The pharmacokinetics of gamma-glutamyl-L-dopa in normal and anephric rats and rats with glycerol-induced acute renal failure.

1. The pharmacokinetics of gamma-glutamyl-L-dopa (gludopa) and its metabolite, L-dopa, have been studied in normal rats at three dose levels of gludopa: 2 mg kg-1, 5 mg kg-1 and 7.5 mg kg-1. The extent of metabolism in normal rats, and the pharmacokinetics in anephric rats and rats with glycerol-induced acute renal failure (ARF) were also studied at a gludopa dose of 2 mg kg-1. 2. Gludopa was extensively metabolised to L-dopa with only about 10% of an injected dose being excreted unchanged. Normal rats had a rapid gludopa clearance of 50.9 +/- 9.6 ml min-1 kg-1 and elimination rate constant of 2.99 +/- 0.27 h-1. The mean residence time and half-life were 20.9 +/- 1.4 and 14.4 +/- 1.0 min, respectively. The apparent volume of distribution at steady state was 1.05 +/- 0.18 l kg-1. 3. No statistically significant differences were found in the main pharmacokinetic parameters between ARF and controls for either gludopa or its metabolite L-dopa. 4. In anephric rats and controls the kidneys were found to contribute about 68.5% and 67.2% to the elimination of gludopa and the metabolite L-dopa, respectively. 5. These results confirm that gludopa is an efficient pro-drug for L-dopa, and that the kidneys are the major site of gludopa metabolism. It seems likely that the renal specificity of gludopa persists in ARF.     

Flexion-distraction injuries of the lumbar spine and associated abdominal trauma

Recent experience with flexion-distraction injuries of the lumbar spine associated with blunt abdominal trauma and the use of a lap belt alone has caused us to review our experience over the last 7 years. Eighteen patients were identified, with an average age of 22 years, and an average followup of 34 months. Fifteen were involved in motor vehicle accidents, with 11 being single-vehicle accidents. Of note, 12 of the 15 were rear seat passengers with lap belts only. Twelve patients suffered abdominal injury, seven requiring operative intervention, mainly for hollow viscus injury. In three patients, a delay of 24 hours or more occurred before recognition of intra-abdominal pathology requiring surgical therapy. One patient had an unrecognized spinal fracture for 2 weeks after abdominal surgery for a perforated viscus. The spinal injury was carefully assessed and analyzed for prognostic factors. Six were graded excellent, five good, four fair, and one poor. One case of paraplegia associated with avulsion of the spinal cord from distraction is reported. Prognostic factors included the amount of facet joint involvement and the degree of initial kyphosis. Those having greater than 17 degrees of kyphosis had a poor prognosis. Early recognition of the constellation of injuries involving the spine and abdomen associated with the use of the lap belt is recommended with surgery to the spinal fracture as outlined.     

低脉压与晚期慢性心衰患者利钠肽和死亡率升高独立相关

目的:脉压(PP)升高一贯用来预测有心血管疾病危险患者和轻度慢性心衰(CH F)患者的心血管疾病发生率和死亡率增高。相反,PP降低与急性失代偿性心衰患者死亡率升高相关。然而,尚不清楚PP对于晚期CH F患者的预测价值。方法和结果:采用Cox比例风险回归分析研究了1901例N YH A III或IV级CH F患者(平均年龄65岁,平均射血分数26%)的资料,经校正其他危险因素后,分析PP对死亡率的影响。检测了1个亚组患者的利钠肽水平。多元Cox回归分析表明,PP降低与死亡率增高相关(每增加10m m H g的H R为0.91,95%CI0.93～0.99),这一相关性独立于平均…     

THE PSYCHOLOGICAL IMPACT OF HIP ARTHROPLASTY

The impact of total hip arthroplasty on psychological functioning was examined in 51 patients; 25 females and 26 males with a mean age of 65 years (range 42–81 years). Assessments of psychological well-being and distress were made with the Mental Health Inventory. Life satisfaction, self-rated health, and pain ratings were also obtained. Assessments were made prior to surgery, immediately after surgery, and at a 2 month follow-up. The operation produced significant improvements in psychological well-being (P < 0.001), psychological distress (P < 0.001). life satisfaction (P < 0.01), self-rated health (P < 0.001), and pain (P < 0.001). It is concluded that the changes in medical and functional status following hip arthroplasty documented in previous research are accompanied by substantial improvements in psychological state, and that the inclusion of psychological factors in hip arthroplasty research will provide a more comprehensive assessment of outcome.     

Gene therapy in soft tissue reconstruction

Gene therapy is defined as the introduction of a therapeutic gene into a cell, whose expression can lead to a cure of a disease or offer a transient advantage for tissue growth and regeneration. The delivery of genes can be undertaken for a number of purposes, usually it is attempted to enhance or add a function to a cell or a tissue or to delete or reduce another function. In this brief overview we describe various vehicles and techniques that have been developed to deliver therapeutic genes into cells, such as viral vectors and physical/chemical gene delivery methods including naked DNA and particle-mediated gene transfer, the microseeding technique and the application of lipids. Furthermore we review the potential utility of gene therapy from the perspective of a reconstructive surgeon. Several tissues will be discussed, particularly muscle, tendon, nerve, bone, skin and wounds.     

Timing of deletion of autoreactive V{beta}6+ cells and down-modulation of either CD4 or CD8 on phenotypically distinct CD4+8+ subsets of thymocytes expressing intermediate or high levels of T cell receptor

In this paper we describe a differentiation sequence amongst adult murine thymocytes which goes from CD4+8+3lo(low) to CD4+8+3int(intermediate) to CD4+8+3hi(high) and then to mature single positive CD3hi thymocytes. Phenotypic characterization of CD4+8+3int/hi cells for a number of other surface markers is consistent with them being in transition from CD4+8+3lo phenotype to mature phenotype. The same observation was made for sensitivity towards ionomycin-mediated apoptosis. In the thymus of Mls-1a mice, where autoreactive TCR-V beta 6+ cells are negatively selected, deletion of TCR-V beta 6+ cells was first detected in the CD4+8+3int subset, and was complete by the CD4+8+3hi stage, suggesting that up-regulation of the TCR/CD3 complex is required for deletion of Mls-1a autoreactive thymocytes. No sign of apoptosis was detected among any fresh thymocyte subsets suggesting that apoptotic cells are rapidly cleared from the thymus. The CD4+8+3int/CD4+8+3hi cells are therefore populations in transit from the typical cortical thymocytes to the mature T-cells.     

Patients' and family members' perspectives on the benefits and working mechanisms of family nursing conversations in Dutch home healthcare

The aim of this study is to propose a model of the benefits and working mechanisms of family nursing conversations in home healthcare from the perspective of participating patients and their family members. Family nursing conversations in this study are intended to optimise family functioning, improve collaboration between family and professional caregivers and ultimately prevent or reduce overburden of family caregivers. In a qualitative grounded theory design, data were collected in 2017 using intensive interviewing with participants of family nursing conversations in home healthcare. A total of 26 participants (9 patients and 17 family members) from 11 families participated in a family nursing conversation and the study. Seven nurses who received extensive education in family nursing conversations conducted them as part of their daily practice. Interviews occurred 4–6 weeks after the family nursing conversation. The model that was constructed in close collaboration with the families consists of three parts. The first part outlines working mechanisms of the conversation itself according to participants, i.e. structured and open communication about the care situation and the presence of all of the people who are involved. The second part consists of the benefits that participants experienced during and immediately after the conversation – an increased sense of overview and improved contact among the people involved – and the related working mechanisms. The last part consists of benefits that emerged in the weeks after the conversation – reduced caregiver burden and improved quality of care – and the related working mechanisms. Insight into the benefits and working mechanisms of family nursing conversations may assist healthcare professionals in their application of the intervention and provides directions for outcomes and processes to include in future studies.     

The Pittsburgh Sleep Diary

SUMMARY  Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12–31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 ( n = 39, P < 0.001).     

Psychological influences on the perception of immune function

BACKGROUND: Perception of deficiencies in immunity are common in a number of patient complaints. However, little is known about the way in which individuals form perceptions about the competence of their immune system. In two studies we examined the relationship between subjects' perceptions of their immune functioning, physical symptoms, mood and measures of immunity. METHODS: In Study 1, 20 healthy volunteers completed global ratings of their immune system functioning, as well as mood and symptom reports, twice a week for 5 weeks. At the same time, blood samples were taken to assess serum IgA, IgG, and IgM antibodies. In Study 2, another sample of 58 subjects completed the same measures weekly for 5 weeks and their blood was tested for concentrations of CD3, CD4, CD8, and CD16 lymphocytes. RESULTS: We found perceptions of immune functioning to be unrelated to the concentrations of serum antibodies or blood lymphocytes. Immune perceptions were strongly related to mood and in particular, feelings of fatigue and vigour. The experience of recent physical symptoms, while not as strong as mood variables, was also important in perceptions of immune functioning. CONCLUSIONS: Mood seems to be an important determinant in the perception of immune function, and complaints about immune dysfunction in clinical situation should be investigated with this possibility in mind.