Expression of glycine receptors in rat sensory neurons vs. HEK293 cells yields different functional properties

In neurodegenerative diseases, such as Alzheimer's disease or HIV encephalitis, neuronal DNA fragmentation has been observed at unexpected high frequencies, without definitive evidence for activation of an irreversible apoptotic pathway. The wobbler mouse is a suggested genetic model of neurodegenerative disease. The mutant mouse develops normally until the fourth week of age when atrophy and weakness of forelimb muscles become apparent. There is a slow progression of the disease and wobbler mice may survive for several months. Spinal cord examination reveals the presence of several motoneurons with perikaryal vacuolar degeneration. In this study, we observed, using terminal dUTP nick-end-labelling staining in mutant spinal cord sections, a massive although very transient DNA fragmentation in different cell types, including glial cells and motoneurons, before the apparition of any clinical symptoms. In older wobbler mice, this DNA fragmentation had completely disappeared and the majority of motoneurons survived. To our knowledge, this is the first example of a massive and transient DNA fragmentation in the central nervous system during the early course of a neurodegenerative disease.     

Elevated expression of ETS-1 gene in a metastatic, tumorigenic human prostate epithelial cell line transformed by the v-Ki-ras oncogene

We investigated the inhibitory effects of intrasplenic combination therapy with OK-432 and recombinant interleukin-2 (IL-2) on liver metastasis of colorectal carcinoma. Intrasplenic administration group significantly inhibited the development of liver metastasis compared with subcutaneous administration group (p<0.05). Combination therapy significantly inhibited the development of subclinical liver metastasis compared with that in the control group. Combination therapy decreased the percentage of cells expressing CD8a, which may be a part of effective factors of combination therapy, and improved overall survival rate. These findings suggested intrasplenic combination therapy with OK-432 and IL-2 might be effective in inhibiting liver metastasis of colorectal carcinoma.     

Factors associated with analgesic and psychotropic medications use by community-dwelling older people with chronic pain

OBJECTIVE: The present study sought to examine use prevalence and factors associated with use of analgesic and psychotropic medications in community-dwelling older people with chronic non-malignant pain. METHOD: The study group comprised 193 community-dwelling older people with daily chronic non-malignant pain who were selected from a random sample of 1,000 older people in Melbourne. RESULTS: The use prevalence for the study group was 63% for analgesics and 39% for psychotropic medications, which is higher than the general older population without chronic pain (p < 0.00001). More women with chronic pain used analgesics, while psycho-social factors such as problems with sleeping and living at home alone were found to be associated with an increased use of psychotropic medications. CONCLUSION: A high proportion of community-dwelling older people with chronic non-malignant pain use analgesic and psychotropic medications. IMPLICATIONS: These findings provide the basis for further investigation into the level and appropriateness of analgesic and psychotropic medication use by older people with chronic pain.     

Anti-tumor ribonuclease, combined with or conjugated to monoclonal antibody MRK16, overcomes multidrug resistance to vincristine in vitro and in vivo

Onconase, a ribonuclease isolated from Rana pipiens oocytes and early embryos, is a member of the RNase A superfamily. Onconase has anti-neoplastic properties both in vitro and in vivo, and is undergoing clinical evaluation. In the present study, Onconase was combined with or conjugated to MRK16, an anti-P-glycoprotein (Pgp) monoclonal antibody. The interaction of these combinations with vincristine (VCR) against parental and multidrug resistant (MDR), Pgp expressing, human colon carcinoma cells caused increased VCR cytotoxicity in vitro and enhanced survival of athymic nude mice given transplants of drug resistant HT-29(mdr1) cells in vivo. The results suggest that combination treatment with Onconase and other agents that modulate the chemosensitivity of Pgp-expressing human tumor cells has the potential to overcome MDR.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Timed intercourse after intrauterine insemination for treatment of infertility

Objective: To compare the pregnancy rates, between intrauterine insemination (IUI) followed by timed intercourse and IUI only for treatment of the infertile couples. Study design: A prospective study of two different protocols of intrauterine insemination in two hundred and one infertile couples with a normal spermiogram was carried out. Of these, 101 couples were treated with IUI alone and 100 couples had both IUI and timed intercourse within a 12-18 h period. The pregnancy rates were compared between groups. Results: The characteristics of the two groups were similar in terms of the mean age, as well as the duration and causes of infertility. The cycle characteristics following follicular stimulation were also similar between two groups. The pregnancy rate per cycle increased with increasing numbers of total motile sperm per insemination in the IUI alone group (P=0.045). Timed intercourse increased pregnancy rate in patients with lower motile sperm number (<40×10⁶) (27.7% versus 10.5%, P=0.023), but not in patients with higher sperm number (≥40×10⁶) (25.7% versus 22.7%, P=0.671). Conclusions: In IUI with low number of motile sperm inseminated, timed intercourse significantly increases the pregnancy rates over IUI alone in infertile couples with a normal sperminogram. This alternative treatment appears to be a practical, simple, and inexpensive addition that improves the pregnancy rate in patients receiving ovulation induction and intrauterine insemination program.     

Neonatal clavicular fracture: clinical analysis of incidence, predisposing factors, diagnosis, and outcome

The objective of this study is to identify maternal, perinatal, and fetal risk factors for clavicular fracture in a single institution. We performed a prospective study of all deliveries during a 14-month period to identify confirmed cases of neonatal clavicular fracture. The control group consisted of the deliveries immediately preceding and following the index cases. Fifty-three cases of clavicular fracture were identified among the 4789 deliveries from October 1995 through November 1996 for an incidence of 1.11%. Three neonates in the clavicular fracture group were delivered through cesarean section. Neonates with fracture were significantly heavier at birth than those without (3564 vs. 3283 g, p <0.001), and had a lower mean head-to-abdominal circumference ratio (0.93 vs. 1.08, p <0.001), history of giving birth to a macrosomia (21 vs. 4%, p <0.05). The anterior shoulder was the predominant site of fracture (30/53). Fracture was detected mostly during the first 3 days of neonatal life (46/53). The outcome was benign, with complete recovery in all cases and no associated neurological sequelae. Neonatal clavicular fracture tended to be associated with neonatal somatometric characteristics and difficult deliveries. Considering the benign nature of this birth trauma, more invasive intrapartum management to lower its incidence is not advised.     

Feasibility Evaluation of an Interpersonal and Social Rhythm Therapy Group Delivery Model

The effectiveness of psychotherapies, such as interpersonal and social rhythm therapy (IPSRT), is supported by randomized controlled trials. These trials provide minimal direction regarding feasibility of psychotherapy delivery models. The study purpose was to identify factors facilitating implementation and sustainability of an IPRST group for patients with bipolar disorder. Qualitative data were assessed by the normalization process model (NPM). The results demonstrate feasibility of implementation with experienced clinicians, program coordination, and leadership support. Sustainability challenges include aftercare groups, space, and clinician time. The NPM provides a useful framework for evaluation of factors influencing the feasibility of psychotherapy delivery models.