Prognostic significance of the neutrophil count in immunocompetent patients with bacteraemia

To examine the prevalence of neutropaenia in immunocompetent,bacteraemic patients, and whether it carries an independentrisk for mortality, we surveyed 2096 bacteraemic patients withoutmalignant diseases, and who were not receiving cytotoxic drugs.The granulocyte count on the day of the first positive bloodculture was < 1 x10⁹ cells/l in 33 patients (1.7%, group1); 1.0–4.0 x 10⁹ cells/l in 154 patients (7.9%, group2); 4.0–8.0 x 10⁹ cells/l in 564 patients (29%, group3); 8.0–;20.0x10⁹ cells/; in 1034 patients (53%, group4); and >20.0x10⁹ cells/l in 163 patients (8.4%, group 5).The mortality rates in the five groups were 39.4%, 18.8%, 18.1%,25.7% and 25.8%, respectively (p=0.0001). The main pathogensin group 1 were Staphylococcus aureus in 25% of patients andPseudomonas sp. in 23%. Mortality in group 1 patients was higherthan in the other patients (odds ratio 1.4, 95% Cl 1.1–1.9).Mortality was also significantly higher in group 2 patientswith high blood urea nitrogen. The percentage of neutropaenic,septic patients without known risk factors for neutropaeniais small, but their mortality is high. Overall mortality inpatients with relative neutropaenia (1.0–4.0x10⁹ cells/l)is low, but a subgroup of patients with high blood urea nitrogenis at considerable risk for a fatal outcome. High leucocytecounts are also a marker of increased risk for mortality, butthis association is not an independent prognostic factor.     

Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study

Following a femoral neck fracture and vertebral compressionfractures in two patients with severe haemophilia A, bone densityand turnover were measured in 19 males with severe haemophiliaA (all HIV negative, 18/19 hepatitis C antibody positive) andin 19 age/sex matched controls. Bone density at the lumbar spine(L2–4), measured by dual energy X-ray absorptiometry,was significantly lower in the haemophiliac patients (HPs) at(mean ± SEM) 1.109 ± 0.042 g/cm² vs. 1.234 ±0.027 in controls; p = 0.018. Femoral neck density was alsolower at 0.877 ± 0.034 g/cm² (HPs) vs. 1.067 ±0.032; p< 0.0005. No significant differences were evidentbetween the groups for serum calcium, parathyroid hormone, luteinizinghormone, follicle-stimulating hormone or 1,25 dihydroxyvitaminD3, nor for fasting urinary hydroxyproline, pyridinoline ordeoxy-pyridinoline excretion. Serum total alkaline phos-phatasewas elevated in HPs at 200 ±10 U/l vs. 158 ± 8;p = 0.004. Similarly, -glutamyl transferase was elevated at42 ±7 U/l (HPs) vs. 20 ±2; p = 0.007. Serum totaltestosterone and sex-hormone-binding globulin (SHBG) were higherin HPs at 26 ± 2.5 nmol/l vs. 17.4 ± 1.6 (p =0.009) and 56 ±6 nmol/l vs. 27 ± 3 (p = 0.0005),respectively. Free androgen index, however, was lower in HPsat 44 ± 5 vs 69 ± 7; p = 0.008. These resultssuggest significant osteopenia associated with haemophilia A.This may be partly due to liver dysfunction in HPs, but otherfactors, e.g. relative immobilization, may also be relevant.     

Brainstem perfusion is impaired in chronic fatigue syndrome

We looked for brain perfusion abnormalities in patients withmyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).An initial pilot study revealed widespread reduction of regionalbrain perfusion in 24 ME/CFS patients, compared with 24 normalvolunteers. Hypoperfusion ofthe brainstem (0.72±0.05vs. 0.80±0.04, p<0.0001) was marked and constant.We then tested whether perfusion to the brainstem in ME/CFSpatients differs from thatin normals, patients with major depression,and others with epilepsy. Data from a total of 146 subjectswere included in the present study: 40 normal volunteers, 67patients with ME/CFS(24 in the pilot study, 16 with no psychiatricdisorders, 13 with ME/CFS and depression, 14 with ME/CFS andother psychiatric disorders), 10 epileptics, 20 young depressedpatientsand 9 elderly depressed individuals. Brain perfusionratios were calculated using ⁹⁹Tc^m-hexamethylpropylene amineoxime (⁹⁹Tc^m- HMPAO) and single-photon emission tomography (SPET)with a dedicated three-detector gamma camera computer/system(GE Neurocam). Brainstem hypoperfusion was confirmed in allME/CFS patients. Furthermore, the 16 ME/CFS patients with nopsychiatric disorders and the initial 24 patients inthe pilotstudy showed significantly lower brainstem perfusion (0.71$0.03)than did depressed patients (0.77$0.03; ANOVA, p<0.0001).Patients with ME/CFS have a generalized reduction of brain perfusion,with a particular pattern of hypoperfusion of the brainstem.     

Prevalence of chronic kidney disease stages 3-5 among acute medical admissions: another opportunity for screening

Background: Early identification of chronic kidney disease (CKD)can help delay or prevent its progression, but the opportunitiesfor systematic screening of patients are not well defined. Aim: To define the prevalence of CKD Stages 3–5 and relatedanaemia among acute medical admissions. Design: Retrospective analysis. Methods: We studied all acute medical admissions to a majorLondon teaching hospital during one year. The lowest creatinine,highest haemoglobin (Hb) and average mean corpuscular volume(MCV) were determined for 3 months before and after admission.Patients were categorized as CKD Stages 3–5 if the highestestimated GFR (eGFR) was <60 ml/min/1.73 m². CKD-relatedanaemia was diagnosed if these patients had Hb <11 g/dl withnormal MCV. Results: A total of 6073 patients were studied: male 49.0%,age 65.4 ± 19.6 years (mean ± SD), creatinine82.7 ± 46.7 µmol/l, eGFR 89.1 ± 32.5 ml/min/1.73m², Hb 13.6 ± 1.73 g/dl, MCV 87.7 ± 7.2 fl. Therewas an inverse correlation between eGFR and age (r² = 0.5; P< 0.001). Males were younger than females (63.5 ±18.4 years vs. 67.3 ± 20.5) and had higher eGFR (93.6± 34.1 vs. 84.7 ± 30.2 ml/min/1.73 m²; P <0.001). A total of 743 patients (12.2%) had raised creatinine>110 µmol/l, however using eGFR <60 ml/min/1.73m², 1075 patients (17.7%) were identified. The patients werecategorized as follows: Stage 3: 950 (15.6%), Stage 4: 100 (1.7%),Stage 5: 25 (0.4%). Ninety-nine (9.2%) of the 1075 patientshad normocytic anaemia. Conclusions: We have found a high prevalence of CKD Stages 3–5(17.7%) among acute medical admissions, of whom 9.2% had a relatedanaemia. Our findings highlight an important opportunity (amongstthe 1.9 million acute medical admissions annually in England)for detecting patients with CKD.     

Patterns of Insulin Dependence in an African Diabetic Clinic

SUMMARY Analysis of the age of onset of diabetes amongst insulin-treatedpatients in a large African diabetic clinic revealed a bimodaltype of distribution, 23 per cent having an age of onset before30 years and 77 per cent with onset at 30 years of age. All66 of the young insulin-treated group (21.7±4.8 years(mean±1 SD)), and a random selection of 50 older insulin-treatedpatients (49.7±10 years), were studied. The older groupwere better controlled (HbA₁ 8.4±1.7 per cent vs. 10.8±2.6per cent, p<0.001), on lower doses of insulin (49±23vs. 71±23 u/day, p<0.001) and had higher body massindex (26.0±5.6 vs. 21.8±3.5, p<0.001). SerumC-peptide (0.24±0.15 vs. 0.07±0.10 nmol/l, p<0.0001),and C-peptide/glucose ratio (2.57±2.65 vs. 0.56+0.98nmol/mmolx 10², p<0.001) were very significantly higher inolder patients. Patients with later onset disease thus had betterpreservation of pancreatic function, higher body mass indexand better glycaemic control on lower doses of insulin. Thesefeatures suggest that older insulin-treated patients could infact be ‘Type 2’ or non-insulin dependent patients,and the condition may be controllable with diet and/or oralhypoglycaemic agents, at least in some.     

Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease

In a multi-centre retrospective study, we compared clinicaland laboratory data in 913 patients with cryoglobulinaemias,divided as: (i) essential cryoglobulinaemias; (ii) cryoglobulinaemiassecondary to connective tissue diseases (CTD), lymphoproliferativeor other haematological diseases (LPD), chronic liver diseases(CLD), and ‘other diseases’. Purpura was the commonestpresenting feature in all groups and was more common in essentialcryoglobulinaemias (p<0.0001). Meltzer's triad (purpura,arthralgia, weakness) was less frequent, but similarly distributed.Renal involvement was randomly distributed. Neurological impairmentwas less frequent in cryoglobulinaemias secondary to CLD (p<0.002).Raynaud's phenomenon, arthritis and sicca syndrome were morefrequent in cryoglobulinaemias secondary to CTD. Essential cryoglobulinaemiashad a significantly higher percentage of serum complement C4<8mg/dl (p<0.004), of detectable rheumatoid factor activity(p<0.0002), and of type II cryoglobulins (p<0.0001). Liverinvolvement was evident at presentation in 32.6% of essentialcryoglobulinaemias, 27.1% of cryoglobulinaemias secondary toLPD and 12.2% of cryoglobulinaemias secondary to CTD. Antibodiesto hepatitis B surface (HBsAg) and core (HBc) antigens weremore frequent in cryoglobulinaemias secondary to CLD; anti-HBsantibodies were randomly distributed. Antibodies to hepatitisC (HCV) were tested for in 224 patients, and prevalence washigh in all the groups, but lower in cryoglobulinaemias secondaryto CTD (p<0.0001). Type II and type III essential cryoglobulinaemiasdiffered significantly in renal involvement (p<0.0001), cryocrit< 3 % (p<0.0001), C4 <15 mg/dl (p<0.001), HBsAgprevalence (p<0.01) and purpura (p<0.05). Despite thehigh prevalence of HCV markers in all groups, the role of HCVin essential cryoglobulinaemia is not well defined; HBV seemsto play only a marginal role.     

Lipoprotein(a) as a determinant of the severity of angiographically defined carotid atherosclerosis

We measured fasting serum lipids, lipoproteins, apolipoproteinsand lipoprotein(a) [Lp(a)] in 49 Caucasian patients with transientischaemic attacks undergoing carotid angiography. The severityof extracranial cerebrovascular disease was assessed visuallyby a highly reproducible grading system that focused on theinternal carotid artery and carotid bifurcation. Compared witha healthy reference group, patients had significantly higherserum concentrations of: total cholesterol (mean ± SD),6.2 ± 1.6 vs. 5.6 + 1.0 mmol/l, p = 0.02; apolipoproteinB, 1.4 ±0.5 vs. 1.2±0.3g/l, p = 0.03; triglyceride[geometric mean(95% Cl)], 2.02(1.75–2.32) vs. 1.66(0.67–4.06)mmol/l, p = 0.03; and Lp(a), 0.33(0.26–0.42) vs. 0.17(0.40–0.76)g/l, p <0.001. Regression analysis showed that of the lipoprotein-relatedvariables, only Lp(a) was significantly related to the severityof carotid artery disease (p = 0.04) in the patients; this associationremained significant after adjusting for age, sex, blood pressure,and a history of stroke. Serum Lp(a) concentration was significantlyhigher in patients with carotid artery disease severity scoreabove the median value of the sample population compared withthose below the median: 0.45 vs. 0.24 g/l (95% Cl for difference0.35–0.88), p = 0.01. Elevated serum Lp(a) is a significantdeterminant of the extent of carotid atherosclerosis and maybe useful in identifying patients most at risk of stroke.     

Hypoglycemic episodes predict length of stay in patients with acute burns

Hypoglycemic episodes are associated with worse hospital outcomes. All adult patients admitted to our burn center from 2015 to 2019 were retrospectively reviewed. Patient demographics and burn characteristics were recorded. The primary outcome was mortality, and secondary outcomes were total length-of-stay and intensive care unit length-of-stay. All patients experiencing at least one hypoglycemic episode were compared to patients who did not experience hypoglycemia. There were 914 patients with acute burns admitted during the study period, 33 of which (4%) experienced hypoglycemic episodes. Of these, 17 patients (52%) experienced a single hypoglycemic episode, while the remainder experienced multiple hypoglycemic episodes. Patients with one or more hypoglycemic events were matched to non-hypoglycemic controls using propensity matching. Patients that experienced hypoglycemia had significantly less TBSA involvement (5% vs. 13%,median, p < 0.0002), higher prevalence of diabetes (48% vs. 18%, p < 0.0001), higher mortality (18% vs. 7%, p = 0.01), longer total length-of-stay (22 vs. 8 days, median, p < 0.0001), and longer ICU length-of-stay (12 vs. 0 days, median, p < 0.0001). A single hypoglycemic episode was associated with prolonged total (IRR = 1.91, p < 0.0001) and ICU length-of-stay (IRR = 3.86, p < 0.0001). Hypoglycemia was not associated with higher mortality in the survival analysis (p = 0.46).     

Base excess and lactate as prognostic indicators for patients admitted to intensive care

Objective: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. Design: Observational study. Setting: University teaching hospital general adult intensive care unit. Patients: 148 consecutive patients admitted to the intensive care unit. Interventions: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. Measurements and results: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than –4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5 %, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. Conclusions: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit. Received: 18 April 2000 Final revision received: 15 May 2000 Accepted: 15 May 2000     

The clinical course of patients with septic abortion admitted to an intensive care unit

Objective The purpose of this study was to describe the clinical course, complications, and outcome of patients with septic abortion admitted to the intensive care unit (ICU).Design, setting, and patients In this retrospective study, the records of 63 patients with septic abortion admitted to the ICU of a university hospital in Argentina between 1985 and 1995 were reviewed.Results The mean age of the patients was 28.5 years, and 33% had had previous abortions. The mean gestational age was 10.5 weeks. The first ICU day Acute Physiology and Chronic Health Evaluation (APACHE) II mean score was 13.9. Acute renal failure developed in 73% (46 of 63) of the patients, disseminated intravascular coagulation (DIC) in 31% (15 of 49), and septic shock in 32% (20 of 63). Blood cultures were positive in 24% (15 of 62). Twelve patients died (19%). Eight of the deaths occurred during the first 48 h of the ICU admission. Compared with survivors, non-survivors had higher median number of organ failures (1.0 vs 4.0, p<0.0001), mean first ICU day SOFA scores (6.6 vs 10.0, p=0.0059), and mean APACHE II scores (12.7 vs 20.2, p=0.0003), and were more likely to have septic shock (18 vs 92%, p<0.0001), and receive dopamine (37 vs 83%, p=0.0040), mechanical ventilation (8 vs 83%, p<0.0001), and pulmonary artery catheter (8 vs 41%, p=0.0026).Conclusions Although it is an avoidable complication, septic abortion requiring admission to the ICU is associated with high morbidity and mortality.     

Asymptomatic Thrombocytopenia Developing During Pregnancy (Gestational Thrombocytopenia) - A Clinical Study

During pregnancy some women develop unexplained thrombocytopenia(gestational thrombocytopenia). Previous studies have detectedabnormal platelet antibodies, suggesting an autoimmune aetiology.To determine whether gestational thrombocytopenia is associatedwith increased maternal bleeding or adversely addressed affectsthe fetus, 31 pregnant women with asymptomatic thrombocytopeniawere compared with 12 women with thrombocytopenia associatedwith pre-eclampsia and 34 normal pregnant controls. There wasno increase in maternal bleeding in those with asymptomaticthrombocytopenia compared with the normal controls, but pre-eclampticwomen experienced more bleeding (mean difference 181 ml, 95per cent confidence limits 50-312 ml, p < 0.01). There wasno difference in the mean weights of the babies or placenta,nor in the APGAR scores between infants born to controls andthose with asymptomatic thrombocytopenia. Cord blood plateletlevels were measured in 26 women with asymptomatic thrombocytopeniaand were normal in 25 and mildly reduced in one. Thus measuresused for the treatment and delivery of pregnancies complicatedby autoimmune thrombocytopenia are not indicated in gestationalthrombocytopenia. Pregnant women should not be considered thrombocytopeniaunless the platelet count has fallen below 120 x 10⁹/l.     

Malaria prophylaxis: identifying risk groups for non-compliance

To investigate behaviour in the use of drug prophylaxis againstmalaria and the risk factors for noncompliance, 507 Europeanor North American travellers returning from endemic areas werestudied retrospectively at Berlin in a 11-year periad from 1980to 1990. Compliance was significantly correlated with shortertravel duration: the group with good compliance stayed 37.2±38.5days (mean±SD) in contrast to 69.8±93.5 days inthe group of patients with no compliance (p = 0.00001). Olderpatients were significantly more compliant than patients aged<55 years (20/27 compliant at >54 years vs. 175/476 at< 55 years; p = 0.0001 ). Compliance was significantly affectedby travel destination (Southern and East African regions; p= 0.0054), age (< 15 and < 55 years, respectively; p =0.0001), and reason of travel (package tours; p = 0.0001). CARTanalysis confirmed logistic regression analysis with respectto age and travel type, and revealed that patients using onlyone information source were significantly more compliant thanthose using two or more information sources. Travel agencieswere nearly as well informed as Institutes of Tropical Medicine,but family doctors had a significant incidence of giving wrongadvice. This study should enable medical personnel dealing withprophylactic advice against malaria to identify patients athigh risk for noncompliance, and to educate them more carefullythan other travellers regarding antimalarial drug prophylaxis.     

Biological Activity of Autoantibodies From Patients With Thyroid-associated Ophthalmopathy: In Vitro Effects on Porcine Extraocular Myoblasts

To determine whether antibodies to orbital tissue have a pathogenicrole in thyroid-associated ophthalmopathy, the in vitroeffectsof IgG from patients with thyroid-associated ophthalmopathyon porcine extraocular myoblast growth were studied. Growthof primary extraocular myoblast cultures and extraocular myoblastclones was stimulated by patients' IgG, as measured by [³H]thymidineuptake and bromodeoxyuridine incorporation. Myoblasts respondedin a dose-related fashion to increasing concentrations of patients'IgG, and the response was reversed by anti-human IgG. The growthstimulating effect of patients' IgG was relatively specificto extraocular myoblasts, compared to skeletal myoblasts. IndividualIgG samples from 36 patients with ophthalmopathy gave rise tohigher growth responses of cloned extraocular myoblasts, thaneither 31 normal controls (p<0.005), or IgG from 10 patientswith Graves' disease without evidence of ophthalmopathy (p<0.001).Myoblast growth-stimulating antibody did not correlate withthyroid autoantibody levels (thyrotrophin receptor antibodyor thyroid microsomal antibody levels), but correlated significantlywith binding to extraocular muscle membranes (r=0.524, p<0.001).Eye-muscle stimulating antibodies were demonstrable in seraof patients with thyroid-associated ophthalmopathy, and maybe responsible for the enlargement of eye muscle in this disease.     

Plasmodium falciparum Hyperparasitaemia: use of Exchange Transfusion in Seven Patients and a Review of the Literature

During the last 15 years, at least 35 patients with severe falciparummalaria or babesiosis have recovered following treatment byexchange of up to 10 1 of blood. In a patient treated in Manchester,a parasitaemia of 2.10 x 10⁶ µl (42 per cent) was virtuallyeliminated over eight hours by a 3.5 litre exchange blood transfusion.However, the equipment and amounts of compatible blood requiredfor total exchange are rarely available in areas endemic formalaria and the risks of the procedure, including transfusion-relatedinfections, are high. Partial exchange transfusion with oneto two litres of blood carried out over two to seven hours,reduced Plasmodium falciparum parasitaemias of 0.33–1.48x 10⁶/µl (13–38 per cent) to 0.11–0.81 x 10⁶(4–17 per cent) in six Thai patients who were receivingintravenous quinine. The reduction in parasitaemia ranged from0.13–0.67 x 10⁶ µl (9–12 per cent) withinsix hours. During the same period, parasitaemia in 13 patientswith cerebral malaria treated with chemotherapy alone showedlittle reduction from initial levels of 0.20–1.74 x 10⁶/µl(11–42 per cent). One of the patients who were treatedwith exchange transfusion died with intractable hypotensionbefore the procedure could be completed and two others developedoliguric renal failure which was controlled by peritoneal dialysis.Partial exchange transfusion is a promising and practical alternativeto total exchange where facilities are limited. It deservesfurther assessment in the rural tropics.     

Combined bezafibrate and simvastatin treatment for mixed hyperlipidaemia

The safety and efficacy of combined bezafibratesimvastatin therapywas evaluated in 49 patients with diet-resistant mixed hyperlipidaemia(type Mb). After a two-month placebo phase, patients were randomizedto receive either Bezafibrate Slow Release (SR) 400 mg maneor simvastatin 20 mg nocte followed by three months combinationtherapy. Total cholesterol, triglycerides and high-density lipoprotein(HDL) cholesterol were measured at monthly intervals. Apolipoproteins(apo) A1 and B, lipoprotein (a) [Lp(a)] and fibrinogen weremeasured before and after each treatment. Simvastatin was moreeffective than Bezafibrate SR in reducing total cholesterol(2.0 vs. 1.1 mmol/l, p=0.003) and lowering LDL cholesterol (1.7vs. 0.4 mmol/l, p= 0.0001) whereas Bezafibrate SR was more effectivein reducing triglycerides (by 41% vs. 17%, p= 0.001) and fibrinogen(by 23% vs. 3%, p= 0.004). Compared with simvastatin monotherapy,combined drug therapy induced further reductions in triglycerides(by 26%, p= 0.0003) and apoB (by 11 mg/dl, p=0.03) and an increasein apoA1 (by 21 mg/dl, p= 0.0008). Symptomatic and biochemicaladverse events did not occur more frequently on combined drugtherapy than on monotherapy. The combination of bezafibrateand simvastatin was more effective in controlling mixed hyperlipidaemiathan either drug alone and did not provoke more adverse events.     

Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion capacity

The mixed expired nitric oxide (NO) production of the lungsof patients with primary pulmonary hypertension (PPH) and normalsubjects was measured to determine the relationship betweenNO production and the diffusion capacity of the lung (KCO).Expired air was collected from eight patients with PPH and 20healthy volunteers for analysis by a chemluminescent analyser.Mean pulmonary artery pressure in the PPH patients was 59.5± 6.45 mmHg and their mean cardiac output was 2.95 ±0.35 l/min. All patients and subjects underwent measurementsof FEV1, VC and KCO. The rate of production of NO in mixed exhaledair was lower in the PPH group compared to the controls (2.85± 0.7 vs. 4.69 ± 0.35 nM/min; p<0.05). Therewas a good correlation of expired NO with the KCO (r=0.7; n=30;p<0.001). When corrected, KCO differences in exhaled NO werenot significant (p=0.09). We conclude that the low exhaled NOobserved in PPH patients is a reflection of the reduced bloodcapillary volume in these patients rather than a decreased basalproduction of NO.     

A Comparative Study of the Relative Effects of Anticonvulsant Drugs and Dietary Folate on the Red Cell Folate Status of Patients with Epilepsy

In a survey of the red cell folate status of 200 patients withepilepsy, compared to 72 controls, we found that median redcell folate levels were reduced significantly in patients treatedwith phenytoin (p<0.01) or carbamazepine (p<0.001) alone.Patients taking more than one drug had reduced levels also (p<0.001),but in patients treated with sodium valproate alone there wasno significant decrease in red cell folate levels compared tocontrols. Twenty-two per cent of patients in the group takingmore than one drug had reduced levels of red cell folate comparedwith 17 per cent of those taking carbamazepine alone, 13 percent of those taking phenytoin only, and 9 per cent of thosetaking sodium valproate only. Dietary folate intake was significantlyreduced in all the patient groups compared with controls (p<0.001for the carbamazepine and phenytoin groups, p<0.01 for thepolypharmacy and sodium valproate groups); a significant correlation,between red cell folate levels and dietary folate was not established. Significant negative relationships were established betweencarbamazepine dose (r=0.35, p<0.01) or serum level (r=-0.27,p<0.05) and red cell folate level in patients on one drugonly. The correlation between dose or serum level-of phenytoinand red cell folate level was also negative but did not reachsignificance. Our findings show that all anticonvulsant drugs interfere withfolate metabolism. While the effect is greatest with drugs whichinduce microsomal liver enzymes, low levels of folate also occurredin patients taking the non-enzyme inducer sodium valproate.Although a significant relationship between diet and red cellfolate was not established, dietary folate could be a furthercontributory factor.     

Fever as the presenting complaint of travellers returning from the tropics

We investigated prospectively the cause of fever in patientsrequiring hospitalization after returning from the tropics.All consecutive admissions (n=195) with oral temperature >37.0°Cat the time of admission were enrolled. Final diagnosis as recordedon the discharge summary by the attending physician and resultsof any relevant laboratory or radiological investigations wererecorded on standard proforma. Malaria accounted for 42% ofadmissions; two patients had returned to Britain more than 6months before presentation. The second largest group was assumedto have a non-specific viral infection (25%). Cosmopolitan infections(urinary tract infection, community-acquired pneumonia, streptococcalsore throat, etc.) accounted for 9%. Coincidental infections(schistosomiasis, filariasis, intestinal helminths) were foundin 16%. Serology was positive for HIV infection in 3%. The mostuseful investigation was a malaria film, which was positivein 45% of cases in which it was performed. The combination ofthrombocytopaenia (platelet count <100 x 10⁹) and hyperbilirubinaemia(bilirubin > 18 IU/ml) were useful predictive markers ofmalaria: all 23 patients with both abnormalities had positivemalaria films. Malaria must be excluded in any febrile patientreturning from the tropics. In the absence of a positive malariafilm, the combination of a low platelet count and raised bilirubinmay suggest the need for an empirical course of therapy.     

Hyperparathyroidism, glucose tolerance and platelet intracellular free calcium in chronic renal failure

Disturbance in the vitamin D/parathyroid hormone (PTH) axismay be important in the pathogenesis of glucose intoleranceand insulin resistance in uraemia. To investigate possible relationshipsbetween hyperparathyroidism, intracellular free calcium ([Ca²⁺]₁),and glucose tolerance in chronic renal failure, we measuredserum intact PTH (l-PTH) by two-site immunometric assay, platelet[Ca²⁺]₁ using the fluorescent indicator fura-2, and plasma glucoseand insulin after 14 h overnight fast and at 30, 60 and 120min following a 75 g oral glucose load, in 18 chronic haemodialysispatients with elevated serum l-PTH. Calcitriol (1 µg)was administered parenterally at the end of each dialysis sessionfor four weeks. This significantly decreased serum l-PTH (p<0.001)and platelet [Ca²⁺], (p<0.01). Uraemic patients initiallyshowed marked glucose intolerance, with increased area belowthe glucose curve compared to healthy controls, but after 4weeks of calcitriol treatment, this effect was significantlydecreased, and there was a significant rise in the area underthe insulin curve after glucose load. The insulinogenic indexalso increased significantly after calcitriol treatment. These data suggest that calcitriol treatment of haemodialysispatient with secondary hyperparathyroidism is associated withincreased insulin secretion in response to glucose challenge,and that this change is linked to the decrease in intracellularfree calcium.     

Dobutamine-induced increase of right ventricular contractility without increased stroke volume in adolescent patients with transposition of the great arteries: Evaluation with magnetic resonance imaging

Objective: Prognosis in patients with surgically corrected (Senning or Mustard) transposition of the great arteries (TGA) depends mainly on right ventricular (RV) function and RV functional reserve. We examined the role of dobutamine stress in the early detection of RV dysfunction in asymptomatic or slightly symptomatic patients with TGA using magnetic resonance imaging (MRI). Design and patients: Twelve asymptomatic or slightly symptomatic patients with chronic RV pressure overload, surgically corrected (Mustard or Senning) TGA (age 22.8 (±3.4) years; New York Heart Association (NYHA) class I/II) and nine age matched healthy volunteers (age 27.3 (±4.4) years) were included. MRI was applied both at baseline and during dobutamine stress (start dose 5 μg/kg/min to maximum dose 15 μg/kg/min) to determine RV and left ventricular (LV) stroke volumes (SV) and ejection fraction (EF). Results: At baseline only RVEF was significantly higher in controls than in patients (71 (±9) vs. 57 (±10)%, p < 0.001), other RV parameters were not significantly different between the two examined groups: RVSV (86 (±21) vs. 72 (±27) ml, p = ns), RV end-diastolic volume (EDV) (123 (±37) vs. 123 (±33) ml, p = ns), and heart rate (61 (±10) vs. 69 (±14) bpm, p = ns), respectively. During dobutamine stress RVEF increased significantly both in controls and patients (20 (±16) vs. 17 (±18)%, p < 0.01 and p < 0.02 vs. rest, respectively), but stress RVEF was significantly higher in controls than in patients (85 (±3) vs. 66 (±7)%, p < 0.0001). RVSV increased significantly in controls (22 (±19)%, p < 0.02), and there was no significant increase in RVSV in patients (?10 (±28)%, p = ns). The controls showed no change in RVEDV (2 (±17)%, p = ns), but in patients a significant decrease in RVEDV (?24 (±15)%, p < 0.001) was observed. Maximal heart rate was significantly higher in patients than in controls (122 (±20) vs. 101 (±14) bpm, p < 0.02). Conclusion: In asymptomatic or slightly symptomatic patients with surgically corrected TGA dobutamine had a positive inotropic effect on RV, but the increased contractility was not accompanied by an appropriate increase in SV. Our data suggest inadequate RV filling in this category of patients, possibly due to rigid atrial baffles and compromised atrial function or decreased compliance due to RV hypertrophy.