Fibrinolytic therapy in subacute bacterial endocarditis: an experimental study.

The effect of adding fibrinolytic to penicillin therapy in experimentally induced streptococcal bacterial endocarditis has been studied in the rabbit. In 9 day old infected lesions, the vegetations could be substantially reduced in size after a 3 day course of intravenous streptokinase. Quantitative microbiological techniques demonstrated that the addition of streptokinase to standard intravenous penicillin treatment led to more rapid sterilisation of the vegetations. Embolism to lungs and kidneys was assessed in treated and untreated rabbits. Penicillin reduced the rate of embolism but the addition of streptokinase reversed this effect and gave values similar to those recorded in untreated animals.

The estimation of neuronal population density by a robust distance method.

A new "nearest-neighbour" or "distance" method of estimating neurone population density is introduced. The method was originally developed for ecological studies but can be imported into histology without significant modification; changes in population density can be estimated by inverting the measure of area per unit cell (the so-called mean area). Its advantages include tests of randomness for the spatial distribution of the cells at issue and a robustness which can tolerate some departure from a random distribution pattern. To illustrate how the method is applied estimates of neurone density, in terms of "mean area" per cell-point, are made on a montage tracing of the human cerebellar dentate nucleus.

A reappraisal of the stathmokinetic technique. II. Metaphase degeneration and its correction.

The rate at which proliferating cells enter mitosis is an important cytokinetic measure. It is estimated by the metaphase arrest (or stathmokinetic) technique. This technique depends on the persistence of arrested metaphases in the tissue in question. But arrested metaphases do not, in fact, persist for long; some estimates of the rate at which cells are entering mitosis, based on a count of metaphases, are therefore underestimates. This paper presents a mathematical analysis of this phenomenon and a method of calculating the initial metaphase index from the depleted index at any given time.

Cell population kinetic profile of the mouse thymus, and the changes induced by prednisolone.

The cell population kinetic parameters of the thymus in BALB/c mice have been estimated using stathmokinetic and [3H]TdR techniques in both control animals and animals treated with prednisolone. FLM data were analysed by computer using the Gilbert program. The study showed that prednisolone had an inhibitory effect mainly in the DNA synthesis phase and in G1. Stathmokinetic data also showed a decrease in the cell birth rate and an increase in the apparent cell cycle time (or potential doubling time) after treatment. The labelling index, the mitotic index and the growth fraction were also decreased. The study also shows a good agreement between the data obtained by stathmokinetic and [3H]TdR techniques.

The effects of dexamethasone on the cell kinetics of a murine malignant lymphoma.

The effects of dexamethasone on the cell kinetics of a rapidly growing syngeneic B cell malignant lymphoma in Balb/c mice have been studied. Growth curves, stathmokinetic studies and frequency of labelled mitoses (FLM) experiments were performed in groups of dexamethasone treated and control animals. These studies showed that tumour growth was arrested after 8 days treatment at which time the tumour weights were approximately half those of control animals. Dexamethasone increased the duration of the cell cycle with a particular increase in the duration of DNA synthesis. The results indicated that the effect on tumour growth could be attributed to a reduction in the growth fraction.

Cytokinetic changes in the thymus of tumour-bearing and of dexamethasone-treated mice.

Changes in the cell population kinetics of the Balb/c mouse thymus were studied (a) during the growth of a syngeneic transplantable sarcoma and (b) following intraperitoneal injection of dexamethasone. The weight of the thymus fell briefly after tumour transplantation, then recovered with overshoot and eventually declined profoundly. After dexamethasone injection the weight of the thymus fell to roughly one-third of its normal value in 36 hr. Similar cytokinetic changes were observed in both sets of experiments; thymic wasting was accompanied by a small increase in thymocyte cell cycle time, a prolongation of the S-phase of the cycle, a marked decrease in the thymocyte cell production rate and a marked reduction in the growth fraction of the thymocyte population in the superficial cortex. It is suggested that thymic atrophy in tumour bearing animals may be a stress phenomenon.

Assessment of inherent fluctuations of mitotic and labelling indices of human tumours.

A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours.

Sudden and unexpected deaths in infants: histology and virology.

The histological appearance of lungs of children whose death had been sudden and unexpected has been studied in relation with the viruses found at necropsy. Fifty-one children were investigated and in 33 the lungs had the histological appearance widely accepted as characteristic of the condition previously termed "cot death." Sixteen had the histological appearance of lymphocytic bronchiolitis, and it was from this group only that viruses were isolated. The viruses isolated were those associated with respiratory infections. Two patients showed the histological appearance of bacterial bronchopneumonia. Viruses are probably responsible for a substantial proportion of unexpected sudden deaths in infancy.