Immunological abnormalities in asymptomatic homosexual men: correlation with antibody to HTLV-III and sequential changes over two years

A prospective study on 100 homosexual male volunteers was designed to examine immunological function in relation to sexual activity and infection with the human T cell lymphotropic virus Type III (HTLV-III). Complete data were available for 71 men. In a comparison with 100 age-matched heterosexual men, the study group of 100 men had a significantly higher mean serum IgG level (12.1 +/- SD 2.7 g/l vs. 10.9 +/- 2.4 g/l, p less than 0.01) and a significantly lower mean number of CD4 (T4) cells (845 +/- 310 X 10(-6)/l vs. 1128 +/- 375; p less than 0.01). For the study group, seropositivity for anti-HTLV-III was present initially in 22 per cent and was associated with a higher mean level of serum IgG and lower mean number of CD4 cells. Among seropositive homosexual men a low CD4/8 ratio was attributable to low numbers of CD4 cells in those without lymphadenopathy and to high numbers of CD8 cells in those with lymphadenopathy. For the seronegative homosexual men, a low CD4/8 ratio as a result of an increased CD8 cell count was present in 12 of 60, and was associated with numerous sexual partners and semen culture positive for cytomegalovirus. In two seropositive subjects a low CD4/8 ratio due to a decrease in the CD4 cell count was predictive of the development of AIDS by some two years. For the 71 men with complete data over two years, indices of cell-mediated immunity, including mean counts of CD4 cells, the CD4/8 ratio, and score for recall of cutaneous delayed type hypersensitivity increased during the first year but not during the second year in both seropositive and seronegative subjects. These increases occurred in association with changes in sexual practices and activity, but could not be attributed to any one particular factor.     

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.     

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.     

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.     

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.     

Serum β2-microglobulin in intravenous drug users and its correlation with human immunodeficiency virus infectionin intravenous drug users and its correlation with human immunodeficiency virus infection

Summary High levels of serum β₂-microglobulin have been associated with human immunodeficiency virus infection and β₂-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of β₂-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum β₂-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4⁺ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum β₂-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of β₂-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of β₂-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.     

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.     

The Edinburgh City Hospital cohort: analysis of enrolment, progression and mortality by baseline covariates

We describe baseline characteristics, enrolment, progressionand mortality of the Edinburgh City Hospital HIV cohort. Therewere 431 men and 191 (31%) women; 439 (71%) infected via injectiondrug use (IDU); 92 (15%) via homosexual intercourse; 84 (13%)via heterosexual intercourse and 7 from blood products. Medianannual rate of CD4 cell loss was 49 (90% range: 15–146);Both homosexual men and patients aged >40 years at enrolmentlost CD4 cells significantly more quickly. In multifactorialanalysis controlled for baseline CD4 count and IgA, there wasno gender effect, but young patients (< 25 years) progressedsignificantly more slowly to AIDS (RR 0.4, p = 0.00). Homosexualmen progressed significantly more quickly than IDUs, with adjustedrelative risks (RR) of 2.9 (p=0.00), 2.5 (p=0.01) and 1.5 (p= 0.1) for progression to CDC stage IV, AIDS and death, respectively.The three-year survival rate post-AIDS was 25% (SE 4.3) andthere was no gender effect on survival. There was, however,an age effect whereby individuals diagnosed with AIDS in their40s or later showed poorer survival (RR 1.9, p = 0.04). Zidovudinetreatment after an AIDS diagnosis significantly lengthened post-AIDSsurvival (RR 0.5, p = 0.08).     

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.     

Tuberculosis in Patients Infected with Human Immunodeficiency Virus 1. A Retrospective Multicentre Study of 123 Cases in France

SUMMARY In order to study the epidemiological, clinical, and progressivecharacteristics of TB in HIV-infected individuals, a retrospectivestudy was conducted in nine infectious disease centres of universityhospitals located in the southern half of France. Among the5730 HIV-seropositive in- and out-patients, 123 (2.1 per cent)had TB (121 infections caused by M. tuberculosis, 2 by M. bovis).Tuberculosis was pulmonary in 53 patients (43.1 per cent), extrapulmonaryin 36 patients (29.3 per cent), and combined in 34 patients(27.6 per cent). There was no statistically significant differenceamong these three locations as to the mean CD4 count/mm³ (160±17),the type of antituberculosis therapy, the length of treatment(10.8±0.6 months) and the outcome. Fifty-two (45.2 percent) patients received an initial antituberculosis therapeuticregimen of four drugs: isoniazid, rifampicin, ethambutol, pyrazinamide;54 (46.9 per cent) were started on three drugs: isoniazid, rifampicin,ethambutol; and nine (7.8 per cent) received a two-drug combination:isoniazid, rifampicin. Fourteen of 75 patients subsequentlyreceived secondary preventive therapy. The mean follow-up timewas 252±290 days. Clinical healing was obtained in 57.7per cent of patients. Forty-six patients died, 33 during treatment:23 from AIDS and eight from TB (in the first 3 weeks of treatment).Five patients suffered from relapses due to poor treatment compliance.Patients had a good prognosis if tuberculosis was diagnosedearly.     

Frequency Analysis of Ventricular Fibrillation and Resuscitation Success

SUMMARY In 56 patients, frequency analysis of the electrocardiogramof ventricular fibrillation exhibited power spectra with a distinctdominant frequency. The greatest success for resuscitation fromventricular fibrillation is recorded when ventricular fibrillationdevelops after the patient comes under coronary care. Of the41 patients in whom the onset and first 8 s of ventricular fibrillationwere artefact-free the mean dominant frequency of primary ventricularfibrillation (no cardiogenic shock or cardiac failure) in 21patients was 6.2±0.2 Hz, significantly higher than themean dominant frequency of the first 8 s of secondary ventricularfibrillation (cardiogenic shock or heart failure) (4.0±0.2Hz, 20 patients, p =0.0001). In these patients the peak-to-troughamplitude (ECG) of the first 8 s of ventricular fibrillationwas similar in both primary and secondary ventricular fibrillationas was the mean duration of ventricular fibrillation prior tothe first DC shock. There was a significantly lower successrate for resuscitation from secondary ventricular fibrillation(6 of 20 patients) compared with resuscitation from primaryventricular fibrillation (18 of 21 patients, x² 17.8, p=0.001).Of the remaining 15 patients who were collapsed between 3 and20 min before the arrival of the mobile coronary care unit,the dominant frequency of the first 8 s of ventricular fibrillationfell with increased duration of collapse (from 5.5 Hz at 3 minto a mean of 2.1 Hz at 20 min). Four of these 15 patients whosurvived the initial arrest had a mean dominant frequency of5.2±0.3 Hz, which was significantly higher than the meandominant frequency (3.1±0.3 Hz, p<0.01) of the 11patients who were not resuscitated. This study shows that low frequency ventricular fibrillationis indicative of a poor chance of successful resuscitation.Alteration of the frequency may increase resuscitation success.     

Spontaneous Peritonitis in Cirrhotic Hospital In-patients: Retrospective Analysis of 101 Cases

One hundred and one patients with cirrhosis resulting from alcoholabuse, admitted to Broussais University Hospital, Paris, betweenJanuary, 1986 and December, 1989 were assessed for infectionof the ascitic fluid using clinical and cytobacteriologicalcriteria. All of 46 patients (45.5%) with clinical signs andsymptoms of peritonitis had an ascitic fluid polymorphonuclear(PMN) count > 250 cells/mm³. Bacteria could be isolated fromthe ascitic fluid of 23 patients (50%). Twenty-six bacterialstrains were isolated(there was more than one strain in twosamples). Escherichia coli was found in 14 cases. It is noteworthythat no anaerobes were grown. Mortality, biochemical parametersand clinical features correlated significantly with an asciticfluid PMN count > 250 cells/mm³. High mortality correlatedwith a PMN count > 1000 cells/mm³ (70% vs. 33%).     

Iron Metabolism in Haemodialysis Patients: A STUDY OF THE MANAGEMENT OF IRON THERAPY AND OVERLOAD

Some dialysis units replace iron losses in patients on maintenancehaemodialysis treatment (MHDT) with parenteral iron becauseof doubts about adequate intestinal iron absorption. Recentexperiences in Oxford indicate that this can lead to potentiallydangerous iron loading. Sixty-four of 120 MHDT patients hadserum ferritin levels >1000 µg/l and there was a goodcorrelation between these levels and the number of years ondialysis. A retrospective post-mortem study of 22 MHDT patientsshowed significant amounts of iron in liver and spleen and infive cases there was myocardial iron loading. Five MHDT patientswith iron loading were given desferrioxamine intravenously atdialysis. Iron was chelated but with some difficulty. Iron absorption, using ⁵⁹Fe and the total body counter, wasfound to be similar in both the MHDT patients with iron deficiency(mean ± S.E.M.; 42·5 ± 5·8 per cent)and iron deficient subjects without renal disease (45·3± 1·86 per cent). In iron replete MHDT patientsiron absorption (8·1 ± 2·6 per cent) didnot differ significantly from normal controls (14·9 ±1·6 per cent) while it was reduced in iron loaded MHDTpatients (5·4 ± 0·7 per cent). There wasa good correlation between red cell indices and iron storesin MHDT patients and haemoglobin values in 15 iron deficientMHDT patients rose significantly when treated with oral iron. These findings indicate that the control mechanisms which relateiron absorption to body iron stores are intact in patients onMHDT. Oral iron therapy is recommended and can be monitoredusing red cell indices. Prolonged parenteral iron treatmentis unnecessary and potentially dangerous.     

Haematological changes and infectious complications in anorexia nervosa: a case-control study

To determine the prevalence of haematological abnormalitiesin patients with anorexia nervosa (AN), and assess the relationshipsbetween these changes, the severity of AN and the propensityto infections, we retrospectively studied 67 patients who metthe DSM-III-R diagnostic criteria for AN. We recorded physicalfindings and routine haematological data on admission, and infectiousevents during hospitalization. The patients were compared with67 normal controls matched for age and sex. Mean haemoglobin(Hb) was normal but lower in AN patients than in controls (131± 1 9 vs. 137 + 11 g/l, p=0.03) and the prevalence ofanaemia (Hb<120 g/l) was higher in the AN group (27% vs.1.5%, p<0.0001). Patients had a lower leucocyte count (4.94+ 1.9 vs. 6.78 + 2.4 x10⁹/ l , p< 0.0001), and increasedprevalence of leucopenia ( < 4 x 10 ⁹ cells/l)(36% vs. 1.5%,p<0.0001), neutropenia (<1500x10⁶ cells/l)(17% vs. 0%,p=0.0015)and thrombocytopenia (<150x109 / l ) (10% vs. 0%, p = 0.03).Only 2 patients (3%) had pancytopenia, but 9/17 patients withanaemia (53%) also had leucopenia. There was a slight but significantcorrelation between body-mass index (BMI) and total leucocyte,neutrophil and red blood cell counts. Severe infectious complicationsoccurred in 9% of AN patients vs. 0% in controls (p = 0.01);they were more frequent with neutropenia (relative risk, 15.1:95% Cl, 10–20.2) or low (<12) BMI (relative risk, 11.6:95% Cl, 6.6–16.6) on admission. Compared with controls,AN patients thus had an increased prevalence of anaemia, leucopeniaand thrombocytopenia. The severity of AN, as assessed by BMI,correlated with leucocyte, neutrophil and red blood cell countsbut not with platelet count The risk for subsequently developingsevere infections was significantly increased when low BMI orneutropenia was found on admission.     

Pharmacokinetics and Clinical Toxicity of Quinine Overdosage: Lack of Efficacy of Techniques Intended to Enhance Elimination

We report clinical details in 16 cases of quinine poisoning.Plasma quinine concentrations above 15 mg/l were associatedwith increased risks of permanent visual damage and of cardiacarrhythmias from which one of our patients died. The rate ofquinine elimination was not significantly altered by forcedacid diuresis in five patients(t^1/2 25.1±SEM 4.6 h) ascompared to eight patients treated conservatively (t^1/226.5±SEM5.78 h). Neither urinary pH or flow rate correlated consistentlywith urinary quinine clearance. In three other patients charcoalcolumn haemoperfusion, haemodialysis and exchange transfusionwere performed. These were also ineffective in increasing quinineelimination. It is concluded that techniques advocated to increasequinine elimination are ineffective in the management of quininepoisoning.     

Acupuncture regulates leukocyte subpopulations in human peripheral blood

Acupuncture has recently been attracting more and more peoplethroughout the world as an alternative treatment, however littleis known about its physiological activities (i.e. immune system).We examined acupuncture both quantitatively and qualitativelyby measuring CD-positive cell counts and cytokine expressionlevels in the blood, to determine the activity of T cells, Bcells, macrophages and natural killer (NK) cells. Fifteen millilitersof peripheral blood obtained from 17 healthy volunteers aged21–51 years, were analyzed using flow cytometry beforeand after acupuncture treatment. There was a statistically significantincrease in the number of CD2⁺, CD4⁺, CD8⁺, CD11b⁺, CD16⁺, CD19⁺,CD56⁺ cells as well as IL-4, IL-1β and IFN- levels in thecells after acupuncture stimulation of meridian points. Theseobservations indicate that acupuncture may regulate the immunesystem and promote the activities of humoral and cellular immunityas well as NK cell activity. In this article, we discussed howacupuncture regulated leukocyte numbers and functions sincethey are considered to be potential indicators for evaluatingcomplementary and alternative medicine.     

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.     

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.     

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years(mean±SEM) with chronic renal failure of varied aetiologywere randomized to receive either a conventional low proteindiet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphatediet (providing approximately 1000 mg phosphate plus an orallyadministered phosphate binder, minimum protein intake 0.8 g/kg/day;n=30) or to control (minimum protein intake 0.8 g/kg/day, nophosphate restriction; n=32). Patients were reviewed for a minimumof 6 months before randomization and were withdrawn from thestudy if plasma creatinine exceeded 900 µmol/1, plasmaphosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an averageof 19±3 months. Mean plasma creatinine rose from 398±33to 600±50 µmol/1. Dietary protein intake was estimatedat 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05in the low phosphate and 1.14±0.05 in the controls, phosphateintake was 815±43, 1000± 47, and 1315±57mg/day, respectively. Urinary urea excretion and protein catabolicrates were significantly reduced (p<0.01) only in those onprotein restriction, at 213±9 mmol/24 hours and 0.71g/kg/day, respectively. Phosphate excretion was significantlylower (p<0.05) in both the low protein group (17.9±0.8mmol/24 hours) and the low phosphate group (18.6±1.0mmol/24 hours) compared to controls. Changes in body weight,muscle mass and serum transferrin, albumin and immunoglobulinswere comparable between the groups. Mean blood pressure followingrandomization was 150/89±3/1 (low protein), 148/87±3/1(low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall ofcreatinine clearance (ml/min/ 1.73 m²/month), by rate of deteriorationderived from reciprocal plasma creatinine against time plots(1/mmol/year) and to assess individual patient's response totreatment by two phase linear regression (‘breakpoint’)analysis of reciprocal plasma creatinine/time plots. Progressionwas analysed only in patients seen for at least 3 months followingrandomization. The rate of fall of creatinine clearance was not significantlydifferent between the groups (ANOVA): 0.56±0.08 ml/min/1.73m2/month (low protein, n=28), 0.44±0.07 (low phosphate,n=23) and 0.69±0.11 (control, n=27). In 50 patients (18low protein, 16 low phosphate and 16 control) whose rate ofprogression could be calculated before and after randomization,there was a fall in rate of progression averaging 0.18 ml/min/1.73m2/month in those on low protein diet and those on low phosphatediet, but a rise of 0.08 in the controls. These differenceswere, however, not statistically significant. Similar resultswere obtained when the rates of deterioration were calculatedfrom plasma creatinine. Significant individual improvements(p<0.01) in rates of progression by ‘breakpoint’analysis occurred in 17 patients: six on low protein, sevenon low phosphate and in four controls. Sixty-one (72 per cent)of the patients examined by this method showed no significantchange in the rate of progression while seven patients had acceleratedprogression. There was no difference in the requirement formaintenance dialysis facilities between groups. No significant benefit of protein and phosphate restrictionwas therefore demonstrated.     

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