Prevalence of Heroin Misuse in Oxford City

It is generally believed that the prevalence of drug misuse, and especially of opioid misuse, is increasing. The prevalence of heroin misuse in Oxford City was estimated accurately in 1969 using a detailed multi-agency enumeration method, and it was therefore possible to repeat this procedure to obtain an estimate of the current prevalence, and hence a longitudinal view of the problem. In one year 246 heroin users were identified, giving an overall 12-month period prevalence rate of 3.7 per thousand in the age range 15–49 years. This finding suggests that the prevalence of heroin misuse in Oxford City is little different from that of 1969.     

Congenital Factor VII Deficiency with Normal Stuart Activity: Clinical, Genetic and Experimental Observations

The case of a four year old white girl with a bleeding tendency characterized by the spontaneous occurrence of petechiae, ecchymoses andhemarthroses is presented. Laboratory studies indicate a deficiency of factorVII, with normal levels of all other clotting components, and a vascular deficiency possibly related to frequent upper respiratory infection.

Serum from the patient and from four close relatives having reduced levelsof factor VII is shown to correct the abnormal thromboplastin generation ofStuart factor-deficient serum. The rate of conversion of prothrombin intothrombin is markedly delayed in the patient’s plasma but essentially normalin that of other family members. The patient’s prothrombin conversion iscorrected by the addition of normal or Stuart-deficient plasma. The partialthromboplastin time of the patient is somewhat prolonged.

It is concluded that factor VII deficiency is inherited in this family as anincompletely recessive autosomal characteristic. The penetrance of the deficiency allele in the heterozygous individual appears to be variable. Analysesof the distributions of clotting factor levels in the family and in samplesfrom the normal population indicate that an individual may vary greatly inhis clotting factor levels, the average variation being nearly as great as thevariation among individuals. The magnitude of the variation among siblingssuggests that the penetrance of the factor VII deficiency allele is affected byextrinsic factors and that the observed population variation does not resultfrom the occurrence of multiple alleles. It is suggested that sex may be afactor determining clotting factor levels.

The bleeding of the patient is controlled by transfusion of plasma and byinjection of a plasma preparation called ACC-76 (Behringwerke, Germany),the latter followed by a transient elevation of blood factor VII.

Submitted on March 11, 1959 Accepted on May 18, 1959     

Characterization of an animal model of hepatic metastasis

The experimental study of possible therapies for control of the growth of liver metastases requires the availability of a model which is technically feasible and appears to exhibit growth characteristics similar to human tumours. We report on the development of an intrasplenic injection model of liver metastases, and describe the histology, growth pattern and blood flow demonstrated by light microscopy, stereology and laser Doppler flowmetry. The hepatic metastases were induced in mice by intrasplenic injection of dimethylhydrazine (DMH) induced primary colonic carcinoma cells (10⁶ cells in 1 mL). The growth and development of metastases was studied over a period of 3 weeks at predetermined time points. Tumour cells were visible in the hepatic sinusoids by day 7 by light microscopy. Macroscopically visible tumours with a diameter of 0.18 ± 0.02 cm (mean ± s.d.) were seen by day 10. By this time the tumours had derived a blood supply from the hepatic sinusoids adjacent to the tumour periphery. With further vascularization the tumours reached a diameter of 0.96 ± 0.50 cm by day 22. Metastatic growth was quantitated by stereological analysis of tumour volume in relation to non-diseased hepatic tissue. Normal mouse liver had a mean volume of 1.13 ± 0.14 cm³. Tumour growth occurred in three phases. During the initial slow phase the volume of metastases increased from 0.03 ± 0.02 cm³ at day 10 to 0.22 ± 0.24 cm³ by day 16. Rapid tumour growth, occurring over the next 3 days, constituted the intermediate phase with metastatic volume reaching 1.21 ± 0.74 cm³ by day 19 (P= 0.0003 compared with day 16). This growth was followed by a plateau phase when the metastatic volume was 1.40 ± 0.55 cm³ at day 22. The volume of total liver and of tumour necrosis followed a similar growth pattern. A necrotic tumour volume of 0.004 ± 0.006 cm³ first seen on day 10 increased to 0.05 ± 0.06 cm³ by day 16, and to 0.25 ± 0.20 cm³ by day 22 (P=0.0022 compared with day 16). The blood flow in metastases measured by laser Doppler flowmetry was lower compared to the non-diseased liver. Tumour blood flow, expressed as a percentage of normal liver blood flow, was 63.31 ± 26.28% at day 10 and diminished to 27.91 ± 8.99% by day 22, with an increase in tumour size and age. The decrease in flow was significant between days 13 and 16 (P= 0.0015). This intrasplenic mouse model of metastases is reproducible and should prove useful in the study of treatment of hepatic metastases.