Feasibility of Dose-escalated Hypofractionated Chemoradiation in Human Papilloma Virus-negative or Smoking-associated Oropharyngeal Cancer.

AIMS: Oropharyngeal squamous cell carcinoma (OPSCC) can be divided into favourable and poor prognostic groups by association with human papilloma virus (HPV) and smoking. This study prospectively investigated a dose-intensified schedule in poor/intermediate prognosis OPSCC. MATERIALS AND METHODS: Patients with p16/HPV-negative or p16-positive N2b OPSCC with a greater than 10 pack-year smoking history were eligible. Patients were planned to receive 64 Gy in 25 fractions with cisplatin. The primary end point was absence of grade 3 mucositis at 3 months. RESULTS: Fifteen patients were recruited over 14 months. All patients completed a minimum of 2 years of follow-up. All patients completed full-dose radiotherapy within a median treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at 3 months. There was one grade 4 toxicity event due to cisplatin (hypokalaemia). Complete response rates at 3 months were 100% and 93% for local disease and lymph nodes, respectively. One patient developed metastatic disease and subsequently died. Overall survival at 2 years was 93% (95% confidence interval 61-99%). CONCLUSIONS: The schedule of 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor and intermediate prognosis OPSCC.

A hybrid computational model for the effects of maspin on cancer cell dynamics.

Cancer metastasis is a complex multistep process which allows cancer cells to establish new tumours in distant organs. The process of metastasis involves cell migration and invasion; it is what makes cancer a fatal disease. The efficiency of most cancer treatments depends on metastasis suppression. Maspin is a type II tumour metastasis suppressor which has multiple cellular effects. It has been described as a key regulatory protein in both the intracellular and extracellular environments. Maspin has been shown to reduce cell migration, invasion, proliferation and angiogenesis, and increase apoptosis and cell-cell adhesion in in vitro and in vivo experiments. The clinical data regarding the predictive effects of maspin expression are variable. To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not been clearly defined. The diversity of the effects of maspin motivated us to develop an intelligent model to investigate its effects on cellular proliferation and migration. This paper reports a hybrid model of solid tumour growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the cancer cell. A feed-forward neural network was used to model the behaviours (proliferation, quiescence, apoptosis and/or movement) of each cell, which has been suggested as a suitable model of cell signalling pathways. Results show that maspin reduces migration by 10-40%, confirmed by published in vitro data. The model also shows a reduction in cell proliferation by 20-30% in the presence of maspin. So far, this is the first attempt to model the effect of maspin in a computational model to verify in vitro data. This will provide new insights into the tumour suppressive properties of maspin and inform the development of novel cancer therapies.

Vitamin A status does not influence neopterin production during illness or health in South African children.

Excessive interferon-gamma (IFN-gamma) production appears to be a primary immunological lesion in vitamin A-deficient experimental animals but comparable data from humans is lacking. We investigated IFN-gamma production in South African children by measurement of urinary excretion of neopterin, a product of IFN-gamma-activated monocytes or macrophages. Preschool children were examined during an acute inflammatory illness resulting from accidental ingestion of kerosene and they and a neighbourhood control child were examined 3 months later when well. Vitamin A status was assessed by the modified relative dose response (MRDR) test at 3 months and serum retinol and acute phase proteins were measured at both time points. Urinary neopterin was measured for forty cases in hospital, forty-six cases after recovery, and forty-one controls. Significantly increased neopterin excretion was seen following kerosene ingestion and in association with raised serum acute phase protein concentrations. There was no relationship between neopterin excretion at either time point and vitamin A status as assessed by MRDR test. Urinary neopterin was negatively correlated with serum retinol but no significant relationship was observed when acute phase protein concentrations were included in a multiple regression, suggesting the correlation was secondary to illness-induced changes in serum retinol. The results indicate that, contrary to what is observed in rodents under experimental conditions, poor vitamin A status is not associated with altered regulation of IFN-gamma production in children.

Urban community health workers: selection, training, practice and outcomes.

The role, desirability and success of community health workers is debated. Conflicting reports have highlighted important concerns and provided guidelines. Particular issues identified are the necessity for both community and health professional input to determine needs and to ensure an acceptable selection process, training, support and accountability. Such steps were followed in the Greater Soweto Maternal Child Project. These are described together with the results achieved. Eight trained Soweto community health workers centered at Chiawelo Clinic and providing home based and neighbourhood health care undertake supervised Tuberculosis treatment, tracing of immunisation defaulters, and health education based on GOBI FFF (Grant JP, UNICEF:1985;94) and "Facts for Life" (UNICEF 1989-1993). They form a link between the community and government health care services and also other available resources. Over a period of 26 months, working from their own homes, they provided 14,254 health related services and in addition undertook 14,501 neighbourhood home visits. They were responsible for 8,710 referrals to the clinic or other relevant agencies for assistance. Incremental training has included HIV/AIDS counselling, advice on family planning with regular report back sessions and discussions. Participatory management involves all major role players. The community health workers have the approval and support of the Local Soweto Health Authority, the Civic Association and the communities they serve. On completion of the project, all were redeployed into local health service posts where it is intended that they form the nucleus of an expanding service. Delegation of selected tasks allows for cost effective functioning of more highly trained staff, an improved service and better use of available resources.

Prediction of illness severity and outcome of children symptomatic following kerosene ingestion.

Kerosene pneumonitis is usually self-limiting and secondary infection is rare. Long-term studies in developed countries have produced conflicting results about complications. The position in developing countries, where children are exposed to adverse environmental and nutritional factors, is unknown. The aim of the present work was to determine whether there is an increase in respiratory or other illnesses following kerosene pneumonitis and whether these changes could be related to the severity of the initial lung damage. Fifty-seven children with clinical signs of pneumonitis were examined on admission and after overnight observation. Clinical signs were assessed for their usefulness for predicting severity. Cases and matched neighbourhood controls were seen every 2 weeks for 3 months. The time to predict most reliably the severity of short-term ill effects was 12-24 hours after the initial insult. There was no significant difference in respiratory symptoms during the 3-month follow-up in cases compared with controls. However, mild diarrhoea and fever were reported significantly more often in cases than in controls. Morbidity after clinical recovery was not shown to be a problem, irrespective of the severity of the acute event.

Toxic damage to the respiratory epithelium induces acute phase changes in vitamin A metabolism without depleting retinol stores of South African children.

Whereas there is much information concerning the effects of vitamin A status on response to infectious challenge, the effects of infection or trauma on vitamin A metabolism and status are less well documented. These relationships need to be understood to optimize clinical and public health programs to improve vitamin A status and health of children in less-developed countries. We measured acute changes in retinol and retinol-binding protein in 57 young South African children hospitalized following respiratory epithelial damage resulting from accidental ingestion of kerosene. In addition, vitamin A status, as measured by the modified relative dose response test, of these children 3 mo later was compared with that of neighborhood control children to determine whether their illness had depleted retinol stores. Plasma retinol was already significantly below control levels when children were admitted [geometric mean (95% CI): 0.57 micromol/L (0.48-0.67) compared with 1.15 micromol/L (1.02-1.30) for controls] and decreased further the following morning [0.38 micromol/L (0.31-0.46)]. Significant differences in retinol-binding protein were not detected until the next morning [5.99 mg/L (4.70-7.63) compared with 14.0 mg/L (11.8-16.6) for controls] and were not as large as the relative differences in retinol. This dissociation between changes in retinol and its binding protein suggests that there may be increased retinol uptake by certain tissues during the acute phase response. The proportion of case children (37/46, 80%) with inadequate liver retinol stores 3 mo after the illness was slightly, but not significantly (chi2 = 2.16, P = 0.14), greater than the proportion of control children (28/42, 67%). Acute respiratory illness therefore did not further deplete retinol stores in this population in which stores were already frequently inadequate.

Cavitation damage of pyrolytic carbon in mechanical heart valves.

A summary of the observations of cavitation-related damage is presented for over a hundred mechanical heart valves (MHV) containing pyrolytic carbon components. Valves were obtained from several types of simulators, animal studies and clinical explantations, and were primarily of the bileaflet type. Damage on these valves was documented as to location, type, and severity. This report focuses on the damage location where cavitation bubbles have been observed in vitro. Pitting and microcracking are the forms of damage observed that can be associated with cavitation. The pitting is primarily of a focal nature and is thought to be due to cavitation bubble collapse or, possibly, initiation. Certain features of the deposited material appear to be important relative to cavitation damage resistance and the so-called cavitation threshold of a MHV. A highly polished surface with few micropores provides few nucleation sites for cavitation bubbles and will better withstand cavitation forces. Attributing certain observations of in vivo damage to cavitation is done by inference from; 1. the similarity of the damage features observed on explants to those produced by cavitation in vitro, and 2. the identity of the location of this damage with the location of cavitation as observed by high speed video (HSV). In addition, confirmation was obtained in a number of instances by in vitro observation of cavitation coinciding with a specific damage location on the same explanted MHV. In most of the fractures, a focal pit was usually present on the fracture line at or near the fracture origin, indicating pitting as a primary damage mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth to ten: child health in South Africa in the 1990s. Rationale and methods of a birth cohort study.

Birth to Ten is a longitudinal birth cohort study which began in April 1990 in the Johannesburg/Soweto area of Transvaal, South Africa. In this paper, the reason for the initiation of the study and its location in the current sociopolitical context is discussed. The health status of South Africa children in terms of infant mortality, morbidity (notifiable diseases) and nutritional status is described and mention is made of measures of psychological health and the importance of environmental pollution on health. The existing health service infrastructure in the study area is described and the fragmentation of health services between races, between preventive and curative services and on a geographical basis is highlighted. The study objectives, design, population, inclusion and exclusion criteria, methods of measurement and logistics are described.

'Birth to Ten'--pilot studies to test the feasibility of a birth cohort study investigating the effects of urbanisation in South Africa.

'Birth to Ten' is a birth cohort study currently being conducted in the Johannesburg-Soweto area. This paper describes the various pilot studies that were undertaken to investigate the feasibility of a cohort study in an urban area. These studies were designed to determine the monthly birth rate, the timing, frequency and duration of maternal antenatal visits, the timing and frequency of visits to well-baby clinics and the accuracy and reliability of routinely collected growth data. In addition, a birth data collection form was tested to ascertain the appropriateness of its use in clinics within the study area.

Televised paediatric consultations: a student evaluation of a multipurpose learning strategy.

Since 1984, each student in the sixth-year paediatric rotation in the Department of Paediatrics and Child Health at the University of the Witwatersrand has been videotaped while undertaking a comprehensive paediatric primary care consultation. Video replay of the consultation by each individual student was evaluated by the student together with medical and social work tutors. This incorporated psychosocial aspects, communication skills, doctor-mother-child interactions, as well as essential medical content, clinical examination techniques, and management strategies. The student was expected to provide comprehensive health care, viz. dealing with the presenting health problems, identifying any possible hidden agenda, giving due attention to nutrition, immunization, development, optimal use of available records, health surveillance and appropriate education. This teaching programme was introduced in 1984. In 1988, 68 consecutive final-year medical students completed an anonymous Likert-type evaluation form scoring their perceived learning. They affirmed that the use of television in medical education provides a unique multipurpose learning strategy and in particular enhances awareness of self and of patient/family needs. The time, cost and effort invested in this programme are considered justified.

Measles, mumps and rubella immunization at nine months in a developing country.

The antibody responses and reactogenicity of a measles, mumps and rubella vaccine in 9-month-old and 15-month-old black children in South Africa were compared. The antibody response to the measles component was marginally better in the older group, but no differences were observed in the response to the mumps and rubella components. Reactogenicity was similar in the two age groups. Therefore it is possible that a trivalent measles, mumps and rubella vaccine can safely and effectively replace routine measles immunization at 9 months of age in this population. Whether routine immunization policy should incorporate such a vaccine depends on the extent of acceptance of measles vaccination. In urban populations of developing countries with high rates of measles immunization, routine vaccination at 9 months might interrupt circulating wild type rubella and provide sufficient herd immunity to protect susceptible women of childbearing age. It also should decrease significantly the complications associated with wild type mumps infection. The replacement of measles vaccine by a trivalent vaccine may be very cost-effective.

Infant diarrhoea in Soweto--how much oral rehydration therapy?

In Soweto, infant morbidity and mortality from gastro-enteritis have markedly declined. Nevertheless, there were 1514 admissions to the Baragwanath Infant Gastro-enteritis Unit in a 12-month period (1985/6). Oral rehydration therapy (ORT) could be implemented with advantage not only as a life-saving strategy but for self-help management of milder diarrhoea. Surveys conducted in Soweto and at Baragwanath showed that 84 (22%) of 382 mothers/minders of children knew formulas for acceptable salt-and-sugar oral hydration solutions (OHS), although 203 (53%) claimed to have knowledge of ORT. One hundred and ten interviewees (29%) were aware of the desirability of giving extra fluid to a child with diarrhoea. A need exists for health educators to explain and ensure understanding of the basic concept of adequate fluid replacement that is fundamental to ORT. This important message may have been overshadowed by emphasis on choice of containers and different formulas with consequent confusion.

Breast feeding practices of nurses at Baragwanath, Coronation and Johannesburg hospitals.

PIP: In South Africa, researchers studied breast feeding practices among nursing personnel who took maternity leave between January 1, 1985 - December 31, 1986 at 3 Johannesburg hospitals. These women completed the questionnaires in July 1987 so the study results would be available for the 1st South African National Breast Feeding week (October 31- November 7, 1987). 68% of the infants were breast fed for 12 weeks. Only 6% were never breast fed as compared to 17% of their older siblings. 60% of the nurses at Baragwanath Hospital, 11% at Coronation Hospital, and 14% at Johannesburg Hospital continued to breast feed after returning to work. While breast feeding upon return to work was high among all nurse categories, nursing assistants were more likely to do so (75% vs. 66% for sisters and 68% for staff nurses). Breast feeding problems ranged from breast problems to failed or inadequate lactation. 100% of the nursing personnel at Coronation reported failed or inadequate lactation as a problem. Even though the study was not racially based, results demonstrated superior breast feeding practices among the nursing personnel at Baragwanath who are black. The average number of weeks taken for maternity leave for all nursing personnel stood at 12 - 13 weeks. Unpaid leave averaged 32-33 weeks. Unpaid leave averaged 32-33 weeks. 56% of all nursing personnel depended on relatives to care for their infants. This was especially true for Baragwanath nursing personnel (61%). 77% of the respondents expressed a need for day care, 35% of whom preferred a day care facility at the hospital. The study demonstrated strong breast feeding practices among nurses who are good models for the community and these actions serve to promote breast feeding.^ieng

Whither school health services for lower primary schoolchildren in Soweto?

Over 1,000 clinical examinations and screening procedures in Soweto lower primary schoolchildren revealed few significant health problems which had not previously been identified. Information from parents and teachers was of limited value. The study revealed that only a small percentage of children referred for further medical attention attended for investigation or treatment as advised. Most of the health problems found could well have been managed at a school-based primary care level. It would thus be desirable to modify and extend the role and functions of the school nurse. However, the effectiveness of so doing would depend on adequate training, the availability of personnel and the organisational structure of health care services.