A Place to Live and to Die: A Qualitative Exploration of the Social Practices and Rituals of Death in Residential Aged Care.

In many countries, an increasing proportion of deaths occur in residential aged care (RAC) (nursing homes) meaning that these have become both a place to live - a home- and a place to die. This paper reports on death practices and rituals in 49 RAC facilities in Aotearoa/New Zealand narrated in semi-structured interviews with staff. Themes coalesced around 'good death'. Dying alone was not seen as a good death and the demands of trying to prevent this caused tension for staff. Meeting family wishes, post death decision-making, after death practices and rituals, including communicating and remembrance of the death, were explored as part of good death. Overall, death rituals in RAC were limited. Balancing the needs of the living, the dying and the dead created tension. The rituals and practices facilities are currently enacting in death/post-death require attention, since more people will die in RAC with increasingly diverse needs.

Parental origin and mechanisms of formation of triploidy: a study of 25 cases.

Triploidy is one of the most frequently observed chromosome abnormalities in spontaneous abortions in humans. The parental origin of the additional chromosome set is known to have a major impact on the phenotype of the foetuses and to result in differences in size and structure of the placenta. Early studies based on cytogenetic polymorphisms indicated a preponderant diandric origin of the triploidies; such detection method, however, is known to be prone to error. Other studies revealed a predominant digynic origin in cases with longer intrauterine survival. It is now thought that, to some extent, a detection bias in favour of cases with associated partial hydatidiform moles may account for the high incidences of diandric cases reported in some studies. Furthermore, depending on the gestational age of the cases analysed there may indeed be differences in the proportion of diandric and digynic triploidies. We investigated the parental origin and mechanisms of formation of triploidy in a group of 25 probands with gestational ages ranging from 8 to 37 weeks. DNA samples were extracted from foetal material and from blood samples of the parents, and were analysed using microsatellite markers. The parental origin of the triploidies was found to be maternal in 20 cases and paternal in 5. Regarding the digynic cases, an error at meiosis I was inferred in 10 cases, whereas in the other half an error occurred at meiosis II. All five diandric cases included in this study were found to be due to dispermy. No significant differences in the average maternal ages were found amongst the different subgroups of patients.

Isochromosomes 12p and 9p: parental origin and possible mechanisms of formation.

In a recent study Bugge et al and Kotzot et al reported that isochromosomes 18p originate mainly from maternal meiosis II nondisjunction, followed by misdivision. In order to determine if there is a common mechanism for isochromosome formation, three cases with mosaicism for an additional isochromosome 12p and three cases with tetrasomy 9p were studied. Two probands with isochromosomes 12p and the three cases with isochromosome 9p showed 3 alleles (two different maternal alleles and one paternal allele) at several loci mapping to distal 12p and 9p, respectively. Maternal heterozygosity for distal markers was reduced to homozygosity for markers closer to the centromere in both i(12p) cases and in one i(9p) case. For one patient with isochromosome 12p, the maternal band was clearly stronger than the paternal one at some loci, but two distinct maternal alleles were never seen. For one foetus and the patient with tetrasomy 9p, distal markers showed maternal heterozygosity. All proximal markers were not informative in these two i(9p) cases. Our findings indicate common features in different autosomal isochromosomes: the origin of the isochromosomes analysed in predominantly maternal; and a common mechanism appears to underlie their formation, namely due to meiosis II nondisjunction followed by a rearrangements leading to duplication of the short and loss of the long arm.

Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes.

We report on a family with a balanced complex chromosomal rearrangement (CCR) involving eight breakpoints between chromosomes 6, 7, 18, and 21 in the father. All three sons inherited one derivative chromosome from the father and in addition each inherited a different recombinant chromosome resulting in a partial trisomy 6q in the first, an apparently balanced karyotype in the second, and a partial trisomy 7q in the third son. Fluorescence in situ hybridisation (FISH) and microsatellite analysis were essential for the identification of the breakpoints. In addition, the results were confirmed by a 24-colour FISH experiment using the spectral karyotyping (SKYtrade mark) system. Paternal origin of the de novo CCR in the father was demonstrated for the first time by haplotype analysis. This is the second report of a CCR leading to simpler but unbalanced translocations in offspring as a consequence of recombination during gametogenesis, and the first report of a family case of CCR exhibiting as many as eight breakpoints in the transmitting carrier. The initial prediction that viable offspring would be quite unlikely had to be revised after the birth of three children. Genetic counselling of carriers of balanced complex rearrangements has to consider a higher probability for unbalanced recombinations than has been so far commonly assumed.

Terminal deletion, del(1)(p36.3), detected through screening for terminal deletions in patients with unclassified malformation syndromes.

We report on a 4 year-old girl with a 1p36.3-pter deletion. Clinical findings included minor anomalies of face and distal limbs, patent ductus arteriosus, the Ebstein heart anomaly, and brain atrophy with seizures. Conventional GTG-banded chromosome analysis revealed a normal (46,XX) result. Subsequent analysis by fluorescent in situ hybridization (FISH) using distal probes demonstrated a deletion of 1p36.6-pter. Molecular investigations with microsatellite markers showed hemizygosity at three loci at 1p36.3 with loss of the paternal allele. The deletion of 1p36.3 is difficult to identify by banding alone; indeed, our patient represents the third reported case with a del(1)(p36.3) that was detected only after more detailed analysis. In all three cases the deletion was detected through screening of patients with multiple congenital anomalies/mental retardation syndromes suggestive of autosomal chromosome aberrations for subtelomeric submicroscopic deletions by means of FISH or microsatellite marker analysis. On the basis of these observations we highly recommend that FISH with a subtelomeric 1p probe be routinely performed in patients with similar facial phenotype, severe mental retardation and seizures, and a heart malformation, particularly the Ebstein anomaly.

Molecular and clinical correlation study of Williams-Beuren syndrome: No evidence of molecular factors in the deletion region or imprinting affecting clinical outcome.

Williams-Beuren syndrome (WBS) results from a deletion of 7q11.23 in 90-95% of all clinically typical cases. Clinical manifestation can be variable and therefore, deletion size, inherited elastin (ELN) and LIM kinase 1 (LIMK1) alleles, gender, and parental origin of deletion have been investigated for associations with clinical outcome. In an analysis of 85 confirmed deletion cases, no statistically significant associations were found after Bonferroni's correction for multiple pairwise comparisons. Furthermore, the present data do not support presence of imprinted genes in the WBS common deletion despite a nonsignificant excess of maternal over paternal deletions. Maternal deletion cases were more likely to have a large head circumference in the present data. Also, pairwise comparisons between individual WBS clinical features have been conducted and revealed significant associations between (1) low birth weight and poor postnatal weight gain (<10th percentile at the time of examination) and (2) transient infantile hypercalcemia and a stellate iris pattern. The latter association could indicate a common underlying etiology.

In vivo properties of the urinary bladder wall and their modulation by estradiol and raloxifene in a rat model.

OBJECTIVES: Urinary incontinence is a common symptom of urogenital aging that affects a considerable proportion of postmenopausal women. Morphological and morphometrical modulation of the bladder by estrogen are known. Yet data showing that this translates into changes of in vivo function of the urinary bladder are missing. METHODS: We measured urodynamic parameters in anaesthetized, surviving rats. Following ovariectomy animals were divided into three groups and fed either an estradiol-, raloxifene-, or unsupplemented soy-free formula for ten weeks. Via a transurethral catheter the intravesical pressure was recorded during a stretch period (the urinary bladder was filled), and a one-minute isometric accommodation period immediately after the filling period. Upon termination of the experiment upper and lower halves of the bladder were processed histologically. RESULTS: The estrogen-, and raloxifene-treated animals showed significantly higher pressures in responses to rapid stretch. Bladder compliance during the isometric period on the other hand was not significantly affected by these treatments. Thickness of the epithelial layer, collagen content and muscle bundles were significantly increased by estrogen and raloxifene treatment. CONCLUSIONS: This is a good animal model to investigate modulation of detrusor muscle contractility and stiffness. Both estradiol and raloxifene increase bladder contractility. Urinary bladder morphology indicates that estrogen acts primarily in the upper half of this organ since significant effects on collagen content and muscle fibers are only found in this part.

Adolescent knowledge, values, and coping strategies: implications for health in sub-Saharan Africa.

PURPOSE: The purposes of this study were to investigate the experiences and knowledge of adolescents living in an urban center in Kenya and to understand how the decisions they make affect their physical and psychological health. METHODS: A sample of 216 adolescents was drawn and they met weekly in small groups with trained facilitators for a period of 6 months. A research team monitored the developments of the groups and the topics they discussed. The findings were corroborated by the adolescents. RESULTS: It was found that adolescents were primarily concerned with developing a coherent and consistent set of personal values which would govern their behavior. Unfortunately, they could not always achieve those values and they resorted to dysfunctional coping strategies which were injurious to their health. CONCLUSIONS: The role of the adolescent in developing countries is complex and poorly defined. In a period of unprecedented change, an urgent and comprehensive review is necessary by all sections of society if the health of this group is to improve.

PIP: This study investigated the experiences and knowledge of adolescents in Nairobi, Kenya to understand how the decisions they make affect their health. Data were gathered from a sample of 216 youths aged 12-22 years (equally divided between males and females) who lived in lower socioeconomic areas. The youth met in groups of 12 over a period of 6 months. An equal number of groups were all male, all female, and mixed. The educational distribution of the participants varied according to age and was normal for Nairobi. Each group met with a qualified counselor who facilitated discussion. The minutes of the group meetings provided qualitative data. During the first 6 weeks of meetings, the facilitators led the groups through a series of exercises to create an atmosphere in which the youth felt free to express themselves. During the 20-week second stage, an open agenda was used, and the facilitators restricted their role to clarifying issues and resolving conflicts. The topics, which were ranked according to the percentage of time they consumed, included (in order) emerging sexuality, drugs, alcohol, pregnancy, rape (many of the girls were victims and some of the boys were perpetuators), suicide, marriage, religion, abortion, sexually transmitted diseases/AIDS, parents, contraceptives, money, masturbation, lying, politics, language, and leisure/sports. Values expressed in order of importance were parental love, education, honesty, employment, religion, money, personal freedom, friendship, beauty, marriage, and politics. Coping strategies were use of drugs, stealing, masturbation, alcohol, providing sex for favors, noncooperation, lying, secret language, clubs, silence, religion, and exercise/sports. It is concluded that social changes in developing countries have exacerbated the ambiguity experienced by adolescents and that a comprehensive review of adolescents is necessary in order to improve their health.

Management of the gastrointestinal tract and nutrition in patients with cloacal exstrophy.

Cloacal exstrophy is a rare condition in which there is a complex set of congenital anomalies that affect multiple-organ systems, including the gastrointestinal tract. Twenty-six patients with cloacal exstrophy have been treated at the authors' institution during the last 20 years. Gastrointestinal features usually included omphalocele, exstrophy of an everted cecal plate, a short blind-ending distal colon, imperforate anus, and, occasionally, a shortened small bowel. Additional gastrointestinal anomalies included four cases of colonic duplication, one duodenal web, and one malrotation. The average time until the initiation of enteral feeding after initial surgery was 15.6 days, and the time until discontinuation of total parenteral nutrition (TPN) was 36 days. One patient with short bowel syndrome died of TPN-associated liver failure. Five other patients exhibited short bowel physiology, but ultimately each was weaned from supplemental intravenous hyperalimentation. Four patients have undergone posterior sagittal anorectoplasty, and one has had perineal anoplasty. Of these patients, two are continent and one is free of soilage on a bowel management program. In the authors' experience with management of the gastrointestinal tract and nutrition in patients born with cloacal exstrophy, many patients initially exhibited short bowel physiology, although most eventually adapted. However, very few patients have been able to achieve bowel control.

Towards a unified theory for HIV / AIDS counselling.

PIP: This article explores the introduction of a unified theory for HIV/AIDS counseling. Counseling intervention adopted by the WHO Global Program on AIDS was guided and informed by the behavioral theory of counseling. This approach was aimed at preventing the spread of infection and providing psychosocial support to those who are already sick. It is argued that counseling based on behavioral theory provides a limited therapeutic intervention and fails to meet all the needs that are associated with HIV/AIDS issues. Thus, other theoretical sources were explored which resulted to a unified theory of counseling that drew upon three main sources including behavioral, psychoanalytic, and humanistic theories. It is argued that future counseling interventions should be redirected from a disease-centered approach to a person-centered approach. Introduction of the unified theory can be facilitated by the use of the self-concept model. In conclusion, the unified theory provides the therapeutic foundation upon which a comprehensive counseling intervention can be based.^ieng

AIDS / HIV counseling in the developing world.

PIP: The second decade of the AIDS pandemic makes increasingly apparent the political, legal, cultural, ethnic, and economic aspects of AIDS. The dichotomy between developments of the pandemic in the developed and the developing world is apparent in HIV counseling and testing. The practice of HIV counseling in the developed world relies upon the WHO/GPA model of pre- and post-test counseling. This model responds to the personal risk of being HIV tested by requiring informed consent during pre-test counseling. However, informed consent similarly applied in the developing world has not been so effective. In the developed world, a pharmacological response to the virus is possible, offering an incentive to be tested and subsequently treated. In the developing world, no such drug treatment exists, there is less imperative to discover one's HIV status, and relatively few return for their test results or benefit from education during post-test counseling. The tendency to delay counseling and testing until symptoms appear results in confirmed fears by pre-test counseling alone. The Network of AIDS Researchers in Eastern and Southern African (NARESA) has devised a new counseling model, using an eclectic and integrated approach. The first cohort of 12 counselor-trainers was trained over a 1-month period at NARESA's Center in Nairobi. Participants explored their own subjective experiences through an interactive model. Counseling skills were explored and practiced in small groups. Interactions were videotaped so that participants could analyze their behavior. These counselor-trainers have returned to their countries to organize counseling courses based upon this model and a cross-cultural counseling manual. Counseling is one of the few therapeutic interventions which is affordable and feasible for developing countries. The NARESA initiative will establish a network of counselors who will evaluate this eclectic model for the developing world.^ieng

Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria.

The Angelman syndrome (AS) is caused by genetic abnormalities affecting the maternal copy of chromosome region 15q12. Until recently, the molecular diagnosis of AS relied on the detection of either a deletion at 15q11-13, a paternal uniparental disomy (UPD) for chromosome 15 or imprinting mutations. A fourth class of genetic defects underlying AS was recently described and consists of mutations of the UBE3A gene. The vast majority of mutations reported so far are predicted to cause major disruptions at the protein level. It is unclear whether mutations with less drastic consequences for the gene product could lead to milder forms of AS. We report on our results obtained by screening 101 clinically diagnosed AS patients for mutations in the UBE3A gene. Non-stringent clinical criteria were purposely applied for inclusion of AS patients in this study. The mutation search was carried out by single-strand conformation polymorphism (SSCP), and SSCP/restriction fragment length polymorphism (RFLP) analyses and revealed five novel UBE3A gene mutations as well as three different polymorphisms. All five mutations were detected in patients with typical features of AS and are predicted to cause frameshifts in four cases and the substitution of a highly conserved residue in the fifth. The results we obtained add to the as yet limited number of reports concerning UBE3A gene mutations. Important aspects that emerge from the data available to date is that the four classes of genetic defects known to underlie AS do not appear to cover all cases. The genetic defect underlying approximately 10% of AS cases, including some familial cases, remains unknown.

Clonal maintenance of imprinted expression of SNRPN and IPW in normal lymphocytes: correlation with allele-specific methylation of SNRPN intron 1 but not intron 7.

DNA methylation is a heritable and reversible modification to CpG sites in the mammalian genome. Parental allele-specific methylation is hypothesized to be important in the establishment and maintenance of imprinted gene expression; however, dynamic changes in allele-specific patterns have been observed. The upstream regulatory region of the small nuclear riboprotein N gene (SNRPN) is an important imprinting control region (ICR) for establishing and maintaining the methylation imprint in the locus on 15q11-13 associated with Prader-Willi and Angelman syndromes (PWS). To compare directly the role of allele-specific methylation patterns and the maintenance of imprinted expression in the PWS region, clonal populations of normal T lymphocytes were cultured for 22-25 generations. A novel long-range semi-nested polymerase chain reaction (PCR) strategy was utilized in order to span two different methylation sites, and a polymorphism within SNRPN was used so that allele-specific methylation of both sites could be determined. Reverse transcription/PCR followed by polymorphism analysis was also performed in order to determine parental allele-specific transcription. Exclusive paternal expression at both SNRPN and IPW was maintained in all T cell clones and correlated with maternal methylation of the intron 1 NotI site. In contrast, biallelic methylation was observed in all clones at the previously described paternally methylated HpaII site in intron 7. These results demonstrate that the maintenance of paternal expression of SNRPN and IPW correlates with a strict clonal maintenance of allele-specific methylation at the CpG-dense 5' end of SNRPN. Differential maintenance of methylation sites within imprinted genes may depend on the density and chromatin organization of surrounding CpG sites.

The negotiating strategies determining coitus in stable heterosexual relationships.

Heterosexual behaviour is a complex subject and one which is aggravated by confounding variables. Few studies have investigated the way in which one variable, namely coitus, is initiated and negotiated in stable marital relationships. As the HIV/AIDS pandemic spreads in sub-Saharan Africa, the subject of marital coitus becomes of increasing concern. This study tests a methodology of semi-structured interviews and diary-keeping techniques to investigate how the activity is initiated and negotiated. A research team monitored the study and evaluated the research techniques. The study concluded that the HIV/AIDS pandemic is affecting the initiation and negotiation of coitus between marital partners and that the partners wish to renegotiate the relationship, but the mechanisms for renegotiation are not at present available.

PIP: Qualitative research involving married couples in Kenya indicated that the acquired immunodeficiency syndrome (AIDS) pandemic in sub-Saharan Africa is having a profound effect on coitus; however, couples lack the interpersonal skills to negotiate safe sex. Study participants included 10 men and 10 women recruited from family planning, health, and social service centers in Nairobi; all were involved in stable marital relationships of at least one year's duration (average, 6.5 years). During the three-month study period, subjects participated in weekly semi-structured interviews and kept a diary of all sexual activities. Coitus occurred an average of three times a week and its timing was under the control of the husband. Condom use was rejected due to its association with infidelity. Men became increasingly willing to acknowledge extramarital sex as the study progressed and they became comfortable with the research team; many of them were concerned about the risk of AIDS associated with this behavior. The diaries indicated that the sexual negotiation process begins with recognition of a conscious need and proceeds to initiation strategies (e.g., a romantic glance, touching of partner, a gift), which is either accepted or rejected. At times, men bypass the negotiation stage and violently force their wives to have sex. Most initiating and negotiating strategies were nonverbal and acquired unconsciously, impeding open discussion of physical and emotional needs. The qualitative methodologies employed in this study served to provide participants with a vocabulary for discussing sexual matters and motivation to re-negotiate a monogamous sexual relationship.

Severe intra-uterine growth retardation in a patient with maternal uniparental disomy 22 and a 22-trisomic placenta.

We report on a maternal uniparental disomy of chromosome 22 in a patient with severe intra-uterine growth retardation. Karyotyping of a placental tissue revealed non-mosaic trisomy 22, whereas lymphocyte chromosomes from the newborn were normal 46,XY. Microsatellite analysis using DNA extracted from white blood cells showed maternal uniparental heterodisomy for chromosome 22. Thus, the conceptus started as maternal trisomy due to meiotic non-disjunction, and trisomy rescue occurred subsequently through loss of the paternal homologue resulting in maternal uniparental disomy. Normal phenotypes in previous reports have suggested that maternal UPD 22 has no impact on the phenotype. Thus, growth retardation in this patient was probably caused by dysfunction of the trisomic placenta.

A supernumerary marker chromosome originating from two different regions of chromosome 18.

By random amplification of a microdissected chromosome using the degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) and forward painting (microFISH), we characterised an extra structurally abnormal chromosome (ESAC) or supernumerary marker chromosome in a mentally retarded girl with a pattern of dysmorphic features. It could be clearly shown that the small marker chromosome originates from two different regions of chromosome 18, 18p11.1-->18q11.1 and 18q12.3-->18q21.1 respectively. Maternal origin of the de novo ESAC and biparental origin of the normal homologues of chromosome 18 were shown by PCR of several highly polymorphic microsatellites. In this case, application of microFISH was a prerequisite for rapid and precise characterisation of an ESAC. A definite identification of this discontinuous supernumerary marker chromosome would not have been possible using FISH with centromere specific probes or multicolour FISH approaches.

Duplication of segment 1p21 following paternal insertional translocation, ins(6;1)(q25;p13.3p22.1).

A moderately mentally retarded 3 year old boy showed minor anomalies including a prominent forehead and flat occiput, exophthalmos, large and prominent ears, high arched palate, umbilical hernia, sacral dimple, and irregular position of the toes. Cardiac sonography disclosed a chorda running through the left ventricle. Cytogenetic investigation of the family showed a balanced insertional translocation of segment 1p13-->p22 into distal 6q in the father which had led, through unbalanced segregation, to duplication of 1p13.3-->p22.1 in the proband. Familial duplication of such a small interstitial segment of 1p has not been reported previously, and the paucity of abnormal physical findings in the proband compared to previous patients with a similar aberration is remarkable.

Quantitative localization of heterogeneous methyl-CpG-binding protein 2 (MeCP2) expression phenotypes in normal and Rett syndrome brain by laser scanning cytometry.

Rett syndrome (RTT) is an X-linked, dominant neurodevelopmental disorder caused by mutations in MECP2, encoding the methyl-CpG-binding protein 2 (MeCP2). A major paradox in the pathogenesis of RTT is how mutations in ubiquitously transcribed MECP2 result in a phenotype specific to the central nervous system (CNS) during postnatal development. To address this question, we have used a novel approach for quantitating the level and distribution of wild-type and mutant MeCP2 in situ by immunofluorescence and laser scanning cytometry. Surprisingly, cellular heterogeneity in MeCP2 expression level was observed in normal brain with a subpopulation of cells exhibiting high expression (MeCP2(hi)) and the remainder exhibiting low expression (MeCP2(lo)). MeCP2 expression was significantly higher in CNS compared with non-CNS tissues of human and mouse by automated quantitation of MeCP2 on multiple tissue arrays. Quantitative localization of MeCP2 expression phenotypes in normal human brain showed a mosaic, but distinct, distribution pattern, with MeCP2(hi) neurons highest in layer IV of the cerebrum and MeCP2(lo )neurons highest in the granular layer of the cerebellum. In female RTT brains, MECP2 mutant-expressing cells were identified as cells negative for the MeCP2 C-terminal epitope. MECP2 mutant-expressing cells were randomly localized in Rett cerebrum and cerebellum and showed normal MeCP2 expression with N-terminal-specific anti-MeCP2. These results demonstrate a CNS-specific cellular phenotype of MeCP2 high expression and suggest that MECP2 mutations in RTT are only manifested in MeCP2(hi) cells. In addition, our results demonstrate the power of laser scanning cytometry in examining complex cellular phenotypes in disease pathogenesis.