Nonlinear pharmacokinetics of tissue-type plasminogen activator in three animal species: a comparison of mathematical models.

A recent study presented plasma concentrations of tissue-type plasminogen activator in three different animal species and at several different dose levels. A three-compartment mammillary model with capacity-limited elimination (of Michaelis-Menten form) was postulated to describe the data. In the present study, several alternative model structures are examined with the view of determining whether better fits can be obtained, whether linear models are significantly worse than nonlinear models, and whether all three compartments are really necessary.

CODE: a deconvolution program implementing a regularization method of deconvolution constrained to non-negative values. Description and pilot evaluation.

A regularization method of deconvolution constrained to non-negative values is described. The method gives smooth estimates of the input function whilst providing a feasible fit (in terms of least squares) to measurements. A description of the program CODE (constrained deconvolution) which implements the method is given. A new methodology for a pilot evaluation of deconvolution programs is also proposed. The methodology is based on synthetic data. It employs a variety of shapes of the input function, low (1%) and high (15%) values of the measurement error, and incorporates primary (accuracy) and secondary (bias) performance measures. The performance of CODE is evaluated and it is suggested that CODE provides estimates of the input function with acceptable accuracy.

A comparison of six deconvolution techniques.

We present results for the comparison of six deconvolution techniques. The methods we consider are based on Fourier transforms, system identification, constrained optimization, the use of cubic spline basis functions, maximum entropy, and a genetic algorithm. We compare the performance of these techniques by applying them to simulated noisy data, in order to extract an input function when the unit impulse response is known. The simulated data are generated by convolving the known impulse response with each of five different input functions, and then adding noise of constant coefficient of variation. Each algorithm was tested on 500 data sets, and we define error measures in order to compare the performance of the different methods.

Multifocal inflammatory leukoencephalopathy developing in a patient receiving 5-fluorouracil and levamisole.

A single case of multifocal inflammatory leukoencephalopathy, which developed during a course of adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is reported. Clinical features developed slowly and were not dramatic; this condition may therefore frequently be missed.

Factors in the home environment which influence sexual knowledge and sexual activity among pre-adolescents in Kingston and St. Andrew, Jamaica - implications for prevention of HIV infection - abstract

Children and adolescents are an important target group for primary prevention of human immunodeficiency virus (HIV) infection, but information about their sexual knowledge and behaviour is sketchy. We therefore undertook a study of 518 school children, aged 8 to 12 years, in 15 schools, using a multi-stage sampling method. We used a structured questionnaire to enquire about living arrangements, relationships with parents and guardians, knowledge about sex and sexually transmitted diseases, and sexual experiences. We analysed correlations between the variables. There was a higher level of reported sexual activity among children when: (a) a sibling (instead of the other parent or another adult) was the substitute care-giver while the parent(s) travelled away from home (relative risk (RR) = 3.98; p<0.001); (b) the children were not occupied with home-work or household chores after school (RR=2.0, p=0.01); (c) they shared sleeping facilities instead of sleeping in their own bed (RR=1.86, p=0.01); (d) they could visit neighbours or friends without requiring parents' or guardians' permission (RR = 2.40, 2.75, respectively; p=<0.001, 0.0001, respectively). Travelling patterns of parents per se did not influence level of sexual activity of their children (RR = 0.83 (95 percent confidence interval 0.51 - 1.75, p = 0.45). One hundred and fifty-seven children (31 percent) said that they had first learnt about sex through television, while 62 (12 percent) had learnt first from a parent. Four hundred and thirty-nine children (86 percent) had heard about AIDs from some source, although the information was not always clear or accurate in their minds. Two hundred and eight-five children (56 percent) said they would like their parents to teach them about sex, while 220 (43 percent) suggested that parents teach them about Sexually Transmitted Diseases. This study is part of an on-going project aimed at designing an educational intervention programme for parents and children (AU)

A comparison of doxorubicin, epirubicin and mitozantrone as single agents in advanced breast carcinoma.

Between July 1985 and December 1987, 87 patients with advanced breast carcinoma were randomized to receive single agent doxorubicin (70 mg/m2), epirubicin (70 mg/m2) or mitozantrone (14 mg/m2) at 3-weekly intervals. The patients had received no previous chemotherapy for their advanced disease but 91% had received prior hormonal therapy. The response rates were 36% with doxorubicin, 32% with epirubicin and 26% with mitozantrone, but these differences did not reach statistical significance. The median survival of all patients was 8.3 months. There was no significant difference in response rates or survival according to menopausal status. The toxicities of the three agents are compared. Nausea, vomiting and alopecia were more severe in patients treated with doxorubicin or epirubicin than those treated with mitozantrone. Myelosuppression and infective episodes occurred more frequently with mitozantrone. Two cardiac complications were reported. This study shows that the toxicity and low efficacy of all three agents limit their use as single agents in advanced breast carcinoma. The role of single agent chemotherapy and the relative toxicities of these drugs are discussed.

Coping and the outcome of stoma surgery.

A prospective 12 month study of 106 subjects who underwent stoma surgery was conducted and has been described previously. Coping responses to the underlying diagnosis and to the stoma itself were assessed at 3 and 12 months post operatively and are related to the outcome 3 years after the operation. Difficulty coping with the stoma itself was a greater determinant of later psychiatric disturbance than difficulty in coping with the illness. Physical outcome, in those with colorectal carcinoma, was influenced by coping strategies only in the males, denial over diagnosis was significantly associated with poor outcome whereas fighting spirit over the stoma was associated with a good outcome.

Psychological effects of stomas--I. Psychosocial morbidity one year after surgery.

Sixty eight subjects who had undergone stoma surgery 12 months previously were assessed as to their psychiatric and social outcome. They had been previously also assessed at the 3rd month postoperatively. The majority had a diagnosis of bowel cancer (38) and smaller numbers had inflammatory bowel disease (15) or diverticular disease (15). 22% of the subjects had moderate or severe psychiatric symptoms and most of these had also shown similar disturbance at the 3 month assessment, indicating that the condition was longstanding. There was no significant difference in outcome between the diagnostic groups. The results also showed that ability to perform housework, leisure and sexual activities was affected in a number of subjects.

Psychological effects of stomas--II. Factors influencing outcome.

Sixteen patients with a moderate or severe anxiety and/or depression one year after stoma surgery were compared with 52 patients who had made a good psychiatric adjustment. Factors that were associated with an increased risk of psychiatric morbidity included a previous psychiatric history, postoperative physical symptoms and complications, inadequate advice and personality traits of neuroticism, anxiety and obsessionality.

Tracheal carcinoma following short term tracheostomy in childhood (a case report).

Carcinoma of the trachea is rare in comparison to other neoplasms of the respiratory tract. Cigarette smoking has been implicated in its aetiology, but unlike carcinoma of the bronchus and lung, the incidence of tracheal carcinoma has not risen with tobacco consumption (Hajdu et al., 1970; Ranke et al., 1962). It seems, then, that there is some mechanism or mechanisms which render the trachea especially resistant to malignant change.

Psychosocial morbidity in the first three months following stoma surgery.

One hundred and six consecutive subjects were seen in hospital a few days after undergoing surgery for bowel disease that necessitated the formation of a stoma. They consisted of patients with cancer (74), colitis (17) and diverticular disease (15). At this initial assessment details of psychological and social functioning were obtained for the preceding three months before operation. At 3 months post-operatively the subjects were interviewed in their own homes, 87 subjects were available (12 died, 7 refused) and again psychological and social assessments were made. Seventeen per cent of males and 19% of females had moderate or severe psychiatric disturbance and there was also a significant number of patients with various social disturbances. Physical diagnosis did not significantly affect psychiatric outcome. There was, however, high pre-operative psychiatric disturbance and the relevance of this in assessing post-operative symptoms is discussed.

The role of radiotherapy in the treatment of soft tissue sarcoma: a retrospective study 1958--73.

Survival and local control data are presented for a series of 109 cases of soft tissue sarcoma treated 1958--73. A five-year minimum follow-up period is available. The two-year and five-year survival rates for the complete series are respectively 80 and 68%. In a comparison of survival results for different histological subgroups we found a 94% two-year survival for liposarcomas compared with 80% for fibrosarcomas and 74% for synovial sarcomas; and five-year survivals of 73, 68 and 51% respectively. Sixty-two per cent of the series achieved local control of the disease after initial treatment, and this figure increased to 83% after further treatment. Eighty-six per cent of tumours of the extremities (66/77) were controlled locally without amputation. Of those in the complete series whose disease recurred, either locally or distantly, 50% experienced this recurrence within one year of initial treatment. In only 7% did the recurrence occur more than five years after initial treatment. These results are encouraging and we conclude that they justify an initial treatment policy of conservative surgery combined with radical radiotherapy.