Intratumour factors influencing the access of antibody to tumour cells.

The histological structure and biochemical composition of human tumours is very varied, as is the structure of the microvascular network. It can be expected, therefore, that the extravasation, diffusion and convection of macromolecules will vary between tumours - and also between areas in the same tumour. The major factors influencing the intratumour distribution of injected antibody are reviewed and an attempt made to identify the tumour types in which therapeutic antibody, with or without a cytotoxin, will distribute most effectively.

Distribution of injected monoclonal antibody in lymphoma-infiltrated spleen.

Specific and non-specific antibody was injected into mice with lymphoma-infiltrated spleens in order to assess the distribution with both time and with extent of tumour infiltration. The specific antibody (MRC OX7) bound to the Thy 1.1 antigen on the lymphoma cells (A120).

Toxicity of astatine-211 in the mouse.

The toxicity of the alpha particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

Relative concentration of astatine-211 and iodine-125 by human fetal thyroid and carcinoma of the thyroid in nude mice.

The concentrations of 211At and 125I were measured in various tissues in nude mice bearing xenografts of human thyroid tissue (fetal and malignant). The relative concentration of the two halogens was obtained at 4 and 24 h after injection. Samples were taken of the host blood, muscle and thyroid gland and the grafted tissues.

Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest.

The automatic external defibrillator is a simple device that can be used by nonprofessional rescuers to treat cardiac arrest. In 1287 consecutive patients with out-of-hospital cardiac arrest, we assessed the results of initial treatment with this device by firefighters who arrived first at the scene, as compared with the results of standard defibrillation administered by paramedics who arrived slightly after the firefighters. Of 276 patients who were initially treated by firefighters using the automatic defibrillator, 84 (30 percent) survived to hospital discharge (expected rate according to a logistic model, 17 percent; P less than 0.

An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial.

Purpose: Percutaneously inserted central venous catheters are widely used. Catheter-related bacteremia or fungemia is the most frequent serious complication of these catheters. In an attempt to reduce the frequency of such infections, a subcutaneous cuff constructed of a biodegradable collagen matrix impregnated with bactericidal silver was developed.

Enhanced exercise noradrenaline concentrations during propranolol treatment: a limiting factor in cardiac beta-adrenoceptor blockade.

Treatment with beta-adrenoceptor blocking drugs may result in augmented plasma concentrations of noradrenaline during exercise. The effect of propranolol on exercise heart rate and its relationship to plasma concentrations of propranolol and noradrenaline were examined in 10 hospitalized volunteers following treatment with propranolol, in doses of 80 mg and 320 mg daily. Responses to submaximal treadmill exercise during propranolol treatment and following discontinuation of the higher dose were compared to pre-drug and post drug placebo values.

Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction.

A prospective study to determine prognostic factors for risk stratification in 867 patients surviving the coronary care unit phase of acute myocardial infarction (AMI) is reported. During a 48-month follow-up, 144 patients (17%) died. The deaths were examined for the chronology, cause, mechanism, location and presence of myocardial ischemia in the terminal event.

Automatic external defibrillators: importance of field testing to evaluate performance.

A new automatic external defibrillator was tested first against a tape-recorded data base of rhythms and then during use by first-responding fire fighters in a tiered emergency system. The sensitivity for correctly classifying ventricular fibrillation and ventricular tachycardia was substantially less during clinical testing in 298 patients than would have been predicted from preclinical results: 52% of ventricular fibrillation analyses in patients were correctly classified versus 88% of episodes in the data base, and 22 versus 86%, respectively, for ventricular tachycardia (p less than 0.001).

Treatment of the murine lymphoma A31 with intravenous, sterilized, 114mIn-loaded A31 cells.

The effect on a mouse B-cell lymphoma (A31) of intravenously (i.v.) injected, sterilized, A31 lymphoma cells loaded with [114mIn]oxine was examined.

Reinforcing CPR skills without mannequin practice.

We studied the effectiveness of two refresher methods on skills that did not involve mannequin practice. Sixty-seven Seattle subjects trained one year earlier were pretested and randomly assigned to one of two treatments that covered the technique of one-rescuer CPR: reading a three-page review (n = 33); or viewing a 15-minute videotape (n = 34). Subjects were tested on a recording mannequin immediately after the refresher.

The central venous anatomy in infants.

A study of 21 consecutive autopsy specimens of infants less than one year of age and weighing less than 6 kilograms was performed to determine the topographic anatomy and regional relationships of the central venous anatomy. This anatomy was compared with 14 additional autopsies performed upon older children. There was no significant difference in diameter between the internal jugular and subclavian venous system, on either the right or left side.

CPR training for patients' families: do physicians recommend it?

All Seattle-area cardiologists and 25 per cent of selected other physicians were queried by mail to determine whether they recommended CPR (cardiopulmonary resuscitation) training for families of their patients. Two-thirds reported that they advocated training for some patients' families, but only 52 per cent of cardiologists and 37 per cent of the others did so for families of at least half of the patients considered at risk. Physicians who had performed out-of-hospital CPR or had received advanced or recent training were more likely to recommend instruction.

Radioimmunotherapy of malignancy using antibody targeted radionuclides.

Antibodies directed against tumour associated antigens provide a means for delivering preferentially cytotoxic radionuclides to the cells of primary and secondary tumours. The factors that influence the effectiveness of the radiation in the tumour compared with its effect on the radiosensitive normal tissues include the specificity of the antibody, the distribution of targeted energy within the tumour and the host's response to the injected foreign antibody. Recently some encouraging results from clinical trials of radioimmunotherapy have been reported in the literature.

Characterisation of a new murine B cell lymphoma.

The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour.

Considerations for improving survival from out-of-hospital cardiac arrest.

Since the implementation of a paramedic system in Seattle, yearly survival rates from out-of-hospital cardiac arrest due to ventricular fibrillation have averaged 25% without any significant increase over the years. Outcome for cardiac arrest associated with other rhythms has been poor: when asystole was the first rhythm recorded, only 1% of patients survived; when electromechanical dissociation was initially present, only 6% survived. For cases of electromechanical dissociation, neither the type of rhythm nor the rate appear to influence outcome.

Neurologic outcome and blood glucose levels during out-of-hospital cardiopulmonary resuscitation.

We examined the interrelations of outcome, time elapsed during cardiopulmonary resuscitation (CPR), and blood glucose levels drawn from 83 patients with out-of-hospital cardiac arrest. Levels rose significantly during CPR. Although slope and intercept of regression lines differed for those dying in the field and those admitted, regression lines were similar for those who awoke and never awoke after admission.

Cardiac arrest treated with a new automatic external defibrillator by out-of-hospital first responders.

Two hundred sixty patients in cardiac arrest were treated with an automatic external defibrillator by first-responding firefighters before arrival of paramedics. On average, first responders arrived 5 minutes before paramedics. Of 118 patients with ventricular fibrillation, 91 (77%) were administered shocks, 21 (23%) of whom had return of pulse and blood pressure by the time paramedics arrived.