Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects.

OBJECTIVE: The aim of this study was to characterize the tooth phenotype of CSF-1-deficient op/op mice and determine whether expression of csCSF-1 in these mice has a role in primary tooth matrix formation. DESIGN: Ameloblasts and odontoblasts, isolated from wt/wt frozen sections using laser capture microdissection, were analysed for csCSF-1, sCSF-1 and CSF-1R mRNA by RT-PCR. Mandibles, excised from 8 days op/op and wt/wt littermates, were examined for tooth morphology as well as amelogenin and DMP1 expression using in situ hybridisation. op/opCS transgenic mice, expressing csCSF-1 in teeth and bone using the osteocalcin promoter, were generated. Skeletal X-rays and histomorphometry were performed; teeth were analysed for morphology and matrix proteins. RESULTS: Normal dental cells in vivo express both CSF-1 isoforms and CSF-1R. Compared to wt/wt, op/op teeth prior to eruption showed altered dental cell morphology and dramatic reduction in DMP1 transcripts. op/opCS mice showed marked resolution of osteopetrosis, tooth eruption and teeth that resembled amelogenesis imperfecta-like phenotype. At 3 weeks, op/op teeth showed severe enamel and dentin defects and barely detectable amelogenin and DMP1. In op/opCS mice, DMP1 in odontoblasts increased to near normal and dentin morphology was restored; amelogenin also increased. Enamel integrity improved in op/opCS, although it was thinner than wt enamel. CONCLUSIONS: Results demonstrate that ameloblasts and odontoblasts are a source and potential target of CSF-1 isoforms in vivo. Expression of csCSF-1 within the tooth microenvironment is essential for normal tooth morphogenesis and may provide a mechanism for coordinating the process of tooth eruption with endogenous matrix formation.

[Squamous cell carcinoma on a leg ulcer in the West Indies]. / Carcinome épidermoïde sur ulcère de jambe aux Antilles.

INTRODUCTION: The epidemiology of carcinoma developing on a leg ulcer is poorly, although high incidence rates are reported in Africa. PATIENTS AND METHODS: Retrospective study of cases reported in Guadeloupe, a tropical country with a large population from African descent and with high quality health care level. RESULTS: Sixteen cases, mean age 71, were diagnosed over a 10-Year period in the only referral hospital. The annual incidence was an estimated 0.4/100,000. Preceding ulcers had a long course (mean of 27 Years) and had various causes. Social distress was the rule (14/16 patients). One third of the clearly differentiated (15/16) squamous cell-type tumors exhibited metastatic extension on presentation. At Year 3, the mortality rate was of 40 p. cent. The best survival rate (6 remissions/8 cases) was associated with primary limb amputation. DISCUSSION: Malignant ulcers appeared more frequent in Guadeloupe than in the influent countries of the North, but with an instance 4-fold lower than in Africa. Like many other tropical diseases, socio-behavioral factors may play a major role.

[A principal component analysis of the AGGIR scale in demented elderly patients]. / Analyse en composantes principales de la grille AGGIR chez les patients âgés déments.

AGGIR grid is the national standardized instrument determining aimed at the dependency of old people in France living in institutions as well as in the community. Attribution of the governmental financial assistance APA (Allocation Personnalisée d'Autonomie) depends essentially on the classification of frail old people in 6 degrees of dependency (GIR1 to GIR6). The aim of the present study was to test the reliability of this grid to evaluate the degree of dependency in demented elderly people. Mild, moderate or severe demented patients were included in the study (n= 120). A factorial validation of the A GGIR grid was performed by principal components analysis (PCA). This analysis showed a 5-factor solution: factor 1 named the property factor (27 percent of the variance), factor 2 named the dynamic factor (21 percent),factor 3 named the cognitive factor (20 percent), factor 4 named the external mobility factor (11 percent) and factor 5 named the communication factor (11 percent). The result showed that the AGGIR grid takes physical dependency more into account than psychological and behavioral dependency. This result suggests a need for readjustment of the AGGIR grid for demented patients by adding new variables taking into account psychosocial and behavioral disorders.

Metastatic conventional prostatic adenocarcinoma with diffuse chromogranin A and androgen receptor positivity.

Conventional prostate adenocarcinomas consist mainly of tumour cells of luminal immunophenotype with scattered neuroendocrine (NE) cells. NE cells are defined by chromogranin A (CGA) immunoreactivity. Unlike luminal cells, NE cells lack androgen receptor (AR) and prostate specific antigen (PSA) immunoreactivity. This report describes the first case of conventional prostate adenocarcinoma expressing CGA, PSA, and AR as determined by immunohistochemistry. A 64 year old man was diagnosed with conventional prostate adenocarcinoma in 1993; he underwent cystoprostatectomy in 1994; he developed an iliac bone metastasis in 1997 and mediastinal lymph node metastases in 1999. All specimens obtained during the progression of the disease consisted primarily of luminal cells with only scattered NE cells. In contrast, in samples of non-osseous and osseous metastases obtained at necropsy in 2001, greater than 80% of tumour cells were shown to express PSA, AR, and CGA. This suggests that during tumour progression, conventional prostate adenocarcinomas may evolve into an NE cell phenotype.

Bone histology at autopsy and matched bone scintigraphy findings in patients with hormone refractory prostate cancer: the effect of bisphosphonate therapy on bone scintigraphy results.

Bisphosphonates (BisP) are non-metabolized compounds with high bone affinity used in bone metastasis diagnosis and treatment. Currently, BisP are used to treat hypercalcemia of malignancy as well as to prevent, minimize, or delay skeletal morbidity. These compounds have a long half-life in bone. Thus long-term BisP treatment might saturate bone and interfere with a single-dose scanning agent used for bone scintigraphy when visualizing bone metastases. In an effort to answer this question, this study evaluated the concordance of histology and Technetium99 methylene diophosphonate (Tc99 MDP) bone scintigraphy in the diagnosis of bone metastases in prostate cancer patients. We assessed the concordance of findings between bone scintigraphy and histology using 188 bone biopsies from 11 autopsied patients who died with metastatic prostate cancer, 5 of whom were treated with pamidronate for 2 to 13 months before death. Overall agreement between histology and bone scintigraphy was 84%, 86% in non-pamidronate-treated patients and 82% in pamidronate-treated patients. Scintigraphic bone metastases without histological metastasis (false negatives = 12.7%) were observed in 24 anatomic locations; half of these were in one patient who had been treated with pamidronate and had no histological bone response to the carcinoma. There were only 4 sites where a positive bone scan was not associated with histologic metastasis (false positives = 2.21%). There was no statistical difference between the treated and non-treated group for concordance, specificity, sensitivity, positive and negative predictive values of bone scintigraphy and prevalence of histological abnormality. Long-term pamidronate treatment of prostate cancer bone metastases does not generally affect the ability to detect bone metastases with Tc99 MDP bone scintigraphy.

Factorial validation of the Severe Impairment Battery for patients with Alzheimer's disease. A pilot study.

The Severe Impairment Battery (SIB) estimates the cognitive aptitudes and other skills of severely impaired dementia patients. The main objective of this pilot study was to clearly identify the number of factors present in the SIB and to analyze the relationships between the different cognitive domains explored by the SIB and loss of autonomy. We administered the SIB, the Mini Mental State Examination (MMSE) and two scales of dependency to 48 patients with Alzheimer's disease in its late stages. A factorial analysis (Principal Components Analysis) showed a 4-factor solution for the SIB: a cognitive factor, a praxis and visuospatial functions factor, the reactivity to external stimuli factor and the social aptitudes factor. A factorial analysis involving the dependency scales showed a cognitive factor, a dependency and constructional praxis factor, the reactivity to external stimuli factor and the social aptitudes factor. Reactivity to external stimuli and social aptitudes were not significantly correlated to cognitive aspects nor to dependency. The finding of dependency as a factor different from cognitive deterioration suggests that, in setting a treatment strategy for demented patients, attempts should be made to treat dependency in its own right. In addition, since reactivity to external stimuli and social aptitudes are not related to cognitive aspects nor to dependency, these functions should also be encouraged and stimulated.

The use of parent report to assess the quality of care in primary care visits among children with asthma.

OBJECTIVE: To determine the accuracy of parent report and the accuracy of the medical record in documenting physician performance of elements of pediatric asthma care in the primary care setting. METHODS: A convenience sample of 79 English-speaking parents of 4--12-year old children with asthma presenting to medical center--affiliated inner-city primary care pediatric clinics in the Bronx, Dallas, and Chicago was enrolled, and the office visit was audiotaped. Parents were interviewed 1--16 days after the visit by telephone. OUTCOME MEASURES: Accuracy of parent report was the primary outcome. The "reference standard" was an independent evaluation of the audiotaped record of the primary care visit. The National Asthma Education and Prevention Program was used as a guide to select data elements to assess quality of pediatric asthma care during primary care visits. RESULTS: Sufficient documentation was significantly (P <.001) less likely to be present in the medical record than in the follow-up interview for each element of care. When these elements were combined into a cumulative score, 71% of parent interviews but only 37% of medical records scored > or = 5 (out of a possible 6), with 29% of medical records scoring < 3. Parents were able to accurately report (concordance of parent data with audiotape reference standard) whether or not the visit had included performance of 5 of the 6 elements of care. CONCLUSIONS: Our study suggests that parent telephone interview within 2 weeks after the visit is more accurate than the medical record for documentation of the quality of asthma care in pediatric primary care visits. The medical record was not sufficient to assess the quality of primary care related to asthma, primarily because of missing data. Therefore, our data suggest that assessing quality of care using the medical record will not only bias the findings in the direction of more deficient care but will also make improvement in care more difficult. Further validation of our strategy for using parent report to assess the quality of care in primary care visits will require its application in a variety of other primary care settings.

[Cysticercosis in Guadeloupe]. / Cysticercoses en Guadeloupe.

We report two cases of cysticercosis proved by histology, one in the brain, the other in the orbit. The first case was observed in a traveller, heavy smoker, serologically negative to cysticercosis in whom an isolated cerebral tumoral metastasis was suspected and resected. The lesion was centered by a typical cysticercus of Taenia solium. The second was a periorbital intramuscular nodule observed in a child who had never left our island. The fibroinflammatory nodule was centered by a cysticercus with a scolex without rostellum and without suckers. Its histological aspect led us to the diagnosis of cysticercosis. Three species of Taenia are discussed : T. solium, T. crassiceps and T. bovis. This case shows that the human transmission of the disease may exist in Guadeloupe.

Tissue reaction against a self-setting calcium phosphate cement set in bone or outside the organism.

Calcium phosphate cements are able to set in situ when injected into bone tissue. We evaluated the tissue reaction occurring when a DCPD-based calcium phosphate cement was either set within the bone or implanted when already set. The samples were implanted in rabbit condyles and examined histologically after 8 and 16 weeks. The relative bone surface, the fibrous capsule around the implants and the implant section surface were measured. Solid material seemed to be better tolerated than paste implants. More bone was found at the solid implant contact whatever the implantation time and the solid material degraded much less rapidly. In conclusion, the physico-chemical modification of the biological environment occurring during setting increases the foreign body reaction against the material.

Biomedical applications of maghemite ferrofluid.

The use of cell-targeted ferrofluid in the characterization of modifications of cell membranes is reviewed. Maghemite ferrofluid was synthesized by the Massart method, complexed with dimercaptosuccinic acid (FF). Cell targeting by FF was developed by coupling FF to various biological effectors such as antibodies, lectins, etc, which enabled magnetic cell sorting. Modifications in erythrocyte membranes were studied using FF bound to recombinant human annexin V (AnxFF) which is very sensitive, compared to other Anx-based reagents, in the early detection of phosphatidylserine (PS) exposition on the outer leaflet of the plasma membrane. Thus PS exposition on mouse RBC was detected already after a 24-h storage at 4 degrees C and, transiently, 24 h after their infection by Plasmodium parasites, at which time the parasites are still confined to the liver, thus leading to the recruitment of young RBC and the accumulation of a species, intermediate between reticulocytes and erythrocytes, and the actual RBC target of plasmodial invasion. AnxFF revealed PS exposition on RBC from sickle cell anemia patients, following various inflammations and already after 20 days of human blood storage under blood bank conditions. Such a sensitive detection should be similar to that of macrophages which recognize exposed PS on cells and bring about the latter's elimination from the circulation. AnxFF binding determination was combined with that of cell electrophoretic mobility, glycerol resistance and filterability to characterize RBC membrane modifications in Alzheimer's disease patients which suggested a continuous damage and regeneration in RBC of these patients. A logistic analysis suggested that several three-parameter combinations could permit diagnosis of Alzheimer's disease with up to 95% accuracy. THP1 cells and macrophages, derived themselves by incubation with retinoic acid, were bound to FF and placed in a radio frequency alternating magnetic field. Magnetocytolysis was associated with FF attachment to the cells without damage to non-bound cells and without heating of the surrounding solution.

Increased total 7 alpha-hydroxy-dehydroepiandrosterone in serum of patients with Alzheimer's disease.

Evidence has indicated that circulating adrenal steroid quantitites were significantly changed in patients with Alzheimer's disease (AD). Aside of 3 beta-sulfatation and 3 beta-acylations, levels of dehydroepiandrosterone (DHEA) result from production and metabolic transformation yields. 7 alpha-Hydroxylation of DHEA has been described in humans, and 7 alpha-hydroxy-DHEA may be responsible for the known antiglucocorticoid effects of DHEA. Using a negative ion fragmentometry method with gas chromatography/mass spectrometry on trifluoroacetate derivatives, we measured levels of free 7 alpha-hydroxy-DHEA as well as its sulfated conjugate and its fatty acid esters in serum of 10 female patients with AD and of 8 age-matched healthy control women. Free 7 alpha-hydroxy-DHEA levels in AD and controls were not significantly different (240.2 +/- 37.2 pg/ml and 206.8 +/- 21.6 pg/ml, respectively), but sulfate conjugate levels were significantly increased in AD (p = .01) (262 +/- 28.4 and 145.4 +/- 27.6, respectively) as well as fatty acid esters (p = .041) (65.7 +/- 6.9 and 40.7 +/- 9.2, respectively). These results indicated that the total 7 alpha-hydroxy-DHEA produced was significantly increased in AD (p = .024) and may contribute to the disease-related disturbances of DHEA production and metabolism.

Discrimination of facial identity and of emotions in Alzheimer's disease.

OBJECTIVE: To investigate processing of human faces identity and of emotional expressions in patients with Alzheimer's Disease (AD). BACKGROUND: Mechanisms responsible for discriminating facial identity may be dissociated from those involved in discriminating facial expressions. Patients with prosopagnosia often have preserved capacities for processing emotional facial expressions and occasionally, patients with focal lesions may recognize human faces without being able to recognize their facial expression. Such a dissociation has not been clearly shown in groups of AD patients. METHODS: Thirty-one probable AD patients and 14 control subjects were administered tasks of discrimination of faces and of emotions. RESULTS: AD patients were significantly impaired in discriminating facial identities and in naming and pointing to named emotions, but were comparable to controls in discriminating facial expressions of emotion. The deficits of facial discrimination and of identification of emotions were, on the whole, correlated with the MMS and Raven scores. Discrimination of emotions was not correlated to either test, suggesting that this ability is based on cognitive processes different from those underlying the MMS and the PM47. CONCLUSIONS: This dissociation implies two separate systems, one dedicated to discrimination of facial identities and the other to discrimination of emotions. This is compatible with the modular organization of cognitive deficits in AD and may explain the well known experience that nonverbal communication often remains effective even in patients with severe dementia.

Membrane modifications of red blood cells in Alzheimer's disease.

Red blood cells (RBC) from 24 Alzheimer's disease (AD) patients, 18 age- and sex-matched nondemented (ND) patients, hospitalized in the same facility for orthopedic problems, and 18 healthy volunteers aged 30-52 years were studied in order to gain insight into the nature of RBC membrane modifications in AD. Significant differences were found between RBC from AD and ND patients or young controls respectively for annexin V-binding (45.5 +/- 18.0% vs 27.1 +/- 14.7 and 2.7 +/- 1.9, p = .003), fraction of glycerol resistant cells (30.8 +/- 11.1% vs 19.6 +/- 6.4 and 10.2 +/- 3.1, p = .026), cell electrophoretic mobility in polymer (1.028 +/- 0.022 microns sec-1 V-1 cm vs 1.046 +/- 0.022 and 1.053 +/- 0.021, p = .02) and only limited significance for the filterability (1.46 +/- 0.12 msec vs 1.58 +/- 0.11 and 1.54 +/- 0.11, p = 0.1). A logistic analysis, using simultaneously several features as independent variables, suggested the combined use of annexinV- binding, glycerol resistance, and cell filterability which allowed the assignment of 95% of patients from this cohort to the right group. A prospective analysis of a larger cohort is required for the estimation of the diagnostic value of this test battery. In addition, the high level of annexin binding is characteristic of a disruption of the phospholipid asymmetry in aged or damaged cells, while the high glycerol resistance combined with low electrophoretic mobility an rigidity characterize young RBC, thus indicating an enhanced turnover of RBC in Alzheimer's disease.

[Cutaneo-mucous manifestations of dengue]. / Manifestations cutanéo-muqueuses de la dengue.

OBJECTIVES: To describe muco-cutaneous manifestations of dengue fever, assessing their incidence and histopathological aspects. PATIENTS AND METHODS: During a dengue 2 epidemic, occurring in Guadeloupe in 1994, all patients admitted with a confirmed diagnostic of dengue fever were assessed for dermatological changes by 2 clinicians; 5 patients underwent skin biopsy with immuno-fluorescence staining. RESULTS: Among 39 adult inpatients (Sex ratio 1.1, medium age 41 years) none presented a severe form of the disease, whereas 18/39 (46 p. 100) had some muco-cutaneous changes, associating rash (13 cases (33 p. 100)), mucous membranes involvement (7 cases (18 p. 100)), or minor haemorrhages (6 cases (15 p. 100)). The rash appeared macular, discrete, itching, troncular with peripheral extension, rather than maculo-papular (morbiliform) as usually described. Apart from cases which minor haemorrhagic changes, significatively associated with marked thrombocytopenia (medium 37 x 10(9)/1), dengue cases either with or without muco-cutaneous changes had similar clinical (duration, severity) or biological (neutro-lympho-thrombocytopenia, transaminases) features, and evolution. Histological changes appeared non specific (minor lymphocytic dermal vasculitis, non contributive immuno-fluorescence). DISCUSSION: Clinical and histological features of the rash are unspecific and inconstant: they do not allow an easy and accurate diagnosis. Complete clinical, epidemiological (very recent travel in endemic areas) or biological data should be collected, and early virological or later serological confirmation is needed. As well as travel facilities are growing, the dengue area is extending: dengue fever should therefore be considered in every traveller with fever and rash.

Influence of the structure of three corals on their resorption kinetics.

The aim of this study was to investigate the influence of the structure of corals on their resorption kinetics after implantation in subcutaneous areas. Three types of coral (Porites astreoides, Montastrea annularis and Dichocoenia stokesi) identical in composition but different in structure were implanted for periods of 1 and 2 months in subcutaneous sites in OF1 mice. The resorption of the implants was studied by means of qualitative (histology, scanning electron microscopy, fluorochrome labelling method) and quantitative approaches (gravimetric method). The results of the qualitative study revealed a process of irregular deterioration of the coral, linked to the detachment of crystals at the surface of the implant. The results of the quantitative study showed that the speed of resorption increases with the implantation time and the open porosity of the coral. These reactions are explained by the increase of the surface exchange area in contact with factors responsible for resorption: biological medium and cells. When considering the choice of coral as a bone substitute, these factors must be taken into account to allow the in situ maintenance of the implant over a sufficiently long period of time according to the clinical situation.

The resorption of bone-implanted corals varies with porosity but also with the host reaction.

Three different exoskeletons of coral species Porites asteroides (P), Montastrea annularis (M), and Dichocoenia stokesi (D) were implanted for 2-20 weeks in rabbits. At 2, 4, 8, or 20 weeks, the exoskeletons presented variations in their resorptions depending on the species. To understand the variations in the decreasing speed of the implants despite their similar chemical composition, a study of the surface and architecture of the coral was carried out using scanning electronic microscopy, porosity was evaluated, and growth and differentiation of osteogenic cells cultured in vitro were observed for more than 1 month. At the cellular level, the surface of the implants was identical. Three-dimensional structures of the implants were variable, but the porosity values [P = 42.7%, M = 40.7%, and D = 17.4%] could not completely account for the differences in the resorbing process of the species. Standard histologic studies performed at 2, 4, 8, and 20 weeks after implantation produced the same pattern with P or M, showing aspects of rapid resorption; however, with D there were images resembling those of a foreign-body reaction. It seems that when resorption is not quick enough, a foreign body reaction develops which further slows down the process. This work focuses on the importance of porosity when using coral as bone substitute.