1-[3-(2-Benz-yloxy-6-hy-droxy-4-methyl-phen-yl)-5-[3,5-bis-(tri-fluoro-meth-yl)phen-yl]-4,5-di-hydro-1H-pyrazol-1-yl]propane-1-one.

In the title compound, C28H24F6N2O3, the mean plane of the central pyrazoline ring forms dihedral angles of 2.08 (9) and 69.02 (16)° with the 2-benz-yloxy-6-hy-droxy-4-methyl-phenyl and 3,5-bis-(tri-fluoro-meth-yl)phenyl rings, respectively. The dihedral angle between the mean planes of the pyrazoline and 3,5-bis-(tri-fluoro-meth-yl)phenyl rings is 68.97 (9)°. An intra-molecular O-H⋯N hydrogen bond is observed, which forms an S(6) graph-set motif. In the crystal, pairs of weak C-H⋯F halogen inter-actions link the mol-ecules into inversion dimers while molecular chains along [100] are formed by C-H⋯O contacts.

3-(2-Chloro-3-hy-droxy-4-meth-oxy-phen-yl)-1-(4,5-dimeth-oxy-2-methyl-phen-yl)prop-2-en-1-one.

The title compound, C(19)H(19)ClO(5), is a chloro derivative of a biologically significant chalcone family. The mean plane of the two substituted benzene rings are twisted by 55.33 (8)° with respect to each other. An intra-molecular C-H⋯Cl hydrogen bond generates an S(5) graph-set motif. In the crystal, a bifurcated O-H⋯(O,O) hydrogen bond leads to an R(1) (2)(5) graph-set motif and to the formation of zigzag chains propagating along the c-axis direction. A weak π-π inter-action involving the methyl-phenyl rings [centroid-centroid distance = 3.8185 (10) Å] and C-H⋯π inter-actions also occur.

Ethyl 2-amino-1-(4-fluoro-phen-yl)-5-oxo-4,5-di-hydro-1H-pyrrole-3-carboxyl-ate: crystal structure and Hirshfeld surface analysis.

In the title mol-ecule, C12H13FN2O3, the central pyrrole ring makes a dihedral angle of 9.2 (3)° with the eth-oxy carbonyl moiety whereas the fluoro-phenyl ring is rotated by 67.6 (2)° from the pyrrole ring. Supra-molecular aggregation is due to off-centric π-π stacking inter-actions involving screw-related pairs of mol-ecules, which are further connected by N-H⋯O and C-H⋯O inter-actions, forming a sinusoidal pattern along the [001] direction on the bc plane. Three-dimensional Hirshfeld surface analysis and two-dimensional fingerprint plots confirm the contributions of these inter-actions.

Development of a rapidly computable descriptor of prostate tissue temperature during transurethral conductive heat therapy for benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a condition in older men in which the mass of tissue in the prostate gland gradually increases over the course of many years, ultimately leading to urinary outflow obstruction. Current treatment of this condition is to surgically remove the obstructing tissue. One novel alternative therapy being studied is transurethral thermocoagulation of excessive prostatic mass. In this approach, a heat-emitting catheter is placed in the prostatic urethra, and the intraprostatic segment of the catheter is heated to temperatures above 60 degrees C for one hour. Two-dimensional cylindrical-co-ordinate computer simulations of this treatment modality were run to model resultant temperature distributions within the prostate gland and surrounding tissues. The simulations revealed that resultant tissue temperature changes were related directly to the power delivered to the catheter and inversely to the rate of blood perfusion. Further analysis of the temperature profiles produced a rapidly computable predictor of tissue temperature in the radial dimension. Using the predictor, a 'kill radius' around the prostatic urethra can be easily computed on-line, during treatment, from clinically available data, catheter power and catheter temperature. The computed kill radius may serve as a useful predictor of the extent of thermal devitalization of unwanted obstructing tissue and the long-term success of the treatment in relieving urinary outflow obstruction without surgery.

Computer-aided design and evaluation of novel catheters for conductive interstitial hyperthermia.

Conductive interstitial heating is a modality in which heating elements are implanted directly into the treated tissue. One implementation of such therapy employs electrically heated catheters that are implanted in staggered, parallel rows. To explore strategies for maximising the uniformity of tissue temperature distributions achieved with heated catheters, a two-dimensional computer model with cylindrical co-ordinates was used to evaluate radially and longitudinally the temperature distributions produced by a typical interior catheter surrounded by other similar catheters. Insights from the computer model led to new designs for catheters containing multiple heating elements that produced more uniform thermal distributions, eliminating previous 'cold spots' within the treatment volume located near the ends of the catheter. The new catheter designs also include compartments for the optional placement of radioactive seeds for simultaneous thermoradiotherapy.

Droop: a rapidly computable descriptor of local minimum tissue temperature during conductive interstitial hyperthermia.

Although the goal of local hyperthermia therapy for cancer is to elevate the temperature of a tumour to cytotoxic levels, without the presence of 'cold spots', varying blood flow has made the achievement of consistent, therapeutic temperature distributions extraordinarily difficult. The paper presents a novel approach to estimating local minimum tumour temperatures during conductive interstitial hyperthermia which facilitates identification and elimination of cold spots. Conductive interstitial hyperthermia is modelled mathematically for a parallel array of implanted, electrically heated catheters which warms the treated tissue by thermal conduction and blood perfusion. Computer simulations employing the bioheat transfer equation reveal a predictive relationship between implanted catheter temperature, catheter power, implantation geometry and local minimum tumour temperature. Formulation of this relationship in terms of a parameter named 'droop' allows estimation of local minimum intratumoural temperatures from individual catheter temperature and power. Computer simulations are also performed to determine the sensitivity of the droop-based estimator to variations in properties of the tissue and catheters. Generally, variations in geometry or thermal properties of about 10 per cent cause estimation errors of less than 1 degree C in magnitude. These results suggest that online estimates of thermal 'droop' may provide a practical route to more consistent control of intratumoural minimum temperature during conductive interstitial heat therapy.

Design and evaluation of closed-loop feedback control of minimum temperatures in human intracranial tumours treated with interstitial hyperthermia.

The dynamic nature of blood flow during hyperthermia therapy has made the control of minimum tumour temperature a difficult task. The paper presents initial studies of a novel approach to closed-loop control of local minimum tissue temperatures utilising a newly developed estimation algorithm for use with conductive interstitial heating systems. The local minimum tumour temperature is explicitly estimated from the power required to maintain each member of an array of electrically heated catheters at a known temperature, in conjunction with a new bioheat equation-based algorithm to predict the 'droop' or fractional decline in tissue temperature between heated catheters. A closed loop controller utilises the estimated minimum temperature near each catheter as a feedback parameter, which reflects variations in local blood flow. In response the controller alters delivered power to each catheter to compensate for changes in blood flow. The validity and stability of this estimation/control scheme were tested in computer simulations and in closed-loop control of nine patient treatments. The average estimation error from patient data analysis of 21 sites at which temperature was independently measured (three per patient) was 0.0 degree C, with a standard deviation of 0.8 degree C. These results suggest that estimation of local minimum temperature and feedback control of power delivery can be employed effectively during conductive interstitial heat therapy of intracranial tumours in man.

Detection of ventricular fibrillation with a ventricular monopolar catheter electrode.

This report describes the use of right ventricular impedance (RVZ) sensing with a monopolar electrode to identify the cessation of pumping with the onset of ventricular fibrillation. RVZ, ECG (lead II), and femoral artery pressure were monitored in seven anesthetized dogs. An impedance recorder (10-kHz, 100-microA peak-to-peak current) was used to measure RVZ between a monopolar, catheter-mounted electrode placed in the right ventricle and an indifferent electrode (8.5-cm diameter plate) sutured to the right chest wall. The catheter electrode was either 0.4 cm or 1.2 cm long and had a surface area of 0.50 cm2 or 1.50 cm2, respectively. A monopolar electrode was positioned at the apex of the right ventricle or midway between the apex and the tricuspid valve. The peak-to-peak amplitude of the pulsatile cardiac-induced impedance change was measured prior to and throughout an episode of ventricular fibrillation lasting up to 1 minute. On the average, the amplitude of the pulsatile RVZ signal after 10 seconds of fibrillation decreased by 79% of the prefibrillation amplitude. The 1.2-cm electrode located at the middle of the ventricle showed the largest reduction in pulsatile impedance, the amplitude being very small at 10 seconds. It is concluded that sensing RVZ by a monopolar electrode located on a catheter in the mid-ventricle can provide the mechanical information needed to identify the onset of ventricular fibrillation.

A computer-based, automated, telephonic system to monitor patient progress in the home setting.

In this report we describe an automated, telephonic system to monitor the progress of patients convalescing at home. The system includes a computerized central station that is capable of automated voice communication over the telephone, using voice reproduction, and touch-tone recognition. Peripheral hardware in multiple monitored homes need include only a touch-tone telephone, but may also be augmented by inexpensive, rudimentary diagnostic aids, such as a scale for body weight, a thermometer, or a blood pressure cuff and manometer. Current central hardware includes a NeXT computer, a fax modem, and a specialized telecommunications modem developed specifically for voice telecommunication using the NeXT. The central station acts like a robotic nurse in that it asks patients a series of questions and records the responses. The subjective questions to be asked are patient individualized and pre-selected by the physician from a question menu including items targeted specifically for the patient's disease or condition. In addition, clinical data such as body weight, blood pressure, and body temperature obtained from in-home diagnostic aids may be transmitted to the central station over the telephone using touch tones. The time-of-day and frequency of calling are pre-selectable, according to the patient's preference and clinical status. Data obtained by the central station can be easily accessed by the duty nurse via menu driven software. Reports depicting significant responses as a function of time are generated in graphical format to facilitate rapid identification of adverse trends. Hard copy reports can be dispersed directly by fax. Results from a pilot study show patients with cardiac disease readily use the system without difficulty or complaints. In one patient a five pound increase in body weight was detected, which prompted the patient's cardiologist to adjust his medication. In this way automated telephone follow-up can provide early detection of complications before they become severe, making the home environment safer and more secure for convalescence and contributing to reduced health-care costs.

Tracking cardiac output by a saline dilution technique using esophageal catheter electrodes.

This paper presents preliminary results of a study in which saline indicator dilution curves were obtained by measuring impedance dilution curves using a tetrapolar catheter-based electrode placed in the esophagus of anesthetized dogs. Cardiac output (CO) was calculated from the area under the impedance-derived saline dilution curve, and compared to CO calculated from the saline dilution curve obtained by a cylindrical external conductivity cell placed in an arterio-venous shunt. The results revealed an approximately two-third overestimation in CO determined using the esophageal electrodes. However, the esophageal impedance CO tracked CO determined by the conventional indicator dilution method very well. When the data were pooled, a cumulative correlation coefficient of 0.96 was obtained. Although the esophageal impedance CO method overestimates CO, it tracks changes in CO well. Further investigation is indicated to determine an optimal electrode configuration for the tetrapolar esophageal electrode.

Effective estimation and computer control of minimum tumour temperature during conductive interstitial hyperthermia.

The goal of heat therapy in the treatment of malignant disease is to raise the temperature of all neoplastic tissue to a cytotoxic temperature for a predetermined period of time. This seemingly simple task has proved difficult in vivo in part because of non-uniform power absorption and in part because of non-homogeneous and time-varying tumour blood flow. We have addressed this difficulty first by utilizing the conceptually simple technique of conductive interstitial hyperthermia, in which the tumour is warmed by multiple, electrically heated catheters, and second by implementing on-line control of minimum tumour temperatures near each catheter, estimated on the basis of the steady-state ratio of catheter power to catheter temperature rise. This report presents an analysis of the accuracy, precision, and stability of the on-line minimum temperature estimation/control technique for 22 patients who received 31 separate courses of conductive interstitial hyperthermia for the treatment of malignant brain tumours, and in whom temperature was monitored independently by 12-16 independent sensors per patient. In all patients the technique was found to accurately and precisely estimate and control the local minimum temperatures. Comparison of measured and estimated temperatures revealed a mean difference of 0.0 +/- 0.4 degrees C for those sensors within 1.0 mm of the expected location for minimum temperatures. This technique therefore offers an attractive method for controlling hyperthermia therapy-even in the presence of time varying local blood flow.

The evaluation of five specialized support surfaces by use of a pressure-sensitive mat.

This study used two full-size pressure-sensitive mats to evaluate five patient support surfaces. The mats, containing 1,536 and 2,340 pressure measurement sites, respectively, made it possible to quantify the entire interface pressure distribution of each support surface. Measurements for groups of 64 and 32 subjects were obtained in supine positions of 0 degree, 30 degrees, at maximal head elevations (50 degrees-60 degrees), and at lateral recumbency. Several statistical descriptors were calculated to characterize the interface pressure distributions. The support surfaces tested included: a powered-air overlay (ACUCAIR Continuous-Air-flow System), a low-airloss bed (FLEXICAIR MC3 Low-Airloss Therapy), a continuous lateral-rotation low-airloss bed (RESTCUE Dynamic Air Therapy), an air-fluidized bed (CLINITRON II Air-Fluidized Therapy), and an integrated bed (prototype Advance 2000 Bed). An analysis of variance revealed that the interface pressure was significantly lower and weight-bearing area was significantly higher on the five surfaces, when compared to the standard hospital mattress.

Accuracy and precision of computer-simulated tissue temperatures in individual human intracranial tumours treated with interstitial hyperthermia.

Accurate knowledge of tissue temperature is necessary for effective delivery of clinical hyperthermia in the treatment of malignant tumours. This report compares computer-predicted versus measured intratumoral temperatures in 11 human subjects with intracranial tumours, treated with a conceptually simple 'conductive' interstitial hyperthermia system. Interstitial hyperthermia was achieved by the use of parallel arrays of implanted, electrically heated catheters. The tissue was warmed by thermal conduction and blood convection. Simulation of intratumoral temperatures was achieved by solving a modified bioheat transfer equation on a digital computer using a finite difference method. Comparison of intratumoral temperatures from simulations and measured values differed by about +/- 0.75 degrees C. Further analysis of computed temperature distributions between catheters revealed a rapidly computable relationship between the local minimum tumour temperature and nearby catheter power and temperature that accounts for effects of varying blood flow. These findings suggest that 'on-line' prediction and control of local minimum tumour temperatures are feasible with the conductive interstitial technique.