Aspects des complications ostéoarticulaires de la drépanocytose en scintigraphie osseuse planaire (infection exclue). À propos de trois observations

Skeletal complications of sickle-cell anemia are multiple and can appear on the acute (osseous infarction, acute osteomyelitis) or chronic mode (osteonecrosis, chronic osteomyelitis). The radio-labelled diphosphonates bone scintigraphy remains an important tool in the early diagnosis and in the follow-up of these complications and must form part of the initial assessment of the disease. Through clinical observations, the authors undertake to sum up the bone scintigraphy aspects of these complications.     

A benign sickle-cell disease in a Saudi subject with beta zero-thalassemia and glucose-6-phosphate dehydrogenase deficiency

Sickle-cell disease with raised fetal hemoglobin is found relatively frequently in the eastern part of the Arabian Peninsula. In contrast to the severe and sometimes life-threatening complications of sickle-cell disease in the black population, Saudi Arabs homozygotes for HbS gene exhibit a mild course for this disease. Here we present a Saudi sickle-cell patient with an unusually low fetal hemoglobin level. Moreover, this individual has beta 0-thalassemia and a deficiency in the enzyme glucose-6-phosphate dehydrogenase. Clinical and hematological examinations revealed a remarkably benign condition. This observation is potentially important since most of the mild clinical symptoms of sickle-cell disease have been attributed to high fetal hemoglobin. Clearly in this case, other factors are operating and may be also operating in those patients with high fetal hemoglobin.     

Nouvelle stratégie dans le diagnostic,la prévention et le suivi de l’ostéonécrose drépanocytaire en Côte d’Ivoire à partir de la scintigraphie osseuse

Osteonecrosis is the most frequent complications of sickle-cell disease (SCD) whose prevalence in Côte d’Ivoire is 21%. The main of this study was to compare scintigraphy, clinical and radiological observations to assess earlier diagnosis in SCD osteonecrosis. It was a prospective study about 45 SCD patients who presented coxopathy and had radio-labelled diphosphonates bone scintigraphy. The results revealed 49% of lesions whose 48% appeared wiyh homogeneous hyperfixation, 11% homogeneous hypofixation, 5% of hypofixation contourned by hyperfixation. Eighty-one percent of lesions concerned femoral head, 6% femoral condyle and 3% humoral head. Fifty percent of osteonecrosis was not visible in radiology and corresponded to the earlier stade. These invisible radiology aspects were observed in 100% hips without lameness, and in 43% permanent lameness. Scintigraphy (sensitive in 100%) isolated 38% more than conventional radiography. In main to improve SCD osteonecrosis prognostic in Côte d’Ivoire, this preliminary study outline that scintigraphy is fundamental in management.     

Cytokines in Gaucher's disease.

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.     

Sickle-cell Anaemia,Sickle-cell Thalassaemia,Sickle-cell Haemoglobin C Disease,and Asymptomatic Haemoglobin C Thalassaemia in one Ghanaian Family

A Ghanaian family is described in which a sickle-cell haemoglobin C man married to a sickle-cell thalassaemia woman produced 12 children (eight alive). Four children have sickle-cell anaemia, two sickle-cell haemoglobin C disease, one has sickle-cell thalassaemia, and one is asymptomatic haemoglobin C thalassaemia.It is emphasized that the contribution that adult sickle-cell disease patients make, through procreation, to the persistence of the S gene may be greater than is normally supposed, and that this contribution may soon outstrip that made by balanced polymorphism through falciparum malaria. Widespread haemoglobin genotyping in schools leading to genetic counselling is advocated to decrease the incidence of sickle-cell disease.     

Quantitative aspects of the relationship between the sickle-cell gene and malaria

The relationship between resistance to Plasmodium falciparum infection and the frequency and distribution of the sickle-cell gene in populations exposed to endemic malaria transmission is reducible to clear and quantifiable terms. In this review, Trevor Jones examines the prediction of gene frequency changes under selective pressure, the selective advantage to the heterozygote (balanced polymorphism) that the sickle-cell gene provides to individuals in areas with malaria transmission, and the relationship between sickle-cell gene frequency and malaria, as measured by, for example, sporozoite rate and basic reproduction rate. He seeks to clarify what one can infer about malaria transmission from an analysis of the distribution and inheritance patterns of the sickle-cell gene and sickle-cell disease and under what circumstances these inferences should be made.     

Canine babesiosis in Europe: how many diseases?

Babesiosis, recognized since ancient times as an important disease of livestock and more recently as an emerging disease in dogs worldwide, is caused by intraerythrocytic protozoa of the genus Babesia and is transmitted by ticks. The pathophysiology of canine babesiosis has been extensively studied but many questions remain unanswered, especially regarding the diversity of disease manifestations in different European countries. Continued investigation of the similarities and differences in host-parasite interplay in canine babesiosis in different European countries should lead to a better understanding of the disease process, potentially leading to better prediction of disease outcome and the development of new treatment modalities. From the European point of view it is important to conduct these studies on Babesia canis.     

Anaesthesia in Sickle-cell States: A Plea for Simplicity

505 patients with various haemoglobinopathies were given a general anaesthetic between January 1970 and February 1972. One patient with haemoglobin SC disease and one patient with sickle-cell trait (HbAS) died postoperatively. Four other patients who were sickling positive, but whose genotypes were unknown, died, one from sickle-cell crisis precipitated by haemorrhage.A simple anaesthetic technique together with good postoperative care can provide safe general anaesthesia for patients with sickle-cell states. A plea is made for simplicity in the anaesthetic management of these patients.     

Protection afforded by sickle-cell trait (Hb AS): what happens when malarial selection pressures are alleviated?

A study of reproductive outcome in Mobile, AL was conducted among a large maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births among Hb AS women were significantly higher than among Hb AA women. These findings were surprising since it is generally held that once malarial pressure is alleviated, any reproductive advantage that might be conferred by Hb AS would disappear and fertility levels would reach levels similar to or slightly less than that of Hb AA women. A search of the literature was subsequently conducted and a large cohort study of an African-derived population was found in the United Kingdom. Results from this study also showed that parity was significantly higher among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS and Hb SS women, findings from these two studies raise doubts whether directional selection is occurring against the Rb S allele in nonmalarial environments. Balancing selection may still be occurring.     

The Sickle-cell and Altitude

High altitude seemed to be responsible for seven recent cases of sickling crisis. People with sickle-cell trait are at risk if they fly in unpressurized aircraft, which are used for many local air services. Those with sickle-cell haemoglobin C disease should avoid air travel even in pressurized aircraft. Possibly as a result of “autosplenectomy,” patients with sickle-cell anaemia seem to be able to fly in pressurized aircraft with little risk. All passengers and aircrew who might have some form of sickle-cell disease should be screened before flight.     

Survey of sickle-cell disease in England and Wales.

The incidence and the clinical course of patients suffering from sickle-cell syndrome (Hb SS; Hb SC; Hb S thal) in England and Wales are not known. In 1979 an ad hoc committee was formed to investigate these problems. Initially, a questionnaire was sent to 227 haematologists in England and Wales to determine the number of cases in these countries. The replies have indicated that 1367 cases were seen in 1978 and 1979. Probably this may represent only half the total number of cases. From this survey it has been possible to draw up a composite map showing the location of patients, which has provided a basis to determine the clinical course of the disease, and for further studies into the complications and management of sickle-cell disease in England and Wales. From a second questionnaire preliminary data about the general management and mortality in England and Wales have been recorded.     

Heterogeneity of sickle-cell anemia based on a profile of hematological variables.

Factors that influence the heterogeneity of the disease expression of sickle-cell anemia are not well understood. This study examines the ability of a profile of six hematological variables (HB, HCT, RBC, %Hb F, MCV, and %HBA2) to predict the severity of disease measured on 225 patients ranging from 0.2 to 18 years of age. Four subgroups of patients were identified separately in each sex using cluster analysis techniques. In each sex, mean hemoglobin concentration and percent Hb F increased across the four clusters from 7 to 10 gm/dl and from 7% to 16%, respectively. Mean cell volumes were approximately 90, 80, 90, and 75 in groups 1, 2, 3, and 4, respectively; thus MCV did not increase in an orderly progression along with HB and %Hb F. We studied the distribution of four anthropometric, five physical examination, and seven clinical measures of disease severity among clusters. In each sex, subgroups differed significantly (P less than .05) for percent ever hospitalized for sickle-cell anemia, percent ever transfused, and percent with bone-age delays greater than 1 year. In addition, male clusters differed significantly for percent ever having had pneumonia, priapism, or dactylitis, and females differed significantly for height and weight. %Hb F and its inverse relationship with %HBA2 was more highly associated with the measures of severity than the degree of anemia or MCV. This study establishes the utility of a vector of hematological variables as a predictor of heterogeneity of measures of clinical manifestations among young patients with sickle-cell anemia. The role of alpha-thalassemia and genetic factors that affect Hb F levels were considered as possible explanations for the observed heterogeneity.     

Indices of Metabolic Dysfunction and Oxidative Stress

Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake meaning that general diet is an important factor to take in account. Moreover, atrophy in the vasculature and a reduced glucose transporter activity for the vessels is also a common feature in Alzheimer disease. Finally, the overall size of neurons is larger in cases of Alzheimer disease than that of age-matched controls and, in individuals with Alzheimer disease, neuronal size inversely correlates with disease duration and positively associates with oxidative stress. Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology. Special issue dedicated to John P. Blass. Gemma Casadesus and Paula I. Moreira contributed equally to this paper. Aspects of this paper were previously presented in Neurochemical Research 28, 1549–1552, 2003 and the Journal of Alzheimer’s Disease 1, 203–206, 1999 and were used here with permission.     

Myasthenia gravis: pathophysiology,diagnosis, differential diagnosis and management

Myasthenia gravis is an autoimmune disorder caused by impaired synaptic transmission at the neuromuscular junction. The characteristic signs and symptoms of this disease manifest as increasing muscle fatigue. This article reviews myasthenia gravis with an emphasis on the pathophysiology, systemic and ocular manifestations, diagnostic testing, and management of this disease.     

Erythropoietin and renal function in sickle-cell disease.

The relation between haemoglobin concentration, creatinine clearance, and the serum concentration of erythropoiesis-stimulating factor were assessed in 31 patients with homozygous sickle-cell disease. Haemoglobin concentrations fell significantly with decreasing creatinine clearance (r = 0.58, p less than 0.001) and were positively correlated with the concentration of erythropoiesis-stimulating factor (r = 0.65, p less than 0.001). These observations suggest that erythropoietin concentration is the factor limiting production of red cells in sickle-cell disease with renal insufficiency and have implications for treatment.     

The pathophysiology of severe falciparum malaria

By the end of the 1940s, the clinical and pathological features of severe falciparum malaria had been well described by military physicians and pathologists working in theatres of war where the disease was endemic. From that time serious efforts were made to discover the pathophysiology of the severe manifestations of malaria because an understanding of these mechanisms forms an important basis for the clinical management of affected patients. Recently, after a period of neglect, there has been a revival of interest in malaria as a subject for clinical and laboratory research. In this article, Rodney Phillips and David Warrell review aspects of that work and attempt to unravel the mysteries of the pathophysiology of severe malaria in man.     

Sickle-cell disease in a British urban community.

Seventy cases of sickle-cell disease were identified in the London Borough of Brent from records dating back to 1962. All but three were still alive and, with one exception, were recalled for confirmation of the diagnosis and to provide personal and family histories. The group consisted of 22 individuals with homozygous sickle-cell anaemia (Hb SS), 12 with sickle-cell/beta-thalassaemia double heterozygosity, 34 with sickle-cell/haemoglobin C disease (Hb SC), and two with the combination of haemoglobin S and hereditary persistence of fetal haemoglobin. They were predominantly of West Indian origin, more than half had been born in Britain, and most were aged under 25. The records for 304 patient admissions between 1962 and 1979 were analysed. There were 199 sickle-cell-disease-related admissions, 61 unrelated to sickle-cell disease, and 44 for pregnancy or its complications. Admissions per patient-year averaged less than one, except for children with Hb SS under the age of 5 years, who were admitted more frequently. The commonest reasons for admission were painful crises (74% of all admissions) and the "chest syndrome" (21%). There were four pneumococcal infections, all in children with Hb SS under the age of 8 years; all recovered. Three patients, aged 10, 15, and 50 years, died. The two children with Hb SS died in their sleep without gross evidence of sickling at necropsy. Multiple brain infarcts were found at necropsy in the 50-year-old woman with Hb SC who, having survived nine uneventful pregnancies, succumbed to an infection after cryosurgery to the cervix. Obstetric records were available for 18 term pregnancies in 11 women. Three antenatal sickling crises and three postpartum thromboembolic complications were encountered. There were no maternal or perinatal deaths. Fifteen asymptomatic individuals with sickle-cell disease were diagnosed as a result of routine screening procedures. There are likely to be many such individuals currently undiagnosed in the community. They urgently need identification because of their increased risks from pregnancy, surgery, and infection.     

Severe malaria: metabolic complications

Metabolic complications of severe malaria are some of the most important and potentially treatable manifestations of this deadly disease. The commonest metabolic complications (lactic acidosis and hypoglycaemia) arise from increased host anaerobic metabolism probably due to a mismatch between tissue oxygen supply and requirement. Optimising treatments for these complications should be guided by detailed understanding of their underlying pathophysiology, and may help to reduce the intolerably high case fatality rate of severe malaria.     

ANR Inforare : proposition d’un modèle d’identifiant patient individuel pour les patients drépanocytaires

The main objective of INFORARE project is to organize the gathering, assessment and sharing of medical information between sickle-cell anaemia patient and the health workforce. The method is based on the: evaluation of the sickle-cell anaemia patients’ acceptability of the familial data collection; centralised management of medical files which have been rendered anonymous; proposition of an identification model for sickle-cell anaemia patients and the evaluation of first the feasibility of the identification data collection, second the data linkage quality.ResultsSemi-directive interview method undertaken by LEM permitted to interview 43 patients, six association members, and six health workforce personals regarding acceptability of the familial data collection. The informatics platform ensuring the centralised management of sickle-cell anaemia patients’ medical files has been very appreciated by clinicians. The familial component identification model contains anonymous identification data of patients and their parents. Due to data collection difficulties of 692 included patients, this familial component identification model cannot be implemented in terms of linking sickle-cell anaemia patient data with her/his family data.Discussion and conclusionThe information system model for sickle-cell anaemia disease should be extended to other rare diseases which need to organize the federation and sharing of medical information among patients, the health workforce, and patients’ families. The convivial application contains very useful data for clinical, biological and epidemiological studies, thus facilitates the relationship with other research programmes. Taking into account the familial dimension of the information will increase the potential knowledge extraction and utilization of genetic and multifactorial diseases.     

General anaesthesia in sickle-cell disease.

General anaesthesia was administered on 284 occasions to 200 patients with sickle-cell disease at one hospital during July 1958 to June 1978. No intraoperative but six postoperative deaths occurred. The management of anaesthesia may have contributed to two of the postoperative deaths. Clinically uneventful anaesthesia did not appear to provoke severe sickling crises or to be responsible for mortality, but a contribution to postoperative morbidity could not be excluded. A simple, careful anaesthetic technique and selective but not routine blood transfusion appears to be associated with minimal anaesthetic morbidity and mortality in patients with sickle-cell disease.