Compact homogeneous Leviflat CR-manifolds.

We consider compact Leviflat homogeneous Cauchy-Riemann (CR) manifolds. In this setting, the Levi-foliation exists and we show that all its leaves are homogeneous and biholomorphic. We analyze separately the structure of orbits in complex projective spaces and parallelizable homogeneous CR-manifolds in our context and then combine the projective and parallelizable cases. In codimensions one and two, we also give a classification.

Teaching senior nurses how to teach communication skills in oncology.

Many nurses acknowledge that their nursing practice is hampered by inadequate teaching about communication skills during their nursing education. Ineffective communication has negative effects on patient care and causes stress when nurses interact with each other, with medical colleagues, with patients and their relatives. Many senior nurses teach junior staff about communication and feel uncertain about their competence to do so despite recognition of its importance. This article reports data from a training initiative endorsed by the Royal College of Nursing in the United Kingdom (UK) aimed at helping senior nurses to identify their personal strengths and weaknesses when communicating, learn new teaching methods and encourage new teaching initiatives. A residential 2-day course, based on learner-centered methods was employed. One hundred and twenty nine nurses from UK cancer centers worked on personal communication problems via group discussions, video demonstrations, small group teaching exercises and role-plays with professional actors. Post-course, participants reported significantly greater confidence in handling 14 common communication problem areas in cancer (p < .0001) and in 8 different areas of teaching. Participants were very enthusiastic about the course overall and especially valued the training approach and teaching materials provided. Three months post-course 91% reported changing their own teaching practice and 85% had initiated new communication skills teaching.

A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration.

OBJECTIVE: To evaluate the lifetime, response time, linearity, glucose range, and calibration stability of two different types of continuous glucose sensor implants in a dog model. RESEARCH DESIGN AND METHODS: Glucose sensors based on the enzyme electrode principle that are coupled to a radio transmitter were evaluated on the bench top, sterilized, and then implanted subcutaneously in nondiabetic mongrel dogs. A multichannel radio receiver and PC data processor were used to record the sensor glucose data. Initial early reliable sensor responsivity was recognized by a vigorous hyperglycemic excursion after an intramuscular injection of glucagon. Periodically the dogs were made temporarily diabetic by blocking pancreatic insulin secretion by subcutaneous injection of a synthetic somatostatin (octreotide). By using exogenous insulin injection followed by intravenous glucose infusion, glucose levels were manipulated through the entire clinical range of interest: 2.2-38.9 mmol/l (40-700 mg/dl). Every 5-10 min, reference blood glucose samples were obtained and run in our hospital clinical laboratory. The glucose sensor data was evaluated by linear least squares optimization and by the error grid method. RESULTS: Beginning as early as postimplant day 7, the in vivo performances of sensors were evaluated by using glucose infusion studies performed every 1-4 weeks. Bench-top and in vivo 90% response-time sensors were in the range of 4-7 min during sensor lifetime. Best-performing sensors from both types are summarized as follows. The earlier-stage technology was less linear with a dynamic range of no more than 22 mmol/l glucose, had a best-case recalibration interval of 18 days, and had a maximum lifetime of 94 days. The improved later-stage technology sensors, which were constructed with the addition of bioprotective and angiogenic membranes, were linear over the full extended range of clinical interest (2.2-38.9 mmol/l [40-700 mg/dl glucose]), had a best-case recalibration interval of 20 days, and had a maximum lifetime of >160 days. CONCLUSIONS: Stable clinically useful sensor performance was demonstrated as early as 7 days after implantation and for a sensor lifetime of 3-5 months. This type of subcutaneous glucose sensor appears to be promising as a continuous and painless long-term method for monitoring blood glucose. Specifically sensors with top-layer materials that stimulate angiogenesis at the sensor/tissue interface may have better dynamic measurement range, longer lifetimes, and better calibration stability than our previously reported sensors.

A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E.

A major focus in gene therapy has been the use of recombinant viruses to deliver genes in vivo. Although this approach shows much promise, there are many safety concerns associated with the use of viral materials in the treatment of human diseases. Our alternative cell-based gene therapy approach utilizes endothelial cells (Pro 175) isolated from the murine embryonic yolk sac. These endothelial cells were evaluated for their potential use in gene therapy as a gene delivery platform. As a test model, we used these cells to deliver apolipoprotein E (apoE) in the murine apoE knockout atherosclerosis model. The lack of apoE protein in these animals results in high levels of serum cholesterol and formation of severe aortic plaques and lesions at a young age. After transplantation of the apoE secreting Pro 175 endothelial cells into apoE-deficient mice, serum cholesterol levels were measured at 2 week intervals. During the 3 months after the initiation of these experiments, levels of cholesterol in the animals having received the apoE secreting endothelial cells were statistically lower compared with the levels of age-matched controls having received non-secreting endothelial cells. Concomitant with cholesterol reduction, atherosclerotic aortic plaques were noticeably reduced in the experimental apoE+ animals. These results highlight the potential of these unique endothelial cells as an efficient delivery platform for somatic gene therapy.

Role of endothelium in the control of mouse yolk sac stem cell differentiation.

Studies in our laboratory have shown that as early as day 8.5 of development, mouse yolk sac cells can generate T cells when placed in a thymic microenvironment. At this stage, yolk sac cells can also differentiate into myeloid cells in vitro. B cell differentiation in vitro was achieved with day 9 yolk sac by providing a bone marrow stromal feeder layer. We have now established endothelial cell lines and clones from yolk sacs of day 8-12 mouse embryos. These vary in their ability to support stem cell maintenance and differentiation. Our principal work has been carried out with day 12 cloned endothelial cell lines. One clone supported the > 100 fold expansion of yolk sac hematopoietic stem cells that subsequently could generate B cells, T cells and myeloid cells both in vitro and in vivo. Preliminary experiments with endothelial cells from younger embryos are also described.

A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors.

An implantable potentiostat-radiotelemetry system for in vivo sensing of glucose is described. An enzyme electrode sensor measures the oxidation current of hydrogen peroxide formed by the stoichiometric conversion of glucose substrate and oxygen cofactor in an immobilized glucose oxidase layer. The sensor current is converted to a frequency and transmitted at programmable intervals (4, 32, 256 s) to a remote receiver. Low power CMOS circuitry is employed and device operation for up to 1.5 years is predicted using two series connected 250 mAh lithium cells. Crystal controlled RF frequencies uniquely identify each sensor allowing over 10 sensors within the same 10 m radius. A custom interface card allows a PC to program the receiver and handle the transmitted sensor data using software written in Microsoft C and QuickBasic. Software control allows on-the-fly sensor addition or subtraction to the sensor group being monitored. Over 10 sensors can be tracked long-term using the longest transmit interval, or four sensors can be tracked during short-term infusion studies when the transmit interval is reduced to 4 s. The design, construction, operation, and performance of the system hardware and software are described and evaluated.

Evaluation of a subcutaneous glucose sensor out to 3 months in a dog model.

OBJECTIVE: To advance the feasibility of an implantable long-term glucose sensor with bioprotective sensor membranes and test protocols using a somatostatin analog (octreotide). RESEARCH DESIGN AND METHODS: Implantable sensors were constructed with one of eight bioprotective membranes and screened in vitro for stable response to glucose. Sensors were implanted subcutaneously into nondiabetic mongrel dogs and monitored at 4-min intervals via radiotelemetry. When implanted sensor responses showed evidence of tracking blood glucose after glucagon challenge (8-21 days postimplant), a glucose infusion protocol was used to assess performance. Sensor data were collected every 4 s after octreotide inhibition of endogenous insulin release. Reference plasma glucose samples were taken every 4-10 min. RESULTS: Preimplant in vitro testing of sensors verified linearity to 33.3 mM glucose and response times to 90% of equilibrium in 2-7 min. Ten implanted sensors tracked glucose for 20-114 days, during which 25 separate glucose infusion studies were conducted. The resulting regression data yielded a mean slope of 0.99 +/- 0.06, an intercept of 0.24 +/- 0.53 mM glucose, and a correlation coefficient 0.98 +/- 0.01. Long-term sensor stability was not judged adequate for clinical application, although two sensors tracked within +/- 15% for 33 and 42 days. In vivo oxygen delivery was shown to affect sensor performance. On explant, two of eight tested bioprotective membranes were found to be biostable and to fully protect the sensor's enzyme membrane. The foreign body capsule was adequately vascularized adjacent to the sensor up to 91 days postimplant. Sensor units eventually failed because of electronic problems (package leakage) or because of biodegradation or biofouling of test bioprotective membranes. CONCLUSION: Further development of this type of sensor may provide diabetic patients with a better means of monitoring blood glucose.

Enzymatic glucose sensors. Improved long-term performance in vitro and in vivo.

We studied the long-term in vitro and in vivo performance of enzyme electrode glucose sensors. Single commercially produced enzyme-active membranes remained functional for estimating glucose in vitro for 14-36 months. These membranes were implanted subcutaneously in rats for 1 year and, upon explanation, remained functional for measuring glucose in vitro. Sensors with these membranes plus an additional outer membrane with lower glucose permeability allowed glucose monitoring in the low oxygen tension of subcutaneous tissue. These sensors were surgically implanted in three nondiabetic dogs. Each sensor implant was coupled to a radio transmitter to allow continuous long-term glucose monitoring in these awake unrestrained dogs. In vivo sensor performance was evaluated by intravenous glucose infusion, with reference blood glucose determinations made in the clinical laboratory. These subcutaneously implanted sensors tracked changes in plasma glucose for up to 12 weeks. The in vivo initial response for three sensor implants was approximately 35 sec (n = 8). Sensor peak response to glucose after bolus infusion ranged from 3 to 14 min. Stability of sensor sensitivity within +/- 15% for more than 1 month was demonstrated in two of the dogs. Sensor lifetime was limited not by loss of enzyme activity, but by biodegradation of the outermost polyurethane membrane. The findings suggest that long-term continuous monitoring of blood glucose using a subcutaneously implanted enzyme electrode sensor may be possible.

Emetine myopathy in a patient with an eating disorder.

OBJECTIVE: To alert physicians to the dangers of a readily available, non-prescription drug by describing the clinical and pathological features of myopathy due to chronic poisoning with ipecac syrup in a patient with an eating disorder. CLINICAL FEATURES: A 27-year-old woman presented in 1991 with a right foot drop, followed a few months later by progressive severe neck and limb weakness associated with dysphagia, faecal incontinence and diffuse body ache. It emerged that she had been consuming increasing quantities of ipecac syrup (up to 200 mL per week) for three months to induce vomiting and weight loss. The serum creatine kinase activity was slightly elevated and electromyographic examination results were in keeping with a necrotising proximal myopathic process. Muscle biopsy showed vacuolar degeneration with myofibrilolysis and fine cytoplasmic body formation, consistent with a diagnosis of emetine myopathy. INTERVENTION AND OUTCOME: The patient was advised to stop taking ipecac and observed for the next few months. The symptoms resolved gradually and strength returned to normal in four months. CONCLUSION: Chronic emetine toxicity, with its potentially catastrophic consequences, should be remembered in the evaluation of neuromuscular symptoms in young women, in whom eating disorders are common and often unrecognised.

HTLV-I associated myelopathy in a Seychellois immigrant.

OBJECTIVE: To describe the clinical and laboratory features of human T-lymphotropic virus type I (HTLV-I) associated myelopathy in an immigrant from the Seychelles. CLINICAL FEATURES: A slowly progressive myelopathy has been recently diagnosed in a 64-year-old woman who emigrated to Australia from the Seychelles in 1957. Sphincter disturbance and back pain were the first manifestations, followed by gait disturbance. Neurophysiological investigation supported the clinical diagnosis of a myelopathy and radiological investigations revealed no structural cause. Serum antibodies to HTLV-I were detected by enzyme-linked particle agglutination and the presence of antibodies to individual HTLV-I gene products in the serum was confirmed by western blot. The virus was detected in a culture of the patient's peripheral blood mononuclear cells by antigen capture assay and by sequencing a polymerase chain reaction product amplified from the env gene. INTERVENTION AND OUTCOME: The patient was advised of the nature and prognosis of her illness. Oral corticosteroids were tried without benefit. CONCLUSIONS: The prevalence of HTLV-I infection is low in Australia although it may be endemic in some Aboriginal communities. Most infections are asymptomatic but the chronic neurological disease associated with HTLV-I infection has now been shown to exist in this country. HTLV-I infection should be considered in the aetiology of myelopathy without another obvious cause.

A positive coping strategy. Humour in the oncology setting.

Humour is an integral part of most positive human relationships, and does much to bring people closer together. Used sensitively and tactfully, it has much to offer patients and nurses in an oncology setting.

Cellular effects of piezoelectric versus electrohydraulic high energy shock waves.

High energy shock waves produced by a piezoelectric lithotripter, (EDAP LT.01) and an electrohydraulic lithotripter, (Dornier HM3) were examined for their effects on Chinese hamster ovary cells in suspension. The EDAP caused acute lactate dehydrogenase release, consistent with severe membrane disruption in a proportion of cells, with the remaining proportion of cells replicating normally as measured by clonogenic assay. Similarly, the Dornier also caused lactate dehydrogenase release. However, a significant proportion of cells which remained "viable" after Dornier treatment, (intact to lactate dehydrogenase), did not replicate by clonogenic assay. The Dornier HM3 lithotripter has been reported to produce free radicals in aqueous solution. In the current investigation, we could not detect significant free radical formation from the EDAP LT.01. Chinese hamster ovary cell killing by the Dornier HM3 was significantly augmented by radiosensitizers, 5-iodo-2-deoxyuridine or buthionine sulfoximine, while radioprotectors cysteamine and WR-1065 had no protective effect. EDAP cell killing was not influenced by either radioprotectors or radiosensitizers. The mechanism of in vitro cytotoxicity differs between piezoelectric and electrohydraulic high energy shock wave delivery.

Thrombolytic therapy in vertebrobasilar occlusion.

Since 1983 at the Alfred Hospital 4 patients with thrombotic or embolic vertebrobasilar occlusions have been treated with intra-arterial streptokinase (SK) infusions for the effects of persisting brainstem ischaemia despite anticoagulation with heparin. In 3 cases there was immediate and dramatic neurological improvement, in all cases associated with arteriographically demonstrated reperfusion of a blocked vessel. Two of these patients suffered further thromboembolic vertebral or basilar artery occlusions (3 days and 2 years later) but recovered fully without further thrombolytic therapy. The other patient was given intra-arterial SK 12 days after an apparently completed brainstem stroke: the therapy failed to cause reperfusion of a vertebral occlusion or produce any clinical improvement. Complications from the therapy were nausea requiring the termination of the SK infusion in one case, easily controlled bleeding from a recent surgical wound, and a clinically insignificant haemorrhagic transformation of cerebellar infarction in a third. The benefits of thrombolytic therapy in vertebrobasilar ischaemia and the dose of streptokinase required are discussed.

Intraventricular infusion of Dopamine in Parkinson's disease.

A patient with severe end-stage Parkinson's disease and troublesome fluctuations in motor function was treated with a long-term intraventricular infusion of dopamine. There was modest improvement in speech and mentation and there was smoother control of motor symptoms that was superior to that achieved by conventional oral medications.

Obstructive hydrocephalus caused by multiple sclerosis.

A case is reported of obstructive hydrocephalus secondary to the mass effect of a plaque of acute demyelination in the brainstem. The literature on the CT scan appearances in multiple sclerosis is briefly discussed in relation to this case.

Progression from MERRF to MELAS phenotype in a patient with combined respiratory complex I and IV deficiencies.

Identical twins developed myoclonic epilepsy in their teens. One twin remained mildly affected but the other went on to develop sensorineural deafness and ataxia with lactic acidosis and ragged red fibres leading to a diagnosis of mitochondrial encephalopathy. Multiple stroke-like episodes with hemiparesis followed, indicating progression from a MERRF to a MELAS phenotype. Biochemical studies revealed a severe deficiency of mitochondrial NADH-ubiquinone reductase and a moderate deficiency of cytochrome aa3. Western immunoblotting experiments using polyclonal antibodies raised against human placental cytochrome oxidase identified a similar profile of bands to those seen in controls, supporting the view that cytochrome aa3 deficiency in this case may be a secondary consequence of a failure of assembly related to a severe proximal respiratory chain defect.

Transient ischaemic attacks: controversies in treatment. A review.

The methods available to treat transient ischaemic episodes and to prevent stroke are discussed, with particular reference to the use of aspirin.