and a more severe mutation (n = 13), those with R117H mutation and a more severe mutation (n = 23) and also those compound for both the R117H and G551D mutations (n = 4).

Results: Our findings have shown that adult patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous adult patients. Higher FEV₁ and body mass index and less impaired glucose tolerance was demonstrated in the patients with G551D and R117H compared to F508del homozygotes. There was a reduced yearly rate of decline of FEV₁ (P < 0.05), infection with Pseudomonas aeruginosa along with reduced burden of care. Compound heterozygosity for G551D and R117H mutations was associated with normal spirometry, body mass index, no chronic infection and no symptoms.

Conclusions: Mutations on different chromosomes are not independent of each other for the overall impact on the amount of functional CFTR. This study suggests that patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous patients, but the phenotype is not as mild as patients with the R117H mutation.

Early onset type 2 diabetes mellitus: a harbinger for complications in later years--clinical observation from a secondary care cohort

Song, S.H., Hardisty, C.A. — Fri, 23 Oct 2009 04:10:33 PDT

Background: Little is known about the complication burden in later years among early onset type 2 diabetes mellitus (T2DM).

Aim: To determine the magnitude of diabetes complications and adequacy of risk factor management and to test the hypothesis that diabetes duration is an important contributing factor to these complications.

Design: A cross-sectional study of secondary care diabetes population.

Methods: Data on glycaemic control, cardiovascular risk factors (overweight/obesity, hypertension, dyslipidaemia), cardiovascular disease (CVD) and microvascular complications among those diagnosed before (early onset) and after (later onset) 40 years of age at different diabetes durations (<10, 10–20 and >20 years) were analysed.

Results: A total of 2733 subjects were identified, of which 527 had diabetes diagnosed below the age of 40 years. By the sixth decade of life, early onset cohort experienced high complication burden (CVD: 37.2%, retinopathy: 59.3% and neuropathy: 53.1%). Complication prevalence increased with diabetes duration but the increment rate was greater among early onset cohort. Compared with those diagnosed after 40, early onset cohort experienced similar burden of microvascular complications ~13–20 years earlier. Diabetes duration was a significant predictor for microvascular and CVD complications. Prevalence of CVD risk factors was high (~80–93%) regardless of the age of diagnosis and diabetes duration. Early onset subjects were more likely to have poorer glucose control (~70–78%), untreated hypertension (26.3%) and a substantial number did not receive statin treatment for primary prevention (34.8%).

Discussion: Early onset T2DM subjects are at substantial risk of developing diabetes complications in later years but at an earlier stage than later onset cohort and prolonged exposure to adverse diabetic milieu is an important contributing factor. Management of risk factors for diabetes complications was inadequate among early onset subjects.

The nervous heart: a case report and discussion of an under-recognized clinical problem

Agarwal, S., Lyon, A., Nachev, P., Everitt, A. — Fri, 23 Oct 2009 04:10:33 PDT

Severe back pain in a hemodialysis patient

Hsiao, P.-J., Diang, L.-K., Lin, S.-H., Wang, C.-W. — Fri, 23 Oct 2009 04:10:33 PDT

Haemorrhagic cardiac tamponade: a rare complication of pneumonia

Natarajan, B., Stephens, J.W. — Fri, 23 Oct 2009 04:10:33 PDT

Small bowel volvulus and the whirl sign

Lin, C.-H., Kao, P.-C., Wang, H.-P., Lien, W.-C. — Fri, 23 Oct 2009 04:10:33 PDT

Primary prevention of cardiovascular disease with statins: cautionary notes

Goldstein, M.R., Mascitelli, L., Pezzetta, F. — Fri, 23 Oct 2009 04:10:33 PDT

Embolic complication of Tako-Tsubo cardiomyopathy

Figueredo, V.M., Gupta, S. — Fri, 23 Oct 2009 04:10:34 PDT

Profound hypokalaemia mimicking acute myocardial infarction

Dalzell, J.R., Jackson, C.E., Petrie, M.C. — Fri, 23 Oct 2009 04:10:34 PDT

The Regent Park's three royal medical colleges

James, D. G. — Fri, 23 Oct 2009 04:10:34 PDT

Oh no--it's Donald Hunter!

Seaton, A. — Fri, 23 Oct 2009 04:10:34 PDT

Elements: In this month's issue

Bannon, M. — Wed, 23 Sep 2009 06:43:26 PDT

Q fever: persistence of antigenic non-viable cell residues of Coxiella burnetii in the host--implications for post Q fever infection fatigue syndrome and other chronic sequelae

Wed, 23 Sep 2009 06:43:26 PDT

Background: Our previous studies of persistence of Coxiella burnetii in humans after an initial acute Q fever infection revealed raised, maintained antibody levels and low levels of coxiella genomic DNA at the age of 5 years from onset in Australian patients and at 12 years in patients in the 1989 Birmingham UK Q fever outbreak. Attempts to isolate the coxiella in standard cell culture and susceptible mice by serial passage of PCR positive PBMC and bone marrow were negative.

Aim: To retest PCR positive patient samples by more sensitive methods for viable coxiellas and for the coxiella cell components of antigen and specific lipopolysaccharide (LPS). To re-interpret the previous results in the light of the new information. To review the pertinent literature for a concept of an immuno-modulatory complex generated by the current studies.

Design: Laboratory case study.

Methods: Stored patient samples were inoculated into SCID mice that were followed for 60 days. Mouse spleen and liver samples were then examined by PCR assay for targets in the COM1 and IS1111a sequences and for antigens by IFA with a polyclonal rabbit antiserum to C. burnetii Phase 1 and a monoclonal antiserum to Phase 1 LPS (details; O. Sukocheva et al., unpublished data).

Results: All specimens, including a recently excised heart valve from a Birmingham patient with late developing endocarditis, were infection negative in SCID mice. Dilutions of SCID mouse spleen and liver homogenates titrated in PCR assays were negative at dilutions attained by control mice inoculated with an endpoint dilution of a viable prototype strain of C. burnetii. Sections of the spleens from all specimens showed a complex of coxiella antigen-LPS by IFA.

Discussion/Review: We advance a concept of long-term persistence of a non-infective, non-biodegraded complex of coxiella cell components with its antigens and specific LPS [so called Immunomodulatory complex (IMC)] associated with traces of genomic DNA that signalled its presence in our earlier studies. The IMC's survival in patients for at least 12 years, and in one patient for 70 years implies a capacity for serial passage in macrophages with effective down-regulation of their biodegrading functions. The review assesses the compatibility of the IMC concept in relation to cogent literature on C. burnetii interactions with macrophage and cell-mediated immunity. Some remaining gaps in our knowledge of the organ sites and duration of carriage of viable coxiellas after initial infection are also identified.

New developments in the management of malaria in adults

Roe, J.K., Pasvol, G. — Wed, 23 Sep 2009 06:43:26 PDT

In dealing with malaria, the challenge that remains is prompt diagnosis and initiation of specific and supportive treatment. Physicians should be aware of the therapeutic and prognostic implications of life-threatening falciparum vs. non-falciparum malaria and be able to at least recognize the severe manifestations of malaria which may require an increased level of care or referral to a specialist unit. The most important new developments in managing malaria in patients are the increasing problem of drug resistance, the availability of new antimalarial agents (most notably the artemisinins) and general advances in the management of any acutely ill patient in critical care.

Progression of cardiac dysfunction in patients with atherosclerotic renovascular disease

Wed, 23 Sep 2009 06:43:27 PDT

Background: Patients with atherosclerotic renovascular disease (ARVD) are at increased risk of heart disease because of the association with hypertension, coronary artery disease, cardiac failure and chronic kidney disease (CKD). A previous echocardiographic cross-sectional study showed that only 5% of patients with ARVD had normal cardiac structure and function at baseline. In this longitudinal study of the same patient cohort the progression of cardiac dysfunction and factors which predict declining cardiac function in patients with ARVD were delineated.

Methods: Seventy-nine patients were available for baseline analysis, but 16 withdrew from follow-up during the study. Forty-three patients (27M and 16F, age at study entry [mean ± SD] 69.7 ± 8.0 years) who were managed conservatively and 8 (age 69.8 ± 5.7) who were managed with renal revascularization underwent echocardiography and 24 h ambulatory blood pressure investigations at baseline and 12 months thereafter. The two data sets were interrogated to determine changes in blood pressure and cardiac status (morphological and functional); baseline factors which predicted such changes were ascertained. Twelve patients underwent baseline investigation but did not complete follow-up because of death (nine patients) or requirement of dialysis (three patients).

Results: Conservatively managed patients: At 12 months eGFR, (38.6 ± 18.3 vs 35.0 ± 18.5 ml/min; P = 0.001) had fallen whilst proteinuria had increased (0.3 ± 0.4 vs 0.6 ± 0.8 g/24 h; P = 0.001). Despite no increase in the number of blood pressure medications there was a fall in blood pressure between baseline and follow-up investigations (140.0 ± 16.5/75.3 ± 11.8, MAP 98.6 ± 12.3 mmHg vs 135.7 ± 16.1/69.6 ± 9.1, MAP 92.5 ± 10.2 mmHg; P < 0.001 for diastolic blood pressure and MAP). At 12 months, there was an increase in the number of patients with LVH (72.9% vs 81.4%). There were increases in left ventricular dimensions [left ventricular end diastolic diameter (5.1 ± 0.8 vs 5.5 ± 0.8 cm; P = 0.009), and left ventricular end diastolic volume (140.9 ± 39.5 vs 163.3 ± 61.0 ml; P = 0.01)]. There was no significant relationship of these changes in cardiac parameters to anatomical severity of renal artery disease but patients with severe renal dysfunction at baseline had an increase in left ventricular dilatation at follow-up. Linear regression analysis revealed an association between elevated time-averaged PTH and LV dilatation [β-coefficient and 95% confidence intervals, 0.18 (0.04, 0.32); P = 0.01]. Revascularization: No significant changes in any biochemical or echocardiographic parameters were seen between baseline and 1 year investigations in this small sub-group.

Conclusion: Patients with ARVD exhibit a high prevalence of LVH at diagnosis and progressive left ventricular dilatation over the first year after diagnosis. This dilatation is associated with severe renal impairment at baseline and not associated with anatomical severity of renal artery disease.

Prehypertension is associated with insulin resistance

Hwu, C.-M., Liou, T.-L., Hsiao, L.-C., Lin, M.-W. — Wed, 23 Sep 2009 06:43:27 PDT

Background: Prehypertension, a new category of blood pressure (BP) classification introduced by The Seven Report of the Joint National Commission (JNC-7) on High BP for individuals with systolic BP in the range of 120–139 mmHg or diastolic BP between 80 and 89 mmHg, is a strong predictor for the development of hypertension. Insulin resistance (IR) has been proposed to be a key feature of metabolic abnormalities of hypertension and may precede the elevation of BP.

Aim: The purpose of the study is to evaluate whether prehypertension is associated with IR.

Design: This is a cross-sectional study.

Methods: Anthropometric and BP measurements were performed in 83 prehypertensive subjects and 192 normotensives. All subjects received a 75-g oral glucose tolerance test (OGTT) for the measurements of IR.

Results: The prehypertensive subjects were more obese and had higher levels of fasting triglycerides and 2-h insulin than the normotensives. The subjects with prehypertension were more insulin resistant than the counterparts, indicated by lower insulin sensitivity index, ISI_0,120, values. While there was no difference between the two groups in insulin response of OGTT after adjustments for confounders, the prehypertension group maintained significant between-group differences in glucose response even when the incremental insulin levels were added to covariates for adjustments.

Discussion: Our data show that prehypertension is associated with IR. The subjects with prehypertension have clinical characteristics of the IR syndrome. It seems that the prehypertension group cannot handle oral glucose challenge as well as the normotension, probably a consequence of IR in prehypertension.

Globalization, immigration and diabetes self-management: an empirical study amongst immigrants with type 2 diabetes mellitus in Ireland

Thabit, H., Shah, S., Nash, M., Brema, I., Nolan, J.J., Martin, G. — Wed, 23 Sep 2009 06:43:27 PDT

Background: We have previously reported that immigrants in Ireland have poorer glycemic control compared with a matched population of Irish patients. This may be associated with poor diabetes self-care and low health literacy.

Aim: To compare the diabetes self-care profile of non-Irish-national patients i.e. immigrant patients (IM) and Irish patients (IR) attending a hospital diabetes clinic and to evaluate differences in health literacy between the two cohorts.

Methods: We studied the differences in diabetes self-management between 52 randomly selected non-Irish-national patients with type 2 diabetes and 48 randomly selected Irish/Caucasian patients. Rapid Estimate of Adult Literacy in Medicine (REALM) was used to assess health literacy.

Results: IM had poorer glycemic control than IR (HbA1c 8.0 ± 1.9 vs. 6.9 ± 1.4%, P < 0.005). A significant proportion of IM forget to monitor their daily blood glucose (42.1% vs. 12.5%, P < 0.05). Family support is more important amongst IM in performing daily blood glucose monitoring (75% vs. 47.7%, P < 0.05), taking medications (81.7% vs. 42.2%, P = 0.01) and following an appropriate meal plan (87.6% vs. 62.2%, P < 0.05). Fifty-three percent can only understand simple or familiar questions about their diabetes care; 65.9% can only provide information on simple or familiar topics about their diabetes. Health literacy was found to be lower in the IM groups when assessed using REALM (52.7 vs. 61.4, P = 0.01).

Conclusion: Those providing diabetes education and care need to be aware of differing patient expectations regarding family involvement in the care of their diabetes and the possible contribution of language problems and lower health literacy to a limited understanding of diabetes self-care.

Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning

Bradberry, S., Sheehan, T., Vale, A. — Wed, 23 Sep 2009 06:43:27 PDT

Background: Chelation therapy has been used as a means of reducing the body burden of lead for five decades. Intravenous sodium calcium edetate has been the preferred agent, but there is increasing evidence that dimercaptosuccinic acid (DMSA) is also a potent chelator of lead.

Methods: Oral DMSA 30 mg/kg/day was administered to adults with blood lead concentrations >= 50 µg/dl. The impact of DMSA on urine lead excretion, on blood lead concentrations and on symptoms was observed. The incidence and severity of adverse effects was also recorded.

Results: Thirty-five courses were given to 17 patients. DMSA significantly (P < 0.0001) increased urine lead excretion and significantly (P < 0.0001) reduced blood lead concentrations. Mean daily urine lead excretion exceeded the pre-treatment value by a median of 12-fold with wide variation in response (IQR 8.9–14.8, 95% CI 10.1–14.6). Pre-treatment blood lead concentrations correlated well with 5-day urine lead excretion. Headache, lethargy and constipation improved or resolved in over half the patients within the first 2 days of chelation. DMSA was generally well tolerated, but one course was discontinued due to a severe mucocutaneous reaction. There was a transient increase in alanine aminotransferase (ALT) activity during 14% of chelations. DMSA caused a significant increase in urine copper (P < 0.0001) and zinc (P < 0.05) excretion.

Conclusion: Oral DMSA 30 mg/kg/day is an effective antidote for lead poisoning, though there is a wide inter- and intra-individual variation in response.

Bilateral neck paragangliomas

Mumoli, N., Cei, M., Pauletti, M., Ferrito, G., Scazzeri, F. — Wed, 23 Sep 2009 06:43:27 PDT

Paragangliomas of the head and neck are rare neoplasms presented as cervical mass, generally bilateral, that arise from chemoreceptors located at the carotid bifurcation (carotid body tumors), along the vagus nerve (vagal paragangliomas), and in the jugular fossa and tympanic cavity (jugulotympanic paragangliomas). They are typically asymptomatic at the beginning, highly vascular, slow-growing and compressing the surrounding anatomic structures. Only radical surgery is the curative treatment for paragangliomas. We present a case of a 62- year-old woman with a diagnosis of bilateral neck paragangliomas where surgical removal was judged burdened by excessive risk because of the size of the tumor

A case of ST-elevation and nystagmus--when coronary thrombosis is not to blame

Daly, M.J., Dixon, L.J. — Wed, 23 Sep 2009 06:43:27 PDT

We present the case of a post-menopausal female who, following a prolonged period of vomiting and diarrhoea, presented acutely with Wernicke's; encephalopathy, chest pain, ST-segment elevation and congestive cardiac failure associated with hypotension. Coronary angiography demonstrated no abnormality. Haemodynamics improved significantly in the short-term following intravenous thiamine replacement, with complete resolution of all ST-segment abnormalities and normalization of left ventricular function at six-week follow-up. Shoshin beriberi in the context of metabolic alkalosis, secondary to severe electrolyte depletion, is exceptional and is a differential diagnosis to be considered in all malnourished patients presenting with symptoms and signs suggestive of an acute coronary syndrome, especially those with a history of alcohol-dependence.

Isolated pulmonary Langerhans cell histiocytosis

Kasmani, R., Narwal-Chadha, R., Naveed, S., Sahoo, D. — Wed, 23 Sep 2009 06:43:27 PDT

The enigma of pulmonary hypertension after splenectomy--does the megakaryocyte provide a clue?

Thachil, J. — Wed, 23 Sep 2009 06:43:27 PDT

Pulmonary hypertension is a common and debilitating condition which is increasingly being recognized in haematological patients. This is particularly so in haemolytic diseases like thalassaemia and myeloproliferative conditions like idiopathic myelofibrosis. Recently, splenectomy, which may be required for some of these conditions, have been linked to this complication although the exact pathophysiology is still not established. The manuscript explains the role of the less recognized ‘lung megakaryocytes’ in the development of this complication.

The limitations of routine total digoxin immunoassay in patients with advanced chronic kidney disease

Sharma, R., Guy, M., Rudenski, A., Lamerton, E., Kalra, P.A. — Wed, 23 Sep 2009 06:43:27 PDT

History of the cholesterol hypothesis in Britain

Thompson, G. — Wed, 23 Sep 2009 06:43:27 PDT

Variability in the prevalence of radiographic stigmata and in their use for profiling disease severity makes comparisons more complicated

Jolobe, O. — Wed, 23 Sep 2009 06:43:27 PDT

Lunch with Richard Asher

Seaton, A. — Wed, 23 Sep 2009 06:43:27 PDT

Elements: In this month's issue

Bannon, M. — Wed, 19 Aug 2009 06:52:14 PDT

Commissioned article: management of exotic snakebites

Warrell, D.A. — Wed, 19 Aug 2009 06:52:14 PDT

Exotic (foreign or non-native) snakes, including venomous species, are becoming increasingly popular pets in Western countries. Some of them are kept illegally (as defined by the UK Dangerous Wild Animals Act of 1976). There is a large international market for such animals, with contraventions of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). In the UK, several other European countries and the USA the reported numbers of bites by venomous exotic snakes, although small, are increasing but still underestimate the occurrence of these occasionally fatal events because of the victims’ reluctance to seek medical care. Victims are predominantly young men who have been drinking alcohol. Bites may be intentionally provoked. In Europe, the species most often involved are cobras, green mambas, American pit vipers particularly rattlesnakes, African adders, vipers and Asian green pit vipers. To illustrate the special problems involved, case histories are presented of bites by exotic species in the UK and of bites abroad, where patients were repatriated for treatment. In view of the relative rarity and diversity of these cases, expert advice must usually be sought. These requests should include information about the species thought to have been responsible and the history and timing of the evolution of envenoming. Sources of advice and antivenom are discussed together with recommendations for appropriate first aid and emergency treatment while this is being awaited. Respiratory and cardiovascular resuscitation may be required and when systemic or severe local envenoming develops, specific (equine or ovine) antivenom is indicated.

Nocturnal hypoglycaemia in type 1 diabetes--frequency and predictive factors

Woodward, A., Weston, P., Casson, I.F., Gill, G.V. — Wed, 19 Aug 2009 06:52:14 PDT

Background: Nocturnal hypoglycaemia (NH) remains a problem in type 1 diabetes and spontaneous asymptomatic NH may be a risk factor for sudden death (‘Dead in Bed’ syndrome).

Aims: To explore whether any predictive relationship exists between the average or time-specific glycaemia and the occurrence of NH.

Methods: Twenty-five healthy patients with type 1 diabetes underwent two separate overnight periods of continuous glucose monitoring (CGM) using a MMT-7002 Medtronic MiniMed System. There was a 6-week interval before the second monitoring period. CGM glucose levels recorded between 23:00 and 08:00 h defined the nocturnal period and recorded glucose monitoring levels <3.5 mmol/l for at least 10 min during this time-defined NH. A CGM recording at 23:00 h and 08:00 h were taken as the bedtime and fasting glucose levels, respectively.

Results: The mean ± SD age was 37 ± 7 years and duration of diabetes 13 ± 7 years; 16 (64%) were on long-acting analogue insulin. Forty-nine CGM data sets were recorded. Fourteen episodes of NH occurred in 12 patients (Group 1), 13 patients (Group 2) had no NH. Group 1 (NH) had a lower mean bedtime glucose recorded compared with Group 2 (7.7 ± 4.3 vs. 11.4 ± 4.0 mmol/l, P = 0.0035). Fasting glucose level was also lower in Group 1 following the occurrence of NH (P = 0.014). There was no difference in the type of insulin used between the two groups.

Conclusions: Our data show that in normal day to day settings, NH is common and that the bedtime glucose level is a significant predictive factor.

Resistance exercise plus to aerobic activities is associated with better lipids' profile among healthy individuals: the ATTICA study

Wed, 19 Aug 2009 06:52:14 PDT

Background: The influence of different types of exercise on risk factors for cardiovascular diseases has rarely been investigated. The aim of the present work was to evaluate the effect of adding resistance exercise to aerobic activities on lipid–lipoprotein profile, in a representative sample of men and women from the province of Attica, Greece.

Methods: We randomly enrolled 1514 and 1528 healthy men and women, respectively, stratified by city, age and gender distribution. Participants were classified as inactive (INA), sufficiently active (SA) and highly active for either aerobic activities (HAA) alone or a combination of aerobic plus resistance exercise (HAC). The main outcome measures are lipid–lipoprotein profile [total, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B] and anthropometric indices.

Results: From those participating in aerobic activities, 480 (31.7%) men and 502 (32.9%) women were classified as SA, 100 men (6.6%) and 93 women (6.1%) as HAA and 90 men (5.9%) and 49 women (3.2%) as HAC. After various adjustments were made, men from the HAC group had an average of 23% lower plasma triacylglycerol concentration (P = 0.04) and 10% lower LDL-cholesterol (P = 0.01) when compared with the HAA group. Moreover, women from the HAC group had 13% lower LDL-cholesterol when compared with HAA group (P = 0.051).

Conclusions: These data suggest that combining aerobic and resistance-type activities may confer a better effect on lipoprotein profile in healthy individuals than aerobic activities alone.

Perceived fatigue is comparable between different disease groups

Jones, D.E.J., Gray, J.C., Newton, J. — Wed, 19 Aug 2009 06:52:14 PDT

Background: Studies have established that levels of fatigue vary between different patient groups. It is less clear whether the nature, as opposed to severity of fatigue differs between groups.

Objective: To examine descriptions of fatigue by patients with a range of chronic diseases and determine the relationship between symptom domains.

Design: Retrospective review of Fatigue Impact Scale (FIS) data.

Setting: Fatigue Research Group.

Participants: Six hundred subjects in five chronic disease groups and one (n = 45) normal control group.

Main outcome measures: Statistical analysis was performed to assess the effect of increasing fatigue and the overlap of FIS domain scores between disease groups by calculation of geometric means as proportions summed to 1 in each FIS domains, whilst controlling for total score.

Results: Those with lower scores exhibit relatively higher physical scores than patients with higher total scores. In contrast, as total score increases, so does the proportion accounted for by the cognitive and psychosocial scores. This was not related to a threshold effect as the maximum total score of 40 in the physical domain was only achieved in three patients (<1%). Average domain proportions between patient groups did not vary to any degree among physical (0.30–0.39), cognitive (0.15–0.23) and psychosocial (0.42–0.47) domain proportions of the patient groups.

Conclusion: Perceived fatigue is similar between patient groups. Increasing scores were not related to simply reaching the maximum threshold in the physical domain. Studies have confirmed a positive-structured approach to symptom management in one fatigue-associated chronic disease, primary biliary cirrhosis, leads to significant improvements in quality of life. We suggest that, with a similar approach, the same might be true in other chronic diseases where moderate fatigue is a significant problem.

Statin therapy, muscle function and falls risk in community-dwelling older adults

Scott, D., Blizzard, L., Fell, J., Jones, G. — Wed, 19 Aug 2009 06:52:14 PDT

Background: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines.

Aim: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults.

Design: A prospective, population-based cohort study with a mean follow-up of 2.6 years.

Methods: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users.

Results: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI –0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (–5.02 kg, 95% CI –9.65 to –0.40) and LMQ (–0.30 kg/kg, 95% CI –0.59 to –0.01), and trended towards increased falls risk (0.13, 95% CI –0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (–16.17 kg, 95% CI –30.19 to –2.15) and LMQ (–1.13 kg/kg, 95% CI –2.02 to –0.24) compared to those who had ceased statin use at follow-up.

Conclusion: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.

The Association of Physicians of Great Britain and Ireland 2009

Wed, 19 Aug 2009 06:52:14 PDT

Incomplete Carney triad--a review of two cases

Sawhney, S.A., Chapman, A.D., Carney, J.A., Gomersall, L.N., Dempsey, O.J. — Wed, 19 Aug 2009 06:52:14 PDT

A curious association of three rare tumours was described by Carney in 1977. ‘Carney's triad’ characteristically includes multifocal pulmonary chondroma, gastric stromal sarcoma and extra-adrenal paraganglioma. Patients may exhibit complete or incomplete expression of the triad. Carney acknowledged that, of 79 patients, only 17 possessed all three tumours. We report here two patients with incomplete expression of Carney's triad.

Life-threatening scrotal pain

Sun, J.-T., Tsai, K.-C., Wu, C.-J., Lien, W.-C., Wang, H.-P. — Wed, 19 Aug 2009 06:52:14 PDT

Dyslipidemia and cardiovascular risk: the importance of early prevention

Miller, M. — Wed, 19 Aug 2009 06:52:14 PDT

Strategies aimed at primary prevention provide an outstanding opportunity for reducing the onset and burden of cardiovascular (CV) disease. Lipid abnormalities, including high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C), are associated with an increased risk of CV events, thereby serving as contributors to this process. By consensus, lowering LDL-C, generally with statin therapy, is the primary target of lipid-lowering therapy. However, statin therapy may be insufficient for patients with mixed dyslipidemia, especially those with insulin resistance syndromes. While the addition of niacin, fibrate or omega-3 fatty acids may be useful in this setting, outcomes data are lacking. Therefore, data from ongoing prospective studies will hopefully resolve this issue and facilitate identification of optimal strategies to augment CV risk reduction.

Red-green blindness

Seaton, A. — Wed, 19 Aug 2009 06:52:14 PDT