Juice powder concentrate and systemic blood pressure, progression of coronary artery calcium and antioxidant status in hypertensive subjects: a pilot study

Because micronutrients from plants may have beneficial cardiovasculareffects, the hypothesis that an encapsulated juice powder concentratemight affect several measures of vascular health was testedin free living adults at low cardiovascular risk. Blood pressure,vascular compliance, lipid and antioxidant markers, and serialelectron beam tomography (to calculate a coronary artery calciumscore as a measure of atherosclerosis burden), were monitoredin 51 pre-hypertensive and hypertensive subjects over 2 years.By the end of follow-up, systolic and diastolic blood pressuredecreased significantly (–2.4 ± 1.0 mmHg, P <0.05 and –2.2 ± 0.6 mmHg, P < 0.001), and largeartery compliance improved significantly (1.9 ± 0.6 mlmmHg^–1 x 100, P < 0.01). The progression of coronaryartery calcium score was smaller than expected compared witha historical database (P < 0.001). Laboratory testing showeda significant decrease in homocysteine (P = 0.05), HDL cholesterol(P = 0.025) and Apo A (P = 0.004), as well as a significantincrease in β-carotene, folate, Co-Q10 and -tocopherol(all P < 0.001). The phytonutrient concentrate we utilizedinduced several favorable modifications of markers of vascularhealth in the subjects. This study supports the notion thatplant nutrients are important components of a heart healthydiet.     

The Relationship Between Long-term Glycaemic Control and Diabetic Nephropathy

Urine albumin excretion was studied by two widely accepted methodsin 210 patients with insulin-dependent diabetes mellitus andrelated to the mean of serial glycosylated haemoglobin (HbA₁)measurements made every 3 months during the previous 6 years.Microalbuminuria (albumin excretion rate > 20 µg/min)was present in 9.5 per cent of patients when defined by a 24-hourcollection and 8.1 per cent of patients when defined by a timedovernight urine sample. Those with microalbuminuria, as estimatedfrom a timed overnight urine sample, had a longer duration ofdiabetes but otherwise did not differ in age, duration of diabetesor arterial blood pressure from patients whose albumin excretionrate was 20 µg/min or less irrespective of the methodof urine collection. The mean and the most recent HbA₁ levelsdiffered significantly between the normal and the microalbuminuriagroups when defined by the 24-hour albumin excretion rate (p<0.001,p<0.01), but no significant difference between these groupswas found when albumin excretion rates were calculated fromthe timed overnight urine sample. Albumin excretion rate, examinedin relation to mean HbA₁, increased significantly with worseningglycaemic control whether measured over 24 hours or overnight(p<0.05, p< 0.01). These findings support an associationbetween glycaemic control and microalbuminuria, but the correlationis weak, dependent on the method of urine collection and isjust as good for a relatively short-term as for a long-termmeasure of average blood glucose.     

Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant Analogues of Mussel Defensin

We previously reported the crucial role displayed by loop 3of defensin isolated from the Mediterranean mussel, Mytilusgalloprovincialis, in antibacterial and antifungal activities.We now investigated antiprotozoan and antiviral activities ofsome previously reported fragments B, D, E, P and Q. Two fragments(D and P) efficiently killed Trypanosoma brucei (ID₅₀ 4–12µM) and Leishmania major (ID₅₀ 12–45 µM) ina time/dose-dependent manner. Killing of T. brucei started asearly as 1 h after initiation of contact with fragment D andreached 55% mortality after 6 h. Killing was temperature dependentand a temperature of 4°C efficiently impaired the abilityto kill T. brucei. Fragments bound to the entire external epitheliumof T. brucei. Prevention of HIV-1 infestation was obtained onlywith fragments P and Q at 20 µM. Even if fragment P wasactive on both targets, the specificity of fragments D and Qsuggest that antiprotozoan and antiviral activities are mediatedby different mechanisms. Truncated sequences of mussel defensin,including amino acid replacement to maintain 3D structure andincreased positive net charge, also possess antiprotozoan andantiviral capabilities. New alternative and/or complementaryantibiotics can be derived from the vast reservoir of naturalantimicrobial peptides (AMPs) contained in marine invertebrates.     

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.     

Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3'-digallate (TF3)

SARS-CoV is the causative agent of severe acute respiratorysyndrome (SARS). The virally encoded 3C-like protease (3CL^Pro)has been presumed critical for the viral replication of SARS-CoVin infected host cells. In this study, we screened a naturalproduct library consisting of 720 compounds for inhibitory activityagainst 3CL^Pro. Two compounds in the library were found to beinhibitive: tannic acid (IC₅₀ = 3 µM) and 3-isotheaflavin-3-gallate(TF2B) (IC₅₀ = 7 µM). These two compounds belong to agroup of natural polyphenols found in tea. We further investigatedthe 3CL^Pro-inhibitory activity of extracts from several differenttypes of teas, including green tea, oolong tea, Puer tea andblack tea. Our results indicated that extracts from Puer andblack tea were more potent than that from green or oolong teasin their inhibitory activities against 3CL^Pro. Several otherknown compositions in teas were also evaluated for their activitiesin inhibiting 3CL^Pro. We found that caffeine, (—)-epigallocatechingallte (EGCg), epicatechin (EC), theophylline (TP), catechin(C), epicatechin gallate (ECg) and epigallocatechin (EGC) didnot inhibit 3CL^Pro activity. Only theaflavin-3,3'-digallate(TF3) was found to be a 3CL^Pro inhibitor. This study has resultedin the identification of new compounds that are effective 3CL^Proinhibitors.     

Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles

Ginkgo biloba extract (GBE) is composed mostly of two constituents: One is terpenoids (such as bilobalide, ginkgolides A, B and C), and the other is flavonoids (such as quercetin and rutin). After oral administration of GBE (160 mg) to healthy volunteers, the plasma concentrations of ginkgolides A and B and bilobalide are 41.8, 5.6 and 37.6 ng/ml, respectively. GBE and bilobalide cause a potent concentration-dependent relaxation. NG-Monomethyl-l-arginine acetate (l-NMMA), an NO synthesis inhibitor, reduces the vasodilation induced by GBE. Furthermore, the vasorelaxation of GBE is attenuated in Ca2+-free medium. Bilobalide possesses similar mechanisms. The other constituents also produce vasorelaxation. On the other hand, all the compounds markedly modify the action potential configuration in guinea pig ventricular cardiomyocytes. GBE prolongs the action potential duration (APD), whereas bilobalide shortens the APD. In patch-clamp experiments, GBE markedly inhibits the Ca2+ current (ICa), the delayed rectifier K+ current (IK) and the inwardly rectifying K+ current (IK1). On the contrary bilobalide enhances the ICa and IK currents concentration-dependently. The other constituents do not cause their actions in a uniform direction. In the rat sino-atrial (SA) node, GBE causes a negative chronotropic effect. These results indicate that GBE and the constituents produce effective electropharmacological actions in the cardiomyocytes and cause vasodilation, mainly due to the inhibitions of Ca2+ influx through the Ca2+ channel and the activation of NO release in the endothelium and aortic vascular muscles.     

Anti-stress and Adaptogenic Activity of l-Arginine Supplementation

In the present study, oral supplementation of L-arginine inrats was evaluated for its anti-stress and adaptogenic activityusing the cold (5°C)–hypoxia (428 mmHg)–restraint(C-H-R) animal model. A dose-dependent study of L-arginine wascarried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0mg/kg body weight, administered orally 30 min prior to C-H-Rexposure. The time taken by the rat to attain a rectal temperatureof 23°C (T_rec 23°C) during C-H-R exposure and its recoveryto T_rec 37°C at normal atmospheric pressure and 32 ±1°C were used as biomarkers of anti-stress and adaptogenicactivity. Biochemical parameters related to lipid peroxidation,anti-oxidants, cell membrane permeability, nitric oxide andstress, with and without administration of the least effectiveL-arginine dose, were measured in rats on attaining T_rec 23°Cand T_rec 37°C. The least effective adaptogenic dose of L-argininewas 100.0 mg/kg body weight. The C-H-R exposure of control rats,on attaining T_rec 23°C, resulted in a significant increasein plasma malondialdehyde (MDA), blood lactate dehydrogenase(LDH) and a decrease in blood catalase (CAT) and plasma testosteronelevels. On recovery (T_rec 37°C) of control rats, there wasa further decrease in CAT and plasma testosterone, and an increasein LDH. L-Arginine supplementation resulted in a significantdecrease in plasma MDA, an increase in blood superoxide dismutase(SOD), CAT levels maintained at control values and a lower increasein LDH compared with controls (45.3 versus 58.5% and 21.5 versus105.2%) on attaining T_rec 23°C during C-H-R exposure andon recovery to T_rec 37°C. The results suggested that L-argininepossesses potent anti-stress activity during C-H-R exposureand recovery from C-H-R-induced hypothermia.     

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.     

Safety and efficacy of increasing wintertime vitamin D and calcium intake by milk fortification

We studied the safety and efficacy of milk fortified with vitaminD₃ and calcium. Over the winter, we conducted a double-blind,placebo-controlled trial of fortified milk (12µg vitaminD₃ and 1525 mg calcium per litre) compared to unfortified milk(0.3µg vitamin D₃ and 1270 mg calcium per litre) in 102adults (aged 17–54 years). Serum 25-hydroxyvitamin D [25(OH)D],ionized calcium, and creatinine were measured at baseline andafter intervention. Fortification reduced the seasonal declinein serum 25(OH)D concentrations by >50%. In the fortifiedgroup, serum 25(OH)D decreased by 15nmol/l from 77±35nmol/l to 62±26 nmol/l (p<0.001). In the control group,serum 25(OH)D fell by 31 nmol/l from 85±39 nmol/l to54±25 nmol/l (p<0.001). We suggest that milk enrichedwith vitamin D be provided in high-latitude European countriesto diminish the wintertime fall in serum 25(OH)D.     

Immunological and Psychological Benefits of Aromatherapy Massage

This preliminary investigation compares peripheral blood cellcounts including red blood cells (RBCs), white blood cells (WBCs),neutrophils, peripheral blood lymphocytes (PBLs), CD4⁺, CD8⁺and CD16⁺ lymphocytes, CD4⁺/CD8⁺ ratio, hematocrit, humoralparameters including serum interferon- and interleukin-6, salivarysecretory immunoglobulin A (IgA). Psychological measures includingthe State–Trait Anxiety Inventory (STAI) questionnaireand the Self-rating Depression Scale (SDS) between recipients(n = 11) of carrier oil massage and aromatherapy massage, whichincludes sweet almond oil, lavender oil, cypress oil and sweetmarjoram oil. Though both STAI and SDS showed a significantreduction (P < 0.01) after treatment with aromatherapy andcarrier massage, no difference between the aromatherapy andcontrol massage was observed for STAI and SDS. Aromatherapy,in contrast to control massage, did not significantly reduceRBC count or hematocrit. However, aromatherapy massage showeda significant (P > 0.05) increase in PBLs, possibly due toan increase in CD8⁺ and CD16⁺ lymphocytes, which had significantlyincreased post-treatment (P < 0.01). Consequently, the CD4⁺/CD8⁺ratio decreased significantly (P < 0.01). The paucity ofsuch differences after carrier oil massage suggests that aromatherapymassage could be beneficial in disease states that require augmentationof CD8⁺ lymphocytes. While this study identifies the immunologicalbenefits of aromatherapy massage, there is a need to validatethe findings prospectively in a larger cohort of patients.     

Studies on Intestinal Calcium Absorption in Patients with Idiopathic Hypercalciuria

Using an in vitro method, the uptake of radio-labelled Ca²⁺by jejunal biopsy specimens from control subjects, patientswith idiopathic hypercalciuria and patients with renal stoneswithout hypercalciuria, were compared. Radio-labelled Ca²⁺ uptakewas investigated over the concentration range 0.1–5.0mmol/1. For all subjects there was a linear relationship betweenCa²⁺ uptake and medium concentration suggesting that Ca²⁺ uptakewas a passive process. There was no significant difference inCa²⁺ uptake between control subjects and patients with renalstones without hypercalciuria. Patients with idiopathic hypercalciuria,both absorptive and renal subtypes, showed increased Ca²⁺ uptakeat all incubation medium concentrations. Assays of various biochemicalparameters including alkaline phosphatase, Ca²⁺-activated ATPase,cyclic AMP and Ca²⁺-binding protein, in jejunal biopsy specimensshowed no significant differences between control subjects andpatients with idiopathic hypercalciuria. The results suggestthat the intestinal abnormality inidiopathic hypercalciuriais due to enhanced permeability of the brush border membraneto Ca²⁺, possibly mediated by alterations in membrane lipids.     

In vitro anti-Candida Activity of Zataria multiflora Boiss

Zataria multiflora Boiss known as Avishan Shirazi (in Iran)is one of the valuable Iranian medicinal plants. The aim ofstudy was to evaluate anti-Candida activity of Z. multifloraagainst different species of Candida in vitro. Anti-Candidaactivity of the aqueous, ethanolic and methanolic macerationextract of the aerial parts of Z. multiflora Boiss was studiedin vitro. Anti-Candida activity against Candida species wasdone using serial dilutions of extracts in Sabouraud's dextroseagar. Minimal inhibitory concentration (MIC) of the methanolicand ethanolic extracts was 70.7 and 127 mg l^–1, respectively.Aqueous extract showed no remarkable activity against Candidaspecies. We conclude that methanolic extract of the aerial partsof Z. multiflora Boiss has more anti-Candida effect at 70.7mg l^–1 compared to ethanolic extract 127 mg l^–1.In addition, the isolates of Candida parapsilosis were moresusceptible to methanolic extract than other tested species.     

Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects

Blood was taken at the first antenatal clinic from 56049 pregnantwomen. Neural tube defect (NTD) pregnancies (81) were comparedto controls (247) for plasma vitamin B₁₂ (B₁₂) (ng/l), plasmafolate (µg/1), and red cell folate (RCF) (µg/l).Median values were significantly different and were, respectively,243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269and 338 (p < 0.001). There was a significant correlationbetween plasma B₁₂ and RCF in cases (r = 0.31, p = 0.004) butnot in controls (r = 0.02, p = 0.725). In cases only, multipleregression showed that both plasma B₁₂ and plasma folate influencedthe maternal RCF (multiple r = 0.68, p < 0.001). Plasma folateand plasma B₁₂ were independent risk factors for NTDs, suggestingthat the enzyme methionine synthase is involved directly orindirectly in the aetiology. The levels of folate and B₁₂ whereincreased risk occurred were not those usually associated withdeficiency, calling for a re-evaluation of their recommendeddaily allowances. Whether the aetiology is purely nutritionalor a metabolic defect, this study suggests that considerationshould be given to including B₁₂ as well as folic acid in anyprogramme of supplementation or food fortification to preventNTDs.     

Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects

Blood was taken at the first antenatal clinic from 56049 pregnantwomen. Neural tube defect (NTD) pregnancies (81) were comparedto controls (247) for plasma vitamin B₁₂ (B₁₂) (ng/l), plasmafolate (µg/1), and red cell folate (RCF) (µg/l).Median values were significantly different and were, respectively,243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269and 338 (p < 0.001). There was a significant correlationbetween plasma B₁₂ and RCF in cases (r = 0.31, p = 0.004) butnot in controls (r = 0.02, p = 0.725). In cases only, multipleregression showed that both plasma B₁₂ and plasma folate influencedthe maternal RCF (multiple r = 0.68, p < 0.001). Plasma folateand plasma B₁₂ were independent risk factors for NTDs, suggestingthat the enzyme methionine synthase is involved directly orindirectly in the aetiology. The levels of folate and B₁₂ whereincreased risk occurred were not those usually associated withdeficiency, calling for a re-evaluation of their recommendeddaily allowances. Whether the aetiology is purely nutritionalor a metabolic defect, this study suggests that considerationshould be given to including B₁₂ as well as folic acid in anyprogramme of supplementation or food fortification to preventNTDs.     

Intravenous Glucose Tolerance and Mortality in Non-insulin-dependent Diabetes Mellitus

Two hundred and forty-nine patients with non-insulin-dependentdiabetes were entered into a prospective study at diagnosisand examined at presentation and one, three, and five yearslater. Ten years after diagnosis, 34 patients were known tobe dead and 214 alive. A number of factors were significantlyassociated with survival on univariate analysis and appearedto form two independent intra-related groups: a ‘metabolic’group and a ‘degenerative condition’ group. Multivariateanalysis of these two groups showed that glucose tolerance (therate constant K_G for decrease in plasma glucose concentrationafter its intravenous injection) was significantly related tosurvival in the ‘metabolic’ group, and age, bloodpressure and anti-hypertensive therapy were significant in the‘degenerative’ group of factors. A low K_G valuewas more strongly associated with prognosis than any other factor.Values from the one year review were prognostically more usefulthan initial or later values. Indices of insulin secretion weresimilar irrespective of whether patients survived or died, andso we believe the lower K_G values of dead patients were dueto impaired insulin sensitivity. A regression, equation usingthe above factors correctly allocated survival outcome in 81%of subjects.     

Ozone Therapy for Tumor Oxygenation: a Pilot Study

Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy.Ozone therapy is a non-conventional form of medicine that hasbeen used successfully in the treatment of ischemic disorders.This prospective study was designed to assess the effect ofozone therapy on tumor oxygenation. Eighteen subjects were recruitedfor the study. Systemic ozone therapy was administered by autohemotransfusionon three alternate days over one week. Tumor oxygenation levelswere measured using polarographic needle probes before and afterthe first and the third ozone therapy session. Overall, no statisticallysignificant change was observed in the tumor oxygenation inthe 18 patients. However, a significant decrease was observedin hypoxic values 10 and 5 mmHg of pO₂. When individually assessed,a significant and inverse non-linear correlation was observedbetween increase in oxygenation and the initial tumor pO₂ valuesat each measuring time-point, thus indicating that the morepoorly-oxygenated tumors benefited most (rho = –0.725;P = 0.001). Additionally, the effect of ozone therapy was foundto be lower in patients with higher hemoglobin concentrations(rho = –0.531; P < 0.034). Despite being administeredover a very short period, ozone therapy improved oxygenationin the most hypoxic tumors. Ozone therapy as adjuvant in chemo-radiotherapywarrants further research.     

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.     

Abnormal Platelet Function and Ultrastructure in Fulminant Hepatic Failure

Evidence in favour of an acquired platelet defect in fulminanthepatic failure has been provided by studies of in vitro plateletaggregation with adenosine diphosphate (ADP). Platelets fromsix patients required a higher concentration (threshold concentration)of ADP to reach second phase aggregation than those from controls(12·3 compared with 2·2x10^–6 M). Plateletsfrom another six patients failed to show second phase aggregationat the highest concentration of ADP used (3·2x10^–6M). The degree of aggregation at a fixed concentration (3·2x^–6M) was significantly less than in controls (34·2 percent compared with 57·5 per cent). Capillary bleedingtimes correlated positively with the abnormalities of plateletaggregation. In crossover studies, platelet poor plasma fromthese patients did not inhibit platelet aggregation in controls,nor did platelet poor plasma from controls enable patients'platelets to reach second phase aggregation suggesting thatfactors other than the plasma were responsible for this abnormalplatelet function. Some relationship between the severity of hepatic necrosis andplatelet dysfunction can be deduced as platelet function wasnormal in 16 patients with virus hepatitis or liver damage followingparacetamol overdose who were ill enough to warrant hospitaladmission, but who did not develop fulminant hepatic failure. Electron microscopy of platelets from patients with fulminanthepatic failure showed many structural abnormalities includingnumerous pseudopods, vacuoles and blurred plasma membranes.Most striking were the numbers of platelets showing microtubules,and the increased microtubular content per platelet. As patientsrecovered from fulminant hepatic failure, platelet functionimproved and platelets with normal ultrastructure appeared amongstthe abnormal ones. The abnormal-looking platelets may be responsible for the abnormalitiesof platelet function, but kinetic studies are required to elucidatetheir source and fate.     

Cold agglutinin disease revealing mediastinal seminoma

Sir, Cold agglutinin disease (CAD) is an autoimmune haemolytic anaemiain which cold-reactive auto-antibodies bind to erythrocyte carbohydrateantigens, causing hemagglutination and complement-mediated haemolysis.^1–4It is associated with various conditions, including infections(Mycoplasma pneumoniae, hepatitis C), autoimmune diseases (especiallysystemic lupus erythematosus) and lymphoproliferative disorders(mainly lymphoma.^1–8 However, it has rarely been described