Beam shaping for microwave waveguide hyperthermia applicators.

PURPOSE: Hyperthermia treatments commonly use single element microwave waveguide applicators. The microwave beam patterns produced by these applicators are often non-uniform. As a result, hot spots are formed in the heated tissue and therapeutic temperatures are reached in only small areas of the treatment field. We have constructed new coupling boluses that improve the heating patterns of external microwave applicators. METHODS: The microwave beam transmitted through the bolus is modified by microwave absorbing saline/gelatin pads. The pads can be designed to result in a uniform heating pattern over a large area or alternatively, complex heating patterns can be generated for specific clinical applications. An analysis of the effect of bolus design parameters on microwave absorption patterns is presented. The heating patterns of the MA-100 and MA-120 microwave waveguide applicators have been measured in muscle and fat phantom materials with both the manufacturer's boluses and the new boluses. RESULTS: In the case of the MA-100, the area above the 70% heating level measured in a muscle phantom was increased by a factor of 2.3 by an absorbing pad bolus. Similarly, the heating area of the MA-120 was increased by a factor of 2.6 by an absorbing pad bolus. The boluses were tested in a clinical setting by measuring tissue temperature profiles in patients under different bolus arrangements. The area over which therapeutic temperature was achieved was increased considerably when the absorbing bolus was used. A second bolus was designed for the MA-120 to produce a ring heating pattern for the treatment of a breast cancer patient who had developed recurrences at the periphery of a skin graft. The heating pattern produced in a muscle phantom is compared with tissue temperature profiles measured during the hyperthermia treatment of this patient. CONCLUSIONS: Microwave absorbing filters using saline pads significantly improve the heating patterns of microwave waveguide hyperthermia applicators. This improvement was confirmed in clinical application where much greater areas of homogeneous heating were observed. The technology was extended to produce complex heating patterns for special clinical applications.

Placebo-controlled trial of dexamethasone for chronic biliary pain after cholecystectomy.

Activation of the sympathetic nervous system appears to be relevant in some patients with unexplained pain after cholecystectomy, particularly those who show increases in plasma transaminase activity after challenge with morphine (morphine responders). In this study, the hypothesis that dexamethasone would improve chronic biliary pain, perhaps by suppressing activation of the sympathetic nervous system, was tested in a double-blind, placebo-controlled, cross-over trial in 20 patients, 10 morphine responders and 10 nonresponders. Before treatment with dexamethasone and placebo, urinary excretion of norepinephrine (NE) was significantly higher (p less than 0.05) in morphine responders than in nonresponders. During treatment with dexamethasone, 1 mg each night for 4 weeks, neither morphine responders nor nonresponders showed a significant improvement in pain or nausea or a significant reduction in sympathoadrenomedullary activity as assessed by urinary excretion of catecholamines. At the dose administered, dexamethasone was unhelpful for chronic pain after cholecystectomy and did not result in suppression of the sympathetic nervous system as assessed by urinary excretion of NE.

The reducible risks of sudden infant death syndrome (SIDS).

The general practitioner rarely encounters a case of SIDS in practice. However, every young parent fears such a tragedy. The authors explore known risks for a SIDS death which are reducible. In particular, the infant between 2 and 4 months of age is at greatest risk from factors relating to poverty and seasonality. Counselling parents about such risks is an important role for the general practitioner.

A 100 MHz B-scan ultrasound backscatter microscope.

The construction and operation of a 100 MHz B-mode ultrasound backscatter microscope are described. The powerful B-mode technique is extended into the domain of microscopy allowing the imaging of internal structure in living specimens on a microscopic scale. A frame rate of 5 frames per second is achieved which gives rapid feedback to the operator. Specially designed components of the scanner are described in detail, including the transducer, motion system and scan converter. An f/2 transducer is employed, leading to a scanner resolution of approximately 36 micron in both the lateral and axial directions. The benefits of such high resolution are demonstrated in preliminary images of multicellular spheroids and intact human ocular tissue.

The effect of renal and hepatic impairment and of spironolactone on digoxin immunoassays.

The effect of renal and/or hepatic dysfunction, and of concomitant spironolactone therapy, on seven commercial digoxin assays was evaluated in 45 patients taking both these drugs, and a comparison made with the digoxin concentrations measured using the same assays in 30 patients taking digoxin in the absence of spironolactone. The study showed that increasing renal dysfunction resulted in increasing inaccuracy in assay results with the methods tested. The influence of concomitant spironolactone was to produce a further distortion, which was shown to be additive in patients with impaired renal and/or liver function. The results highlight the unresolved specificity problems which persist in many, if not all, of the immunoassays currently offered to clinical laboratories which, if not recognised, could significantly influence digoxin therapy and patient management.

Population analysis of the pharmacokinetic variability of high-dose metoclopramide in cancer patients.

Metoclopramide infusions are used to prevent nausea and vomiting in cancer patients during chemotherapy. 47 patients received metoclopramide during 109 chemotherapeutic treatments as a loading (dose range = 0.55 to 4.5 mg/kg over 15 minutes) and maintenance (dose range = 0.57 to 4.8 mg/kg over 8 hours) infusion. During and up to 24 hours after the end of the maintenance infusion between 4 and 10 blood samples were collected per treatment. Metoclopramide was analysed in plasma by liquid chromatography. Pharmacokinetic and demographic data of 83 treatments were analysed by the NONMEM program using a linear 2-compartment model. It was found that bodyweight and serum alkaline phosphatase activity explain some of the interindividual variability in clearance (CL). The typical pharmacokinetic parameters for an average individual (70kg, alkaline phosphatase = 100 IU/L) were: CL = 20 L/h; volume of distribution at steady state (Vdss) = 190L; terminal half-life = 8h. The interindividual variabilities in clearance, volume of central compartment and Vdss were 50%, 35% and 35%, respectively. The residual variability in plasma concentrations was estimated as 13%.

Adverse reactions during intravenous urography: are these due to histamine release?

The effects of four different radiographic contrast media (Urovison 58%, Hexabrix 320, Iopamiro 370 and Omnipaque 300) have been examined with respect to histamine release, cardiovascular changes and adverse drug reaction (ADR) in a group of 200 patients undergoing intravenous urography. Each patient received only one of the four agents, which were allocated on a random basis. Urovison produced the greatest number of ADRs. Iopamiro caused the least. No significant correlation between the magnitude of the change in plasma histamine following injection of radiographic contrast medium and the production of a particular ADR could be demonstrated. Heart rate increased significantly following the administration of Urovison, Hexabrix and Iopamiro in the absence of any appreciable change in blood pressure. These results and our earlier findings would favour the use of the low-osmolality contrast media in intravenous urography to minimize ADRs, histamine release and patient discomfort.

A hypothesis concerning Clostridium perfringens type A enterotoxin (CPE) and sudden infant death syndrome (SIDS).

This study identifies the presence of Clostridium perfringens type A enterotoxin (CPE) in some gastrointestinal and serum samples from babies who had died of the Sudden Infant Death Syndrome (SIDS) and other causes. On occasion antibodies to this toxin were identified in sera. CPE is parasympathomimetic in its action. In the adult food poisoning model it is produced when the organism sporulates in vivo. This leads to speculation as to whether this toxin may play an ante-mortem role in the dying process of infants, either in the agonal stages or as a causative factor in SIDS.

Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers.

The pharmacokinetics and pharmacodynamics of prochlorperazine were studied in healthy volunteers using a recently developed h.p.l.c. assay. Eight subjects received 12.5 mg and 6.25 mg i.v. doses of prochlorperazine, a 25 mg oral dose and placebo in random order. Plasma half-life (t1/2) of prochlorperazine was 6.8 +/- 0.7 h and 6.9 +/- 0.8 h for the 12.5 mg and 6.25 mg i.v. doses respectively. Apparent volume of distribution and plasma clearance were high and the kinetics did not appear to be dose-related. Absorption of oral prochlorperazine appeared to be slow and bioavailability was very low. A metabolite, possibly prochlorperazine sulphoxide, was noted after oral dosing. Mild sedation was common after i.v. prochlorperazine, but cardiovascular effects were minimal. The main adverse effect was akathisia which was reported by five out of eight subjects after the higher i.v. dose. These results provide preliminary information on the pharmacokinetics of i.v. prochlorperazine which were previously unknown.

High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy.

We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophosphamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.

A flatness and calibration monitor for accelerator photon and electron beams.

A flatness monitor has been built to quickly and accurately check accelerator beam flatness and dose calibration. Consisting of a 7 X 7 ion chamber array, the unit operates in photon beams from 60Co energies to 25 MV and electron beams (scattered or scanned) from 6 MeV to 25 MeV.

Oral bioavailability of high-dose metoclopramide.

The oral bioavailability of high-dose metoclopramide was studied in 12 patients, who received oral or intravenous (i.v.) metoclopramide in random order with each of 2 consecutive courses of cytotoxic chemotherapy. The terminal half-life of metoclopramide was 7.1 +/- 0.4 h (mean +/- SEM) and was not affected by the route of drug administration. Mean bioavailability was 86.6 +/- 4.7% and the range (65-118%) was less than that reported for standard doses. Neither half-life nor bioavailability was significantly correlated with age. Adverse effects were mild and were similar for both oral and iv metoclopramide. Oral high-dose metoclopramide, given in the same doses as for i.v. administration, should therefore be as effective as the i.v. regimen and may be easier to administer.

The trained nurse in general practice.

A trained nurse is employed in a suburban general practice in South Australia to provide additional care for elderly patients at home. This nurse's observations, her assessments, the problems she encountered and the courses of action she took during 426 consecutive visits are reported and discussed. The cost of the visits is estimated.

Cryotherapy improves prurigo nodularis.

A 55-year-old black woman with an eight-year history of prurigo nodularis was treated successfully with blistering cryotherapy. Cryotherapy resulted in smooth macule formation and afforded extended relief of pruritus. Several standard modalities of treatment had been used previously and had resulted in only partial relief of symptoms and minimal reduction of nodule size. This case demonstrates that cryotherapy can be a useful therapeutic alternative for prurigo nodularis.