Review of Soft Tissue Masses of the Foot and Ankle: Magnetic Resonance Imaging Features.

A large number of soft tissue masses affect the foot and ankle, with the majority being benign. Benign and malignant soft tissue lesions usually present as lumps, and it is important to differentiate between them to allow for optimal management. Imaging, in particular magnetic resonance imaging (MRI), can contribute to narrow the differential diagnosis of soft tissue masses of the foot and ankle by describing its exact location, internal signal characteristics, presence of enhancement, and its relation to adjacent structures. In this review, we review the literature to describe the most common soft tissue masses around the foot and ankle, focusing on the MRI features of the lesions.

Intermittent Superior Vena Cava Syndrome Secondary to Malignant Pericardial Mesothelioma.

Malignant pericardial sarcomatoid mesothelioma is a massively rare tumor accounting for 0.8% of all cases of mesothelioma. Superior vena cava syndrome (SVCS) occurs due to a partial obstruction or compression to the superior vena cava, which hinders the blood outflow to the upper body. It can be caused by an intrinsic factor such as thrombosis, or by an extrinsic factor such as tumors. Clinical presentation includes edema of the face and upper limbs, plethora, dyspnea, dysphagia, stridor and cough. we are reporting a case of a 56-year-old female, who is a known case of hypertension on angiotensin-converting enzyme inhibitors (ACEIs). Presented to the emergency department with intermittent facial swelling and dyspnea. Imaging and pathology reports confirmed the diagnosis of intermittent SVCS secondary to pericardial sarcomatoid mesothelioma with pericardial effusion. What makes our case unique is that both the etiology and the presenting complaint are rare entities, as most SVCS cases are continuously symptomatic throughout the disease course, and are usually caused by a lung cancer or lymphoma.

Efficacy and safety assessment of expiratory positive airway pressure (EPAP) mask for OSAHS therapy.

OBJECTIVE: We have designed the expiratory positive airway pressure (EPAP) mask to provide a new sort of therapeutic strategies for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). And this study aims to assess the safety, efficacy and compliance of the EPAP therapy. METHODS: 40 healthy volunteers were enrolled to measure the end-tidal carbon dioxide pressure (PETCO2) while being treated by EPAP mask. 40 symptomatic moderate or severe OSAHS patients (AHI≥15/h) recruited were equally divided into two groups randomly and treated with CPAP or mask for a week respectively. After a week of washing out, the patients were applied with exchanged therapeutic methods for another week. The PSG was performed at the end of each week of treatment with device-on. RESULTS: There were no significant differences of PETCO2 under different exhaled positive pressure level between CPAP, EPAP therapies and non-therapy for the healthy volunteers (P>0.05). After being treated, among the OSAHS patients in the two groups, the ESS scores and AHI decreased, and minimum SaO2 and mean SaO2 increased significantly (all P>0.05). There was no significant differences of the efficacy between EPAP and CPAP therapy. CONCLUSIONS: EPAP mask therapy was safe and reliable with significant efficacy for selected OSAHS patients. However, the compliance needs further improvement.

Early-onset Streptomyces endocarditis in a prosthetic aortic valve.

A 66-year-old Australian man underwent elective replacement of a severely stenotic aortic valve with a 22-mm Medtronic-Hall valve. Six weeks later, he was readmitted with worsening dyspnea, fever, and mild anemia. Investigations confirmed pulmonary edema and moderate periprosthetic aortic regurgitation. The pulmonary edema was managed conservatively, and a second 22-mm Medtronic-Hall valve was implanted. Infective endocarditis was suspected in the aortic annulus below the orifice of the right coronary artery. A bacteriological study revealed a rare bacteria of Streptomyces species. The patient received intensive antibiotic therapy over a 6-week period of hospitalization, and the aortic regurgitation disappeared one week postoperatively.

The role of esophageal stent placement in the management of postesophagectomy anastomotic leak.

BACKGROUND/AIM: Anastomotic leak after esophagectomy is one of the most challenging complications resulting in a high morbidity and mortality and prolonged hospitalization. The study intended to assess the outcome of endoluminal self-expanding stent in the treatment of this problem. SETTINGS AND DESIGN: Department of Thoracic and Cardiovascular Surgery, Arhus University Hospital, Skejby, Arhus, Denmark. A retrospective study. PATIENTS AND METHODS: From January 2007 to December 2010, 209 patients underwent esophagectomy for malignant disease of the esophagus or the cardia. Twenty patients developed anastomotic leak. Treatment consisted of conservative measures, surgery, and stent placement. Details of treatment, clinical outcome, complications, and mortality were evaluated. STATISTICAL ANALYSIS: None. RESULTS: One hundred and forty-seven patients (70.3%) had carcinoma of the cardia, whereas 62 patients (29.7%) had esophageal carcinoma. Twenty patients (9.5%) developed anastomotic leak; small (<1 cm) in two patients (10%); managed conservatively and bigger than 1 cm in 15 patients (75%); treated with an esophageal stent (Hanaro stent, DIAGMED Healthcare, Thirsk, YO7 3TD, United Kingdom). In three patients (15%), perforation of the staple line of the intrathoracic gastric conduit was found and managed by reoperation. Functional sealing of anastomoses after stent placement could be achieved in 10 patients (67%). Stent-related morbidity developed in five patients (33%): Migration of the stent, n=3 and tracheoesophageal fistula, n=2. Stents were smoothly removed 3 weeks after discharge. The mean hospital stay was 25 days. There was only one stent-related death (6.6%). CONCLUSION: Endoluminal stent implantation is an effective and safe option in the management of postesophagectomy leaks.

Viewpoint: scaling up testing services for non-communicable diseases in Africa: priorities for implementation research.

The burden of non-communicable diseases in Africa is rising rapidly and implementation of evidence-based control strategies is needed urgently. Testing people for hypertension and diabetes will be an important component in the fight against these diseases, as voluntary counselling and testing was for HIV-infection. We discuss the below the areas where we believe evidence is needed to inform policy.

The experience of "medicine companions" to support adherence to antiretroviral therapy: quantitative and qualitative data from a trial population in Uganda.

Good adherence is critical for antiretroviral therapy (ART) in sub-Saharan Africa. We report on the characteristics of medicine companions (MCs) chosen by Ugandan patients enrolling on ART, and on how MCs were chosen, and what roles they played. Baseline data on MCs of 1453 participants in a randomized controlled trial comparing facility and home-based delivery of ART in Jinja, Uganda were analyzed. Textual data on experience with MCs were collected through in-depth interviews among a subsample of 40 trial participants equally divided by sex and trial arm. Significantly more women (71%) than men (29%) were recruited. The majority (75%) of women participants were either widowed (51%) or separated or divorced (24%), whereas most of the men (66%) were married. Women were most likely to choose a child as their MC while men were most likely to choose their spouse; 41% of women chose an MC under 21 compared with only 14% of men. Only 31% of married women chose their husband, compared with 66% of married men who chose their wife. Qualitative interviews suggested MCs proved useful for reminding and other supportive tasks in the first three months but were generally less essential by six months and beyond. Convenience, reliability, and trust were key considerations in choosing an MC. Children provided the only alternative for many unmarried women, but even some married women felt children made more reliable MCs than husbands. Participants who had disclosed their serostatus usually received drug-taking reminders from multiple household members. One participant in the qualitative sample with poor family relations delayed starting treatment due to unwillingness to identify an MC. MCs were generally welcome and useful in supporting early adherence. However, disclosure to an MC should not be a condition of obtaining treatment.

Increased risk of HIV-infection among school-attending orphans in rural Zimbabwe.

In Zimbabwe around 1.1 million children have been orphaned due to AIDS. We conducted a survey among school-attending youth in rural south-eastern Zimbabwe in 2003, and examined the association between orphaning and risk of HIV. We enrolled 30 communities in three provinces. All students attending Year 2 of secondary school were eligible. Each completed a questionnaire and provided a finger-prick blood specimen for testing for HIV-1 and HSV-2 antibodies. Female participants were tested for pregnancy. Six thousand seven hundred and ninety-one participants were recruited (87% of eligible); 35% had lost one or both parents (20% of participants had lost their father; 6% their mother; and 9% both parents). Orphans were not poorer than non-orphans based on reported access to income, household structure and ownership of assets. There was strong evidence that orphans, and particularly those who had lost both parents, were at increased sexual risk, being more likely to have experienced early sexual debut; to have been forced to have sex; and less likely to have used condoms. Fifty-one students were HIV positive (0.75%). Orphans were three times more likely to be HIV infected than non-orphans (adjusted odds ratio = 3.4; 95% confidence interval: 1.8-6.6). Over 60% of those HIV positive were orphaned. Among school-going youth, the rates of orphaning were very high; there was a strong association between orphaning and increased risk of HIV, and evidence of greater sexual risk taking among orphans. It is essential that we understand the mechanisms by which orphaned children are at increased risk of HIV in order to target prevention and support appropriately.

Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application.

Remote ischemic conditioning is a novel concept of protection against ischemia-reperfusion injury. Brief controlled episodes of intermittent ischemia of the arm or leg may confer a powerful systemic protection against prolonged ischemia in a distant organ. This conditioning phenomenon is clinically applicable and can be performed before--preconditioning, during--perconditioning, or after--postconditioning prolonged distant organ ischemia. The remote ischemic conditioning may have an immense impact on clinical practice in the near future.

High Levels of Psychosocial Readiness for ART in an African population at the Onset of Treatment

Adherence at the earliest stages of treatment is likely to be influenced by prior illness trajectories and future expectations; best captured (and addressed) before treatment begins. We examined the influence of illness trajectories and treatment expectations on psychosocial readiness to start antiretroviral therapy (ART) in Jinja; Uganda. In-depth interviews were conducted between October 2005 and April 2006 with 41 members of an AIDS support organisation on their first day of treatment. Transcribed texts were translated; coded and analysed thematically using NVIVO-7 software. Results indicated that acute fear of death and progressive withdrawal from social; economic and sexual roles narrowed focus on survival; while efficacy-enhancing experiences with septrin prophylaxis and trust in counsellors reinforced belief in HIV diagnosis and importance of adherence. Most enjoyed supportive home environments after disclosing their serostatus. Lack of money for food and transport was anticipated as the main barriers to future adherence; particularly among women. Integrating strong counselling support with ART provision helped channel the power of shared illness experience into positive motivation to adhere at the onset of treatment

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.

OBJECTIVES: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers. METHODS: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women. RESULTS: All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced. CONCLUSION: Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0 microg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09 microg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3 microg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious.

Infant morbidity in an Indian slum birth cohort.

OBJECTIVE: To establish incidence rates, clinic referrals, hospitalisations, mortality rates and baseline determinants of morbidity among infants in an Indian slum. DESIGN: A community-based birth cohort with twice-weekly surveillance. SETTING: Vellore, South India. SUBJECTS: 452 newborns recruited over 18 months, followed through infancy. MAIN OUTCOME MEASURES: Incidence rates of gastrointestinal illness, respiratory illness, undifferentiated fever, other infections and non-infectious morbidity; rates of community-based diagnoses, clinic visits and hospitalisation; and rate ratios of baseline factors for morbidity. RESULTS: Infants experienced 12 episodes (95% confidence interval (CI) 11 to 13) of illness, spending about one fifth of their infancy with an illness. Respiratory and gastrointestinal symptoms were most common with incidence rates (95% CI) of 7.4 (6.9 to 7.9) and 3.6 (3.3 to 3.9) episodes per child-year. Factors independently associated with a higher incidence of respiratory and gastrointestinal illness were age (3-5 months), male sex, cold/wet season and household involved in beedi work. The rate (95% CI) of hospitalisation, mainly for respiratory and gastrointestinal illness, was 0.28 (0.22 to 0.35) per child-year. CONCLUSIONS: The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory and gastrointestinal illnesses. The risk factors identified were younger age, male sex, cold/wet season and household involvement in beedi work.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial.

BACKGROUND: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. METHODS: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. FINDINGS: CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7) (n=300) at day 7). INTERPRETATION: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.

Acute lower respiratory infections among children hospitalized in Bangui, Central African Republic: toward a new case-management algorithm.

To measure the performance of the current WHO algorithm in identifying children at higher risk of death, children aged 2-59 months who presented with cough and/or difficult breathing and were admitted into the paediatric hospital of Bangui (Central African Republic) during a 1-year period (1996/97) were investigated. Among children with subcostal indrawing, mortality and severity of oxygen desaturation were identical whether or not they also had tachypnoea. Among children with a 'severe pneumonia', those who also fulfilled the 'very severe disease' definition had a higher risk of death (31/132, 23.5%) than those who did not (12/106, 11.3%, P = 0.02). However, this 'very severe disease' definition did not predict death when used in children who did not have severe pneumonia. To identify variables that would better predict death, combinations of symptoms and signs were examined among the subgroup of children with indrawing. Nine combinations had both a sensitivity and specificity over 60%. 'Grunting and/or nasal flaring' had a sensitivity of 72% and a specificity of 66% in predicting death, and might be easier to use by primary health care personnel than other combinations. A new algorithm is proposed for the management of children aged 2-59 months presenting with cough and/or difficult breathing. The definition of pneumonia would be unchanged (tachypnoea). Severe pneumonia would remain defined on indrawing regardless of respiratory rate, except that indrawing should be lower chest wall and/or intercostal. In health facilities where intravenous antibiotics, chloramphenicol and/or oxygen are available, entry into a 'very severe pneumonia' category would be based on 'grunting and/or nasal flaring' among children with indrawing. In our study population, the mortality rates in the categories based on these definitions were 0.8% (1/127) in children with no pneumonia, 0.9% (1/116) in children with pneumonia, 7.7% (12/156) in children with severe pneumonia and 31.1% (33/106) in children with very severe pneumonia.

Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway.

Cholinergic basal forebrain (CBF) projection systems are defective in late Alzheimer's disease (AD). We examined the brains of 12-month-old singly and doubly transgenic mice overexpressing mutant amyloid precursor protein (APP(swe)) and/or presenilin-1 (PS1(M146L)) to investigate the effects of these AD-related genes on plaque and tangle pathology, astrocytic expression, and the CBF projection system. Two types of beta-amyloid (Abeta)-immunoreactive (ir) plaques were observed: type 1 were darkly stained oval and elongated deposits of Abeta, and type 2 were diffuse plaques containing amyloid fibrils. APP(swe) and PS1(M146L) mouse brains contained some type 1 plaques, while the doubly transgenic (APP(swe)/PS1(M146L)) mice displayed a greater abundance of types 1 and 2 plaques. Sections immunostained for the p75 NGF receptor (p75(NTR)) revealed circular patches scattered throughout the cortex and hippocampus of the APP(swe)/PS1(M146L) mice that contained Abeta, were innervated by p75(NTR)-ir neurites, but displayed virtually no immunopositive neurons. Tau pathology was not seen in any transgenic genotype, although a massive glial response occurred in the APP(swe)/PS1(M146L) mice associated with amyloid plaques. Stereology revealed a significant increase in p75(NTR)-ir medial septal neurons in the APP(swe) and PS1(M146L) singly transgenic mice compared to the APP(swe)/PS1(M146L) mice. No differences in size or optical density of p75(NTR)-ir neurons were observed in these three mutants. p75(NTR)-ir fibers in hippocampus and cortex were more pronounced in the APP(swe) and PS1(M146L) mice, while the APP(swe)/PS1(M146L) mice showed the least p75(NTR)-ir fiber staining. These findings suggest a neurotrophic role for mutant APP and PS1 upon cholinergic hippocampal projection neurons at 12 months of age.

Environmental risk factors for clinical malaria: a case-control study in the Grau region of Peru.

The role of environmental risk factors in clinical malaria has been studied mainly in Africa and Asia, few investigations have been carried out in Latin America. Field observations in northern coastal Peru, where the prevalence of malaria is high during the agricultural season, suggested that the risk of disease varied according to the characteristics of the house and the house environment. Environmental determinants of the risk of clinical malaria were therefore investigated through a case-control study: 323 clinical cases of malaria, recruited through community-based active case-finding, and 969 age-, sex- and village-matched controls were recruited into the study over a period of 12 months ending June 1997. Residual spraying of houses in the previous 6 months, living more than 100 m from a canal, a level of education equal to primary school or above and working in agriculture conferred significant protection from the risk of developing clinical malaria. The presence of spaces between the wall and roof in the subject's bedroom (eaves) and a house aged > 4 years statistically significantly increased the risk of disease. Based on these results we discuss possible control measures for malaria in this area of the country.

Evaluation of clinical pallor in the identification and treatment of children with moderate and severe anaemia.

BACKGROUND: Anaemia from malaria is a common problem in developing countries. Blood transfusion in developing countries is available in few hospitals. Children who are severely anaemic and may require urgent blood transfusion usually present to peripheral first-level health facilities from where they must be referred to hospitals. Since most peripheral facilities do not determine haemoglobin levels, the decision on referral has to be made on clinical grounds. OBJECTIVES: To evaluate the sensitivity and specificity of clinical pallor of the palms, nailbeds, conjunctivae, buccal mucosa or tongue against haemoglobin values and their reproducibility among health workers. METHODS: A total of 2540 children 2 months to 5 years of age presenting to a rural health centre in Ethiopia were enrolled. Clinically detected pallor was compared with measured blood haemoglobin concentrations. RESULTS: Any anaemia (haemoglobin < 11 g/dl) was found in 61% of the children. Severe anaemia (haemoglobin < 5 g/dl) was found in 4%. The presence of any pallor clinically correlated with moderate anaemia (haemoglobin level < 8 g/dl) could be detected with a sensitivity of 95% and a specificity of 64-68% when the palm and nailbeds were used and a sensitivity of 84% and a specificity of 81% when the conjunctivae were used. Severe anaemia was detected clinically as severe pallor in 50-56% of cases (with a specificity of 95-96%). Agreement between physicians was highest for conjunctivae and nailbed pallor (87%) and lowest for palm pallor (73%). Using multivariate analysis, identification of a systolic ejection murmur or altered sensorium, the presence of splenomegaly or malarial parasitaemia were independently predictive of severe and moderately severe anaemia. CONCLUSIONS: Moderate and severe anaemia can be identified clinically in most cases for treatment and referral purposes. A systolic ejection murmur, altered sensorium, the presence of splenomegaly or malarial parasitaemia may be used as additional tools in considering urgent referral for blood transfusion.

Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease.

Recent studies indicate that there is a marked reduction in trkA-containing nucleus basalis neurons in end-stage Alzheimer's disease (AD). We used unbiased stereological counting procedures to determine whether these changes extend to individuals with mild cognitive impairment (MCI) without dementia from a cohort of people enrolled in the Religious Orders Study. Thirty people (average age 84.7 years) came to autopsy. All individuals were cognitively tested within 12 months of death (average MMSE 24.2). Clinically, 9 had no cognitive impairment (NCI), 12 were categorized with MCI, and 9 had probable AD The average number of trkA-immunoreactive neurons in persons with NCI was 196, 632 +/- 12,093 (n = 9), for those with MCI it was 106,110 +/- 14,565, and for those with AD it was 86,978 +/- 12,141. Multiple comparisons showed that both those with MCI and those with AD had significant loss in the number of trkA-containing neurons compared to those with NCI (46% decrease for MCI, 56% for AD). An analysis of variance revealed that the total number of neurons containing trkA immunoreactivity was related to diagnostic classification (P < 0.001), with a significant reduction in AD and MCI compared to NCI but without a significant difference between MCI and AD. Cell density was similarly related to diagnostic classification (P < 0.001). There was a significant correlation with the Boston Naming Test and with a global score measure of cognitive function. The number of trkA-immunoreactive neurons was not correlated with MMSE, age at death, education, apolipoprotein E allele status, gender, or Braak score. These data indicate that alterations in the number of nucleus basalis neurons containing trkA immunoreactivity occurs early and are not accelerated from the transition from MCI to mild AD.