[Intramedullary cervical abscess: a case report and literature review]. / Intramedullyarnyi abstsess sheinogo otdela spinnogo mozga: klinicheskii sluchai i obzor literatury.

Intramedullary abscesses of the spinal cord are the rarest form of infectious lesions of the central nervous system. We report surgical treatment of a patient with intramedullary cervical abscess caused by L. monocytogenes. Features of this case are absence of primary purulent focus and atypical infectious agent. The patient underwent surgical treatment for intramedullary cervical abscess and subsequent antimicrobial therapy. Subtotal regression of neurological symptoms was noted in early postoperative period. The authors emphasize strict collegial decision-making regarding diagnosis of this disease and choice of optimal treatment strategy.

[Treatment of malignant peripheral nerve sheath tumors: case reports and a literature review]. / Lechenie zlokachestvennykh opukholei obolochek perifericheskikh nervov: sluchai iz praktiki i obzor literatury.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that develop from peripheral nerve sheath cells (T. Hirose, B.W. Scheithauer). These tumors are characterized by aggressive growth with an unfavorable outcome and may develop de novo or through malignant transformation of schwannomas, neurofibromas, or ganglioneuromas. MPNSTs are characterized by a rapid course and a poor prognosis. In this article, we reported cases of patients with malignant peripheral nerve tumors of the brachial plexus trunks and spinal localization.

Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees C using a desiccator technique.

This study evaluated the ability of mutagenic antineoplastic agents to vaporize at room temperature (23 degrees C) and 37 degrees C. A bacterial mutagenicity assay was used to determine the mutagenicity of these agents in the vapor phase. Open plates of bacteria were exposed to varying amounts of drug solutions in sealed glass containers for 24h. The drug solutions were prepared as they would be for patient treatment and were tested at 0.25, 0.5 and 1.0 ml of each drug solution per 10 l of air. Following exposure, the plates exposed at 23 degrees C were incubated an additional 48 h at 37 degrees C to allow for expression of mutations. Those exposed at 37 degrees C were incubated for an additional 24h at 37 degrees C. Carmustine, cyclophosphamide, ifosfamide, thiotepa, and mustargen demonstrated vaporization at 37 degrees C. Carmustine and mustargen also demonstrated significant vaporization at 23 degrees C, while cyclophosphamide demonstrated a 50% increase in revertants at this temperature. In addition, sodium azide, a known mutagen used as a control was also mutagenic as a vapor at both temperatures. Doxorubicin, cisplatin, etoposide, 5-fluorouracil and mitomycin were not detected as vaporizing in this assay. The study found that vaporization of standard solutions of some antineoplastic agents is possible at room temperature and increases as the temperature increases. Therefore, vaporization of spilled antineoplastic agents may present an additional route of exposure to healthcare workers through inhalation.

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 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.

Prediction of pocket-portable and implantable glucose enzyme electrode performance from combined species permeability and digital stimulation analysis.

Development of enzyme electrode sensors can be facilitated by the use of computer simulation modeling techniques. In this work, the model accounts for contacting solution effects, changes in species diffusion and partition coefficients across multiple membrane layer interfaces, cofactor limitation effects, enzyme loading, enzyme kinetics and decay, and other variations in electrode layer geometry. Experimentally determined single species membrane permeabilities are included in the digital simulations to predict the performance characteristics of a multilayered glucose oxidase based enzyme electrode. Information obtained includes range of sensor linearity under different substrate and cofactor concentration combinations, sensor time response and output as permeability parameters and enzyme loading are varied, sensor washout and interference effects, and prediction of decay of sensor enzyme concentration and resultant estimated sensor lifetime as a function of contacting solution conditions and sensor permeability.

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.

Development and evaluation of a wearable blood glucose monitor.

Complex operation, prolonged set-up time, reliability problems, high cost, and excessive size limits the use of currently available extracorporeal continuous blood glucose analyzers. A self-calibrating, wearable blood glucose monitor has been developed to overcome these impediments. The wearable blood glucose monitor is a 410 g forearm-mounted instrument with three miniature pumps for blood sampling, calibration, and insulin infusion, and a flow cell containing an enzyme-electrode sensor capable of determining plasma glucose levels accurately and precisely in undiluted whole blood. The unit is connected to a computer controller with graphics display. Venous blood is drawn from a 21 gauge single lumen cannula through the sensor flow cell. A rate determination of glucose is completed in 20 sec and the blood is returned to the arm vein. Heparinized saline wash solution follows. No blood loss or significant systemic heparinization occurs. Cycle time is set from 2 to 5 min. The method is linear to at least 300 mg/dl glucose, independent of hematocrit, and free of interferences from blood constituents at normal venous pO2 with a coefficient of variation of 1-3% between calibrations. The sensor has a service life of at least 3 weeks. This wearable blood glucose monitor, with its high performance sensor, reduced size, and ease of operation, shows promise for evaluating and treating diabetes.

Laboratory evaluation of new reusable blood glucose sensor.

An enzyme-electrode sensor designed specifically for pocket-portable self-monitoring of blood glucose is described. The sensing device in this instrument is unique because it is reusable for at least 30 days, at which time it is easily replaced by placing a new enzyme-membrane cartridge over the electrode. As little as 7 microliters of undiluted whole blood, plasma, or serum is applied directly to the sensor, and glucose is automatically determined in 30 s. No manual timing or wiping step is required after sample application. On eight production instruments, plasma glucose concentration was determined (n = 20) at 57, 125, 246, and 347 mg/dl. The average coefficient of variation for the 80 determinations for each instrument ranged from 2 to 5%, averaging 3.7%. The instrument is inherently linear, independent of hematocrit, and without oxygen limitation when dissolved oxygen concentration is greater than 35 mmHg. No interferences were found from plasma constituents, heparin, or acetaminophen.

Facilitating intensive conventional insulin management using a manually operated syringe injector.

A manually operated 3-ml insulin catheter and syringe injector system was evaluated in 26 insulin-dependent ketosis-prone patients for a mean of 11 months per patient. Eighteen patients had normal kidney function, 5 had renal insufficiency (plasma creatinine 2.0-4.8 mg/dl) and 3 had successful kidney transplants. Regular insulin was infused 15-30 min before each meal. The subcutaneous route of delivery was used in all patients except the 3 renal transplant patients who received regular insulin intraperitoneally through a chronically placed intraperitoneal microbore catheter. Basal insulinization was obtained using subcutaneous long-acting insulin. Blood glucose control improved in all 3 groups of patients. Mean blood glucose decreased from 203 +/- 10-118 +/- 3 SEM; hemoglobin A1 decreased from 12.5 +/- 0.4-9.2 +/- 0.25 SEM (normal range 5-9%). We conclude that a manually operated syringe injector can be used to make multiple dose insulin management less painful and more convenient. The injector can be worn and activated beneath clothing and also worn while showering or swimming. Yet it can be removed while sleeping, when sexually active or when engaged in strenuous athletic activity.

Implanting the glucose enzyme electrode: problems, progress, and alternative solutions.

An implantable glucose sensor is needed before a reliable artificial pancreas can be realized. The principles and current status of one such device, the glucose enzyme electrode, is presented and discussed. While monitoring glucose this enzyme sensor consumes enough oxygen to become oxygen-limited. This problem has been solved by developing hydrophobic membranes that are more permeable to oxygen than to glucose. Two types of membranes with this property made from (1) cross-linked albumin and (2) sebacyl chloride (nylon) are described. Placing these membranes over the glucose enzyme electrode solves the problem of oxygen limitation. Furthermore, the addition of this type of membrane increases the linear response range of the electrode to glucose to include the entire clinical range of interest (0-400 mg/dl). Other problems in developing an implantable glucose sensor are discussed. Competing strategies to achieve an implantable artificial pancreas without using electronic or mechanical components are presented and evaluated.

Immobilized-enzyme rate-determination method for glucose analysis.

We present a rate-determination method for analyzing glucose. A glucose enzyme electrode serves as the sensor and is made by placing a gel-immobilized layer of glucose oxidase over the tip of a Clark-type O2 electrode. The electrode membrane is made of Teflon and is derivatized by etching with a suspension of colloidal sodium metal in organic solvent. The enzyme is coupled to the membrane surface by use of paraformaldehyde. The immobilized-enzyme method is compared with a similar solution-enzyme method and with the National Glucose Reference method. The immobilized enzyme method compares favorably with the solution-enzyme method and offers the advantages of simplicity, economy of enzyme, and linearity over a greater range of concentration.

Rotating disk membrane oxygenator based on transmembrane catalysis of hydrogen peroxide.

1) Oxygen transfer in the catalyst membrane oxygenator is not limited by diffusion through the blood-membrane boundary layer. Instead, oxygen transfer occurs at a rate independent of blood flow conditions and is evenly distributed over the membrane surface. Shear-induced mixing combined with high boundary O2 layer gradients are the mechanisms of transfer. 2) The rotating disk design provides very high level oxygen transfer. However, H2O2 concentration, blood flow rate, and disk rotation rate must be adjusted so that excess O2 supersaturation in the blood-membrane boundary does not lead to significant bubble formation. 3) The catalyst membranes used in the hemodialysis-based oxygenator have been industrially produced. 4) Effective CO2 transfer can be carried out across a hemodialysis type of membrane as previously reported. 5) The catalyst membrane oxygenator as studied in the dog performs well for 3-5 hrs, at which time inhibition of the catalyst leads to H2O2 breakthrough which causes methemoglobin formation. The mechanisms of catalyst inhibition and ways for its prevention are under study. 6) The catalyst membrane oxygenator offers the advantages of simultaneous artificial kidney treatment. This feature may be of help in maintaining acid-base balance and treating edema states.