Quality of life and emotional distress in patients and burden in caregivers: a comparison between assisted peritoneal dialysis and self-care peritoneal dialysis.

PURPOSE: Assisted peritoneal dialysis (PD) involving caregivers allows more patients to get started on home-based dialysis with good clinical outcomes, but evidence on patient-reported and caregiver-reported outcomes is lacking. This study aimed to compare assisted PD versus self-care PD on quality of life (QoL) and psychosocial outcomes for patients and caregivers. The effect of PD modality [automated PD (APD); continuous ambulatory PD (CAPD)] in relation to self-care or assisted care was also examined. METHODS: A cross-sectional sample of 231 PD patients [142 self-care (57 APD/85 CAPD) and 89 assisted care PD (45 APD/44 CAPD)], 72 caregivers of assisted PD patients and 39 family members of self-care PD patients completed the Kidney Disease Quality of Life Short Form (KDQOL-SF), World Health Organisation Quality of Life Instrument-brief and the Hospital Anxiety and Depression Scale. Caregivers and family members completed the Lay Care-Giving for Adults Receiving Dialysis questionnaire and Zarit Burden Interview. RESULTS: Case-mix-adjusted comparisons indicated comparable QoL in all dimensions with the exception of physical SF-12 (p = .001) and the KDQOL effects of kidney disease in favour of self-care PD. Levels of anxiety (9.72 ± 4.90; 8.25 ± 5.22) and depression (8.63 ± 3.80; 6.35 ± 4.76) were equivalent in assisted PD and self-care PD, respectively. Assisted PD caregivers reported more task-orientated duties (p = .007), yet levels of perceived burden were equal to those reported by family members of self-care PD. CONCLUSION: Our findings of mostly comparable patient and caregiver outcomes in assisted PD and self-care PD suggest that caregiver burden and QoL should not be a barrier to using assisted PD.

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations.

BACKGROUND: Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. OBJECTIVES: To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations. METHODS: We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5·3 × 10⁻9; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher's exact test; P = 9·0 × 10⁻¹5; OR 5·8), keratosis pilaris (Fisher's exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). CONCLUSIONS: This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.

Sodium monofluoroacetate (Compound 1080) poisoning in dogs.

Sodium monofluoroacetate (Compound 1080) is a widely used pesticide for control of feral animals such as the fox. Accidental poisoning of domestic animals occurs despite strict regulations on 1080 usage. Dogs are particularly susceptible to the toxin. The mechanism of 1080 toxicity, susceptibility of target and non-target species, persistence of 1080 in the environment and risk of accidental poisoning are discussed. Particular emphasis is placed on 1080 toxicity in the dog. Early recognition of intoxication is most important for prognosis and relies upon characteristic clinical signs and diagnostic findings. The treatment of 1080 intoxication remains a challenge with no proven antidotes. However, there are possible benefits from monoacetin, acetamide, calcium salts, colestipol, activated charcoal, peritoneal dialysis, sodium bicarbonate, neurotransmitter modulators and four-methylpyrazole. A recommended treatment protocol for 1080 toxicosis in dogs is included. Safety measures such as the use of wire dog muzzles and investigating alternatives to 1080 in pest control programs may be the key to reducing the incidence of future accidental poisonings.

Uterine artery bleeding and haemoperitoneum during the second trimester in pregnancy.

A case of spontaneous rupture of uterine artery in the second trimester of pregnancy is described. Haemorrhage from rupture of uterine artery during pregnancy was discovered at laparotomy. This was an unusual but serious complication of pregnancy. This condition is extremely rare and one must consider it in cases of incomprehensible abdominal pain with or without haemodynamic collapse. A review of the literature revealed only four similar cases so far. This pregnancy continued till 37 weeks pregnancy and had a spontaneous vaginal delivery. Immediate institution of effective resuscitative measures and early surgical intervention were essential to both foetal and maternal survival.

Viral chemokine receptors and chemokines in human cytomegalovirus trafficking and interaction with the immune system. CMV chemokine receptors.

The ubiquitous, opportunistic pathogen human cytomegalovirus (CMV) encodes several proteins homologous to those of the host organism. Four different CMV genes encode chemokine receptor-like peptides. These genes, UL33, UL78, US27, and US28, are expressed at various stages of infection in vitro. Their functions remain largely unknown. To date, chemokine binding and signalling has only been demonstrated for the US28 gene product. Putative ligands for the other CMV-encoded chemokine receptors are discussed on basis of phylogenetic analysis. The potential roles of these receptors in virus trafficking, persistence, and immune evasion are summarized. Similarly, modulation of expression of the host chemokines IL-8, MCP-1a and RANTES in relation to viral dissemination and persistence is reviewed.

Co-evolution of proteins with their interaction partners.

The divergent evolution of proteins in cellular signaling pathways requires ligands and their receptors to co-evolve, creating new pathways when a new receptor is activated by a new ligand. However, information about the evolution of binding specificity in ligand-receptor systems is difficult to glean from sequences alone. We have used phosphoglycerate kinase (PGK), an enzyme that forms its active site between its two domains, to develop a standard for measuring the co-evolution of interacting proteins. The N-terminal and C-terminal domains of PGK form the active site at their interface and are covalently linked. Therefore, they must have co-evolved to preserve enzyme function. By building two phylogenetic trees from multiple sequence alignments of each of the two domains of PGK, we have calculated a correlation coefficient for the two trees that quantifies the co-evolution of the two domains. The correlation coefficient for the trees of the two domains of PGK is 0. 79, which establishes an upper bound for the co-evolution of a protein domain with its binding partner. The analysis is extended to ligands and their receptors, using the chemokines as a model. We show that the correlation between the chemokine ligand and receptor trees' distances is 0.57. The chemokine family of protein ligands and their G-protein coupled receptors have co-evolved so that each subgroup of chemokine ligands has a matching subgroup of chemokine receptors. The matching subfamilies of ligands and their receptors create a framework within which the ligands of orphan chemokine receptors can be more easily determined. This approach can be applied to a variety of ligand and receptor systems.

Combined radiation and p53 gene therapy of malignant glioma cells.

More than half of malignant gliomas reportedly have alterations in the p53 tumor suppressor gene. Because p53 plays a key role in the cellular response to DNA-damaging agents, we investigated the role of p53 gene therapy before ionizing radiation in cultured human glioma cells containing normal or mutated p53. Three established human glioma cell lines expressing the wild-type (U87 MG, p53wt) or mutant (A172 and U373 MG, p53mut) p53 gene were transduced by recombinant adenoviral vectors bearing human p53 (Adp53) and Escherichia coli beta-galactosidase genes (AdLacZ, control virus) before radiation (0-20 Gy). Changes in p53, p21, and Bax expression were studied by Western immunoblotting, whereas cell cycle alterations and apoptosis were investigated by flow cytometry and nuclear staining. Survival was assessed by clonogenic assays. Within 48 hours of Adp53 exposure, all three cell lines demonstrated p53 expression at a viral multiplicity of infection of 100. p21, which is a p53-inducible downstream effector gene, was overexpressed, and cells were arrested in the G1 phase. Bax expression, which is thought to play a role in p53-induced apoptosis, did not change with either radiation or Adp53. Apoptosis and survival after p53 gene therapy varied. U87 MG (p53wt) cells showed minimal apoptosis after Adp53, irradiation, or combined treatments. U373 MG (p53mut) cells underwent massive apoptosis and died within 48 hours of Adp53 treatment, independent of irradiation. Surprisingly, A172 (p53mut) cells demonstrated minimal apoptosis after Adp53 exposure; however, unlike U373 MG cells, apoptosis increased with radiation dose. Survival of all three cell lines was reduced dramatically after >10 Gy. Although Adp53 transduction significantly reduced the survival of U373 MG cells and inhibited A172 growth, it had no effect on the U87 MG cell line. Transduction with AdLacZ did not affect apoptosis or cell cycle progression and only minimally affected survival in all cell lines. We conclude that responses to p53 gene therapy are variable among gliomas and most likely depend upon both cellular p53 status and as yet ill-defined downstream pathways involving activation of cell cycle regulatory and apoptotic genes.

Selective intraarterial gene delivery into a canine meningioma.

OBJECT: The goal of this study was to evaluate gene delivery to a benign brain tumor. METHODS: A recombinant adenovirus vector bearing the Escherichia coli beta-galactosidase reporter gene was selectively injected into the vascular supply of a spontaneously occurring canine olfactory groove meningioma. The tumor and a small amount of peritumoral brain tissue were removed 5 days after viral injection and stained with X-Gal to assess gene delivery. The authors noted significant beta-galactosidase gene expression by the tumor, but not by surrounding brain tissue. No obvious viral-related cytotoxicity was noted. CONCLUSIONS: The authors found that meningiomas can be successfully transduced by adenovirus vectors by using endovascular techniques.

Glucocorticoid facilitation of cholinergic development in the rat hippocampus.

The role of endogenous glucocorticoids in facilitating the postnatal innervation of septohippocampal cholinergic projections was examined. Septohippocampal cholinergic innervation was determined using two methods. One method involved measuring the optical density of acetylcholinesterase, a marker of cholinergic fibres in the hippocampus. In the other method, acetylcholinesterase-positive fibre counts were made in the hippocampus. Both methods revealed that 14-day-old rats adrenalectomized at 10 days of age have significantly lower densities of acetylcholinesterase in the hippocampal dentate gyrus molecular layer and in the regio inferior when compared to sham-operated control rats. This reduction in hippocampal acetylcholinesterase did not occur when 10-day-old adrenalectomized rats were either injected daily with exogenous corticosterone (0.3 mg/100 g body weight) or when adrenalectomy was conducted at later postnatal ages. In addition, unlike the developing hippocampus, the basolateral nucleus of the amygdala, which is also highly innervated by cholinergic fibres, showed no significant changes in acetylcholinesterase density after adrenalectomy. These observations suggest that glucocorticoids play an important role in supporting the development of cholinergic projections to the hippocampus. Cholinergic innervation of the hippocampus appears especially sensitive to the action of glucocorticoids occurring before the conclusion of the second postnatal week. Furthermore, this glucocorticoid influence is directed rather specifically to the hippocampus in comparison to the basolateral amygdala.

Presynaptic muscarinic cholinergic receptors in the dorsal hippocampus regulate behavioral inhibition of preweanling rats.

The aim of this research was to determine whether early maturation of the dorsal hippocampal cholinergic system mediates behavior exhibited by preweanling rats in the presence or absence of an unfamiliar adult male rat, a threatening stimulus. The behavioral responses that were examined included behavioral inhibition or freezing which emerges at 2 weeks of age and ultrasonic vocalizations. Prior to behavioral testing, oxotremorine, an M2 muscarinic receptor agonist that reduces cholinergic release from presynaptic terminals, was infused into the dorsal hippocampal dentate gyrus. Results demonstrated that 14-day-old rats with bilateral hippocampal infusions of a 1 microgram dose of oxotremorine exhibited significant deficits in freezing when exposed to the adult male rat. Importantly, oxotremorine had no significant effects on ultrasound emission and ambulatory activity when rat pups were tested in social isolation. Thus, effects of oxotremorine in the hippocampal dentate gyrus do not produce global changes in behavior. Results suggest that cholinergic release into the dorsal hippocampus facilitates the display of behavioral inhibition at the end of the second postnatal week. Behavioral deficits in freezing may reflect an oxotremorine-induced disruption of hippocampal cholinergic function underlying the processing of biologically relevant olfactory stimuli as well as mechanisms associated with attention.

Hypoglossia congenita with anterior maxillo-mandibular fusion.

Two cases of hypoglossia congenita with anterior maxillo-mandibular fusion are reported. One is a case of hypoglossia with anterior maxillo-mandibular fusion and the other is a case of hypoglossia-hypodactylia with anterior maxillo-mandibular fusion. This condition presents the anaesthetist with the problem of airway management during the surgery. A simple technique using a nasopharyngeal tube was used for these two cases, with satisfactory results.