[Promoting home support for elderly people with neurocognitive disorders: Caregiver perception of the help-seeking process]. / Favoriser le maintien à domicile des personnes âgées atteintes de troubles neurocognitifs. Perception par les proches aidants de leur processus de recherche d'aide.

BACKGROUND: Caregivers play an essential role in maintaining home care for elderly people with dementia. However, it is difficult for caregivers to target their own needs as well as those of the person with neurocognitive disorders they support on a daily basis. Identifying the needed resources can also be difficult. In order to better assist caregivers in identifying resources needed to support their role, this study aims to understand the factors that influence their help-seeking process. METHODS: This qualitative and descriptive study focuses on the point of view of the main people affected by this problem: caregivers. Eleven caregivers of elderly people with dementia living at home were recruited by convenience sampling. Semi-structured interviews were conducted, and the data were analyzed according to Mast's typology. RESULTS: The factors influencing caregivers help-seeking process were categorized into five themes: 1) service-related (e.g. wait times); 2) personal (e.g. feeling intrusive); 3) experiential (e.g. positive use of a service); 4) relational (e.g. rejection of the elder), and 5) informational (e.g. directed to the right service). CONCLUSION: Caregivers face many challenges in their help-seeking process and want to be more proactively accompanied in a way adapted to their changing needs.

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer.

BACKGROUND: The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer. METHODS: Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed. RESULTS: A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1-2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases. CONCLUSIONS: Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.

Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: is it time to change the gold standard?

OBJECTIVE: To compare the incidence of pelvic lymph node metastases in early stage cervical cancer patients undergoing sentinel lymph node biopsy (SLN) to a matched cohort undergoing pelvic lymphadenectomy. METHODS: All patient data were entered prospectively into an ongoing cervical cancer database. Since April 2004, 87 patients with FIGO stage IA/B1 cervical cancer underwent SLN detection with identification of bilateral SLN. This cohort (cases) was compared to a matched group of patients who underwent complete pelvic lymphadenectomy (controls). The groups were matched 3:1 for tumour size (+/-5 mm), histology, depth of invasion (+/-2 mm), and presence of capillary lymphatic space invasion (CLS). Descriptive statistics were calculated for all variables of interest. The association between cases and controls and lymph node metastases was carried out using a conditional logistic regression analysis. RESULTS: 81 women in the SLN cohort were matched with 1 control, 72 cases with 2 controls, and 65 cases with 3 controls. Among cases, 14 (17%) had pelvic lymph nodes metastases vs. 15 (7%) in the controls (p=0.0059, odds ratio= 2.8, 95% CI=1.3-5.9). Among the 14 cases of SLN metastases, 11 were detected by frozen section and 3 were detected on final paraffin sectioning. All were detected by H and E stains. The size of the SLN metastases ranged from less than 1 mm to 8 mm. CONCLUSIONS: Sentinel lymph node biopsy in early cervical cancer is a more sensitive procedure in detecting pelvic lymph node metastases compared to complete lymphadenectomy.

Intraoperative margin assessment of the radical trachelectomy specimen.

OBJECTIVE: To summarize our experience in the frozen section (FS) assessment of the trachelectomy surgical margin. METHODS: All surgeries from 1994 to 2007 were performed by one surgeon. The FS examination was consistently carried out by a group of gynecologic pathologists according to the protocol described in details in this article. Cases were retrieved from the pathology files and the slides were reviewed by two pathologists. RESULTS: 132 patients were identified with complete pathology records. They ranged from 17 to 46 years old (median 31). Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63 adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78 cases, no residual tumor was seen in the trachelectomy specimens as it was resected by the preceding LEEP or cone. The margin was reported as negative in 123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6 positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2 cases (1.5%); only one of which resulted in a revised margin. No false negative intraoperative assessment was found. CONCLUSIONS: We describe our FS protocol and summarize our data. This protocol is reliable since none of the patients was under-treated.

Structures of oligosaccharides cleaved by base-borohydride from an I, H and Lea active ovarian cyst glycoprotein.

Oligosaccharides were cleaved by base-borohydride from an I, H and Lea active ovarian cyst glycoprotein and purified by Bio-Gel P-6 and paper chromatography. The structures of five oligosaccharides, determined by compositional analyses, quantitative periodate oxidation, chronic acid oxidation, methylation analyses and enzymatic degradations, were as follows: oligosaccharide I, beta DGal1----3DGalNAc-ol; II, beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGalNAc-ol; III, alpha LFuc1----2 beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGalNAc-ol; IV, beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGal1NAcol; and V, beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3 beta DGal1----4 beta DGlcNAc1----6[beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3 beta DGal1----3 beta DGal1----3]DGalNAc-ol. Of the oligosaccharides 60% had a molecular size of a decasaccharide or smaller, the tetra- and pentasaccharides II and III predominating. Oligosaccharides I through IV have been previously isolated from several glycoproteins by other laboratories; the decasaccharide, V, is a new structure.

The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins.

Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies.

Specificity of the monoclonal anti-I antibody (Hy).

In previous work we found that a monoclonal cold hemagglutinin from patient Hy strongly bound antigens contained in stage IV breast cancer sera. To infer the chemical structure of the antigens expressed in the cancer sera, we studied the specificity of the antibody (Hy). The antibody (Hy) had I specificity, based on agglutination scores with adult and cord red blood cells. The binding of the antibody to synthetic and milk oligosaccharides was determined using a solid phase enzyme immunoassay (EIA). The anti-I antibody (Hy) strongly bound LacNAc0-Me, LacNAc1----6Gal, LacNAc1----6 (LacNAc1----3)Gal, LacNAc-1----6 alpha GalNAc, LacNAc1----3LacNAc, and LacNAc, 0.05, 0.06, 0.09, 0.22, 0.35 and 0.75 mM giving 50% inhibition, respectively. The anti-I antibody (Hy), similar to the anti-I antibody (Ma), strongly bound LacNAc1----6Gal, but it differed from the anti-I antibody (Ma) in its cross-reactivity with the i sequence. The anti-I antibody (Hy) showed similar reactivities as the hybridoma monoclonal antibodies M18 and M39 with LacNAc1----6Gal and with the i-active sequence. The EIA procedure is a useful alternative to either radioimmunoassay or immunoprecipitation method in the study of anti-I,i specificities.

Parathyroid adenoma in a young female presenting as recurrent acute pancreatitis with a brown tumour of the mandible-A case study.

INTRODUCTION: Primary hyperparathyroidism is usually seen in females above the age of 50 years, with a prevalence of 21/1000,(1) whereas the incidence in patients aged 12-28 years is less than 5%.(2) A solitary adenoma is responsible for 80% of cases of primary hyperparathyroidism.(3) Primary hyperparathyroidism is most commonly asymptomatic.(4) The incidence of acute pancreatitis associated with hyperparathyroidism is less than 10%.(5,6) The incidence of hyperparathyroidism associated with a Brown tumour is less than 5%.(7) PRESENTATION OF CASE: A 19 year old female patient presented with recurrent acute pancreatitis and swelling over the mandible. Complete investigative workup revealed a solitary parathyroid adenoma causing hyperparathyroidism. Surgical exploration with excision of the parathyroid adenoma was performed, following which the patient recovered uneventfully. DISCUSSION: The patient was initially managed as a case of acute pancreatitis, and although not suspected initially, a high index of suspicion for hyperparathyroidism developed after a biopsy of the mandibular swelling showed the presence of osteoclastic giant cells indicating the possibility of a Brown tumour. Further investigations then revealed the presence of a solitary parathyroid adenoma with coexistent hyperparathyroidism which was then managed surgically. CONCLUSION: The young age of the patient, and her presentation with acute pancreatitis and a Brown tumour of the mandible make this an extremely rare presentation of parathyroid adenoma.

Hemolytic anemia caused by auto anti-N.

The second case of hemolytic anemia caused by auto anti-N, occurring in a 7-year-old boy, is described. The antibody was IgG, as shown by the use of specific anti-human IgG Coombs sera, failure of inactivation by 2-mercaptoethanol, and chromatographic separation on a G-200 Sephadex column.

Interobserver agreement for endometrial cancer characteristics evaluated on biopsy material.

A shift toward a disease-based therapy designed according to patterns of failure and likelihood of nodal involvement predicted by pathologic determinants has recently led to considering a selective approach to lymphadenectomy for endometrial cancer. Therefore, it became critical to examine reproducibility of diagnosing the key determinants of risk, on preoperative endometrial tissue samples as well as the concordance between preoperative and postresection specimens. Six gynaecologic pathologists assessed 105 consecutive endometrial biopsies originally reported as positive for endometrial cancer for cell type (endometrioid versus nonendometrioid), tumor grade (FIGO 3-tiered and 2-tiered), nuclear grade, and risk category (low risk defined as endometrioid histology, grade 1 + 2 and nuclear grade <3). Interrater agreement levels were substantial for identification of nonendometrioid histology (κ = 0.63; SE = 0.025), high tumor grade (κ = 0.64; SE = 0.025), and risk category (κ = 0.66; SE = 0.025). The overall agreement was fair for nuclear grade (κ = 0.21; SE = 0.025). There is agreement amongst pathologists in identifying high-risk pathologic determinants on endometrial cancer biopsies, and these highly correlate with postresection specimens. This is ascertainment prerequisite adaptation of the paradigm shift in surgical staging of patients with endometrial cancer.

Androgenetic complete mole with trisomy 13: report of a case with microsatellite genotyping and review of the literature.

Hydatidiform moles are gestational diseases with abnormal development of the villous trophoblast and characterized by an excess of paternal to maternal genetic material. Complete moles are usually diploid and androgenetic, and are thought to develop after the fertilization of an "empty ovum" by either a haploid spermatozoon or two spermatozoa. We report a case of a complete mole in which fluorescence in situ hybridization (FISH) incidentally disclosed trisomy 13. Microsatellite genotyping showed a single allele at each of the markers tested on the chorionic villi, and comparison with parental peripheral blood specimens revealed that the markers were all of paternal origin. These results confirmed the paternal origin of all three copies of chromosome 13, and the isodisomy for each chromosome was consistent with duplication of a monospermic fertilization event and subsequent non-disjunction. To the best of our knowledge, this is the only case of an androgenetic complete mole with trisomy 13 described in the scientific literature. We present a review of the literature and hypothesize that the trisomy 13 in our case likely resulted from non-disjunction of chromosome 13.

Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi.

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 µg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 µg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 µg/ml. Flavone immobilized female adult worms at 31.2 µg/ml (MTT>80%) and microfilariae at 62.5 µg/ml. Rutin killed microfilariae at 125 µg/ml and inhibited MTT-reduction in female worms for >65% at 500 µg/ml. Naringin had adulticidal effects at 125 µg/ml while chrysin killed microfilariae at 250 µg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.

The structural relationship of blood group-related oligosaccharides in human carcinoma to biological function: a perspective.

Blood group-related oligosaccharides have been isolated from a limited number of carcinomas. The carcinoma-associated oligosaccharides show chain elongation, for example due to repeating Gal 1,4 GlcNAc 1,3 sequences, or a higher degree of branching, which permit increased sialylation and fucosylation. Abnormal carbohydrate structures have been demonstrated on tumor cell membranes by immunological techniques, which suggests deletion of ABH, accumulation of 'crypt' antigens such as I and T antigens, and abnormal expression of Lewis antigens. Changes in carcinoma-associated oligosaccharides can result from altered biosynthetic processing in the Golgi apparatus or the occurrence of abnormal tumor glycosyltransferase isoenzymes. Structural alterations of oligosaccharides on the tumor cell membrane are related to the regulation of tumor growth, cell-cell interaction, cell differentiation, and metastasis. Glycoproteins secreted by tumor cells into the circulation evoke cellular and humoral immunity and cause immune suppression by binding to cytotoxic T lymphocytes and lymphocyte subsets. The relationship of oligosaccharide structures to biologic function awaits elucidation.

Subclinical hemolytic disease of the newborn associated with IgG anti-Lub.

An anti-Lub antibody with a titer of 128 to 256 was found in a pregnant woman. The antibody was IgG of the IgG1 subclass. Two newborns of successive pregnancies were free of clinical hemolytic disease of the newborn. The failure of this antibody to cause clinical hemolytic disease is ascribed to the weak expression of the Lub antigen on cord red blood cells.

Red blood cell cold agglutinins and B lymphocyte cytotoxins in breast cancer sera.

Cytotoxic activity towards B-lymphocytes in sera from individuals with breast carcinoma was related to red blood cell cold agglutinin levels and IgM values. The control group consisted of 32 females with a similar age distribution. Significant increases in red blood cell cold agglutinin levels were found in the group of cancer patients and the group with the histological category of mucin-producing carcinoma with lymphocyte cytotoxins (p less than 0.025, respectively), in comparison to the control group and cancer patients without lymphocyte cytotoxins. Serum IgM concentrations were significantly increased in the group of cancer patients (p less than 0.025) and the group with mucin-producing carcinoma (p less than 0.01) with lymphocyte cytotoxins, in comparison to cancer patients and controls without lymphocyte cytotoxins. The lymphocyte cytotoxins were completely or partially adsorbed by red blood cells in 58% of the positive sera. These results suggest that red blood cell cold agglutinins constitute a portion of cytotoxic anti-B lymphocyte antibodies. At present it is unknown whether the lymphocytotoxic antibodies in breast cancer patients are of importance in immunologic host defenses.

Human embryonic liver cell differentiation. I. Changes in specific mRNA synthesis correlates with parameters signaling oncologic alterations.

When incubated in preconditioned medium, i.e. spent media from the hepatocellular carcinoma (PLC/PRF/5) cell cultures, human embryonic liver (HEL) cells differentiate and acquire oncologic phenotypes. This is caused by transcriptional alterations in fetal gene expression. This occurs when hepatocytes are proliferating rapidly and secreting alpha fetoprotein (AFP), and later when the quiescent state is reached with secretion of albumin (ALB). The present studies examined the parameters signaling oncologic transformation during liver cell differentiation in the conditioned medium. mRNAs coding for AFP, ALB and HBsAg were isolated from HEL, adult liver cells (ADLC) and from PLC/PRF/5 cells, respectively. cDNA molecules complementary to these polysomal mRNA molecules were constructed and labeled with 32P. These tracers were used to quantitate changes in cellular mRNA X AFP, mRNA X ALB and mRNA X HBsAg directly by DNA molecular hybridization during HEL cells cultivation in the preconditioned medium. Under these conditions, the changes in cellular mRNA X HBsAg and mRNA X AFP correlated with an increased tumorigenicity in athymic Nu/Nu mice, membrane galactosyltransferase and phospho-tyrosine kinase activities.

Variation of cold agglutinin levels.

Cold agglutinin levels were determined in 120 individuals ranging in age from 1 to 64 years using untreated and ficin-treated group O erythrocytes. The geometric mean titer for untreated cells was 5.7 +/- 1.1 SEM and for ficin-treated cells 18.7 +/- 1.1 SEM. The mean titers and scores for various blood groups were not significantly different. Titers and scores correlated significantly to total serum IgM concentration (p less than 0.001). Females had significantly higher cold agglutinin levels than males (p less than 0.001). A significant decrease of cold agglutinins occurred in the 26- to 64-year age group as compared to the 11- to 25-year age group (p less than 0.01). The data should contribute to a clearer understanding of the biological impact of cold agglutinins.