Choroid thickness profile in patients with lupus nephritis.

BACKGROUND: Choroidopathy is a rare manifestation of systemic lupus erythematosus (SLE). This entity is associated with active phases of severe SLE and it is frequently accompanied by acute kidney failure, central nervous system involvement and coagulopathy. PURPOSE: To evaluate the choroid thickness of patients with lupus nephritis (LN) without choroidopathy, and to compare this with that of age-matched SLE patients without LN and healthy control subjects. STUDY DESIGN: Cross-sectional case control study. MATERIAL AND METHODS: Fifteen women with LN in remission phase (study group), 15 women with SLE in remission without LN (SLE control group), and 15 healthy women (healthy control group), without ocular diseases or significant refractive error, were recruited. Full ophthalmological examination and a macular optical coherence tomography in enhanced depth imaging mode were performed. The choroid thickness was measured at nine macular points and six lines of mean choroidal thickness were determined. A comparative analysis between the three groups was performed using the one-way ANOVA test and the paired t-test. The choroid thickness of patients under corticotherapy was also compared to that of patients without corticotherapy. Additionally, the correlation between choroid thickness and disease duration was evaluated using the Pearson analysis. RESULTS: The mean macular choroidal thickness was 295.73 ± 67.62 µm in the study group, 233.34 ± 41.01 µm in the SLE control group, and 240.98 ± 37.93 µm in the control group ( p = 0.00006 and p = 0.0003, respectively). Additionally, the choroid thickness was significantly thicker than in the SLE and healthy control groups at the foveal ( p = 0.004 and p < 0.000), nasal ( p < 0.000 and p = 0.001), superior ( p = 0.002 and p < 0.000) and inferior ( p < 0.000 and p = 0.001) mean lines. The choroidal thickness in this group was not associated with the duration of the disease. The subgroup of patients with LN under corticotherapy did not reveal a significantly different choroidal thickness. CONCLUSION: This study suggests a relationship between LN and choroidal changes, which may represent an increased risk for choroidopathy in these patients. Choroid thickening was not related with the duration of the disease. This thickening may be correlated with histopathological changes similar to those occurring in kidney glomeruli.

Dosimetric considerations in the treatment of inoperable endometrial carcinoma by a high dose rate afterloading packing technique.

A series of 23 patients with early adenocarcinoma of the endometrium who underwent a total of 37 modified Heyman packings treated on a high dose rate Microselectron has been reviewed. Using computed tomography (CT), the uterine wall thickness was measured retrospectively and doses calculated at a number of points on the uterine serosa and related normal tissues. The mean and maximum fundal serosal doses were found to be highest posteriorly and the sigmoid colon was adjacent to the posterior surface of the uterus in all instances. By superimposing the isodose distribution on CT sections of the uterus, it is now possible to prescribe to a serosal dose, or, in patients too heavy for the CT scanner, a dose can be prescribed to a point S, which is a reasonable approximation to the serosal position. Since the initial study, a further ten patients have been treated by the same method and, where relevant, data from all 33 patients have been used.

Community acquired pneumonia: aetiology and prognostic index evaluation.

A 10 month prospective study of all adults admitted to Waikato Hospital with community acquired pneumonia was performed to assess aetiology, mortality, hospital stay, and the value of a prognostic index based on that obtained from a British Thoracic Society study. The 92 patients in the survey had a mean age of 56 (range 13-97) years. A microbiological diagnosis was established in 72%; Streptococcus pneumoniae (33%), Mycoplasma pneumoniae (18%), and influenza A virus (8%) were the most common microorganisms. Other causative organisms were Legionella pneumophila (4 cases), Staphylococcus aureus (3), Klebsiella pneumoniae (2), Haemophilus influenzae (2), Nocardia brasiliensis (1), and Acinetobacter calcoaceticus (1). Chlamydia sp, influenza B virus and adenovirus were each found in one case; all were cultured on nasopharygeal aspirates. Aspiration was considered to be the underlying cause in five patients, two with epilepsy and one with pseudobulbar palsy. Five of the six deaths that occurred were in patients over 75 years of age and the other was 69. In four of the six the established causative organisms were Chlamydia sp (1), K pneumoniae (1), and S aureus (2). Patients had a 16 fold increased risk of death if they had two or more of the following on admission: a respiratory rate of 30/minute or more, diastolic blood pressure of 60 mm Hg or less, and either confusion or a plasma urea concentration greater than 7.0 mmol/l.

Concomitant pelvic irradiation, 5-fluorouracil and mitomycin C in the treatment of advanced cervical carcinoma.

This was a Phase II study of 24 late (FIGO) Stage IIb and 39 Stage III patients. External beam radiotherapy was given daily, five days a week, using 15 x 15 cm parallel opposed pelvic fields. The first 20 patients had 45.00 Gy mid-plane dose in 20 fractions, Days 1-28, the last 43 patients had 50.40 Gy in 28 fractions, Days 1-43. This was followed by an intracavitary boost of 17.00 Gy to Point A in two fractions over seven days. The first seven patients had concomitant 5-fluorouracil (5FU) 1 g/m2/day (maximum 1.5 g/day) Days 2-5, 30-33 and 57-60, with mitomycin C 10 mg/m2 (maximum 15 mg) Days 2 and 57. Two patients had WHO Grade 4 cytopenia, and only two were able to have full dose intensity. The 5FU dose was reduced to 0.8 g/m2/day, for Days 2-5 and 30-33; mitomycin C was given on Day 2 only. Treatment morbidity with the reduced chemotherapy intensity was comparable with that of radiotherapy alone. Median follow-up was 16 months (range 6-44). Median survival was 35 months. The results were compared with historical controls treated using the same radiation method alone. Two-year survival for late Stage IIb patients was 67% with the combination and 72% with radiotherapy alone; for Stage III, 67% and 49% respectively. Two-year pelvic control for late Stage IIb was 87% (combination) and 84% (radiotherapy alone) and for Stage III, 61% and 55% respectively. In contrast to reports from other centres, these results do not show an overall significant improvement on radiotherapy alone. A Phase III study may not be practicable.

Diurnal variation and interrelations of ecophysiological parameters in three peatland woody species under different weather and soil moisture conditions.

The diurnal patterns of twig xylem water potential, net photosynthesis rate, water use efficiency of photosynthesis, and stomatal and mesophyll conductance to CO2 in tamarack, black spruce and swamp birch growing in a natural peatland in central Alberta, Canada, were examined. The relationships of photosynthesis to other ccophysiological parameters were investigated. Data were collected on three days with different weather and soil moisture conditions in the 1988 growing season. Day 1 was clear and warm and the ground water table was 7 cm above the average peat surface. Day 2 was clear and hot. Day 3 was cloudy but warm. On day 2 and day 3, the water tables were in the normal range for that season. Major findings were: 1) Soil flooding depressed photosynthesis in tamarack and black spruce. 2) Swamp birch was better adapted to flooding than tamarack or black spruce. 3) The trees experienced water stress in the afternoons of the two days with lower water table. 4) Changes in photosynthesis of the three species were primarily affected by changes in mesophyll conductance (gm) and the response of photosynthesis to changes in gm was similar for all three species.

'Safe oxygen' in acute asthma: prospective trial using 35% Ventimask prior to admission.

There is still some uncertainty as to the best inspired oxygen concentration to use in the treatment of acute asthma before measurement of arterial blood gases can be made. In the absence of published data, we report a prospective study in which 35% oxygen was the initial therapy given to patients with moderate to severe asthma, and arterial blood gases were taken to assess the adequacy of oxygenation and the safety of this method. Forty-five episodes were analyzed and a wide range of PaO2 was observed (8.8-21.3 kPa 66-160 mmHg). No relationship was shown between PaCO2 and either PaO2 or duration of oxygen treatment. It was concluded that 35% oxygen given in acute asthma is both safe and probably adequate. A lesser concentration of oxygen could expose asthmatics to an unacceptable risk of significant hypoxaemia.

Lessons from the national asthma mortality study: deaths in hospital.

The circumstances surrounding 38 deaths from asthma in hospital in New Zealanders under 70 years of age between August 1981 and July 1983 have been analysed. Twelve deaths did not appear to be preventable, all but one occurring in chronic severe asthmatics despite apparently optimal therapy. Critical delays by patients or relatives in seeking medical help occurred in six cases, and inadequate assessment of severity and undertreatment by medical practitioners prior to the patient reaching hospital was a major contributing factor in a further six deaths. In four cases, insufficient speed and indecisive treatment in the accident and emergency department appeared to contribute to death. Ten patients died after many hours or days in hospital wards in circumstances where assessment, monitoring and treatment were deficient. There were no deaths in intensive care units. Urgent expert assessment is necessary in A & E departments, and more severe cases should be managed in intensive care units. Patients with acute severe asthma may need continuous oxygen, intravenous therapy and close objective assessment for a week or more after hospitalisation.

Flow cytofluorometric evidence for the differential radioresponsiveness of aneuploid and diploid cervix tumours.

We are presently involved in a prospective study of the relationship between DNA content profiles, and their changes during treatment, determined by flow cytofluorometry, and patient prognosis and response to therapy for cancer of the uterine cervix. To date, 348 patients have been included in the study over a 54-month period. Data on these patients have shown that DNA aneuploid tumours are significantly more radioresponsive than diploid cervix tumours. Analysis of the data on 213 patients with a minimum follow-up time of 15 months has, however, failed to show an overall more favourable prognosis conferred by tumour DNA aneuploidy. Analysis of the relationship between clinical stage and disease state and tumour DNA ploidy, however, suggests that aneuploid tumours metastasize to distant sites at an earlier stage of the disease than diploid tumours and local recurrence rates for diploid tumours, in late stage disease, are double those for aneuploid tumours. Improved staining procedures, and instrument modification, has also shown that cervix tumour heterogeneity is of considerably greater frequency than at first appeared to be the case (approximately 75% of DNA aneuploid tumours show heterogeneity.

75 deaths in asthmatics prescribed home nebulisers.

The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma.

Lessons from the national asthma mortality study: circumstances surrounding death.

The circumstances surrounding all deaths from asthma in New Zealanders under 70 years of age between August 1981 and July 1983 have been analysed from information recorded or recalled by doctors or relatives of the deceased. Factors which may have reduced the time available for effective treatment of these severe attacks are described to draw attention to ways in which mortality might be reduced. For almost half of the 271 deaths medical help had not been called before the patient was in extremis. When medical help was summoned in sufficient time doctors commonly did not give corticosteroids or used them inadequately. Difficulties in using medical care and noncompliance with asthma management were common particularly in Polynesian patients. In 38% of patients some medical inadequacy appeared to contribute to poor long-term care and education. Failure of patients to attend for ongoing medical care, education and preventative treatment, or a medical failure to deliver these may have led to chronically reduced lung function. Any further deterioration may then have more rapidly led to a fatal outcome. Lack of patient or family awareness about how to detect and cope with an unusually severe attack was found and contributed to avoidable fatalities.

Accuracy of certification of deaths due to asthma. A national study.

In a two-year study of asthma mortality in New Zealand conducted between August 1981 and July 1983, the certified cause of death and its subsequent statistical coding was compared with the opinion of a panel of respiratory physicians who had made detailed enquiry into the medical history and circumstances surrounding the death of each patient. When the panel's opinion was taken as the reference standard, the national health statistics overestimated asthma mortality for all age groups by 26.0%. For patients aged 15-64 years, the net overestimate was 12.9%, no greater than that found in a similar study in this age group in the United Kingdom. Failure of certifying doctors and coroners to follow appropriate procedures for identification of the primary condition leading to death, or misdiagnosis of other lung disease as asthma, accounted for most inaccuracies in certification. In patients under age 35 years, certification and statistical coding of asthma death was considered accurate in 97.8% of all cases, but accuracy declined with increasing age. The high New Zealand asthma mortality rate, especially in young people, could not be explained by inaccuracies in death certification or statistical coding.

Asthma mortality: comparison between New Zealand and England.

Causes for the high mortality from asthma in New Zealand were investigated by comparing deaths from asthma in caucasian subjects aged 15-64 in New Zealand with those from asthma in the same age group in two regions in England. There were no significant differences in the accuracy of death certification. The verified asthma mortality in New Zealand (4.2/100,000) was over twice that in England. Many characteristics of patients and management, including poor compliance with treatment and deficiencies in long term and emergency care, were qualitatively similar in the two countries. New Zealand had an apparently higher rate of non-preventable deaths from asthma, suggesting a greater severity of asthma in New Zealand. In both countries, however, most deaths were associated with poor assessment, underestimation of severity and inappropriate treatment (over-reliance on bronchodilators and underuse of systemic corticosteroids), and delays in obtaining help. A greater frequency of some of these deficiencies in management remains a possible additional explanation for part of the excess mortality in New Zealand.

The growth and cellular kinetics of human cervical cancer spheroids in relation to drug response.

A methodology for culturing multicellular spheroids directly from tumour biopsy material has been established with a success rate of 82% for cervical carcinomas. Spheroids, selected for uniform size and shape, have been subjected to quantitative assay to determine their population dynamics using 3H-Tdr autoradiography and have also been treated with 13 commonly used anti-cancer drugs. Several characteristics of cervical spheroids, e.g. growth rate, labelling index, thickness of viable cell rim, were similar for drug responding and non-responding spheroids but the faster growing spheroids responded to an increased number of types of drugs. Spheroids derived from poorly differentiated tumours also showed an increased response to drugs compared to those from moderate or well differentiated tumours.

Deaths from asthma in New Zealand.

We report the first complete population based study of childhood deaths due to asthma. All deaths ascribed to asthma in New Zealand children aged 0-14 were investigated as part of a two year national study of mortality from asthma. The 16 children who died from asthma all developed asthma by the age of 4; 15 had a family history of asthma, and 12 had associated atopic disorders. Disturbed pyschosocial relationships were evident in eight families. Seven children died in less than three hours from the onset of their final attack. All children died outside hospital. Mortality from asthma in Maori children (3.14 per 100 000) was five times that of European children. With hindsight, factors which if avoided could have led to a different outcome were identified in eleven cases. The circumstances surrounding these deaths were similar to those described for adults with asthma; this study, however, underlines the importance of parental care and knowledge in the management of children with asthma. Inadequate long term medical care, underassessment of severity by family and doctors, failure of the family to call for help when required, and inadequate responses of medical services contributed to the fatalities. Excess beta2 sympathomimetic dosage or overreliance on home nebulisers were uncommon. Most childhood deaths from asthma should be prevented by increased family awareness, better assessment of severity, improved long term treatment, and rapid access to emergency medical care.

Radiation pneumonitis in patients treated for breast cancer.

An analysis of 201 breast cancer patients having post-operative radiotherapy to the chest wall between January 1981 and May 1983 has identified those patients with chest symptoms following radiotherapy and these have been critically assessed with regard to the possibility of radiation pneumonitis being their cause. The inner contour of the anterior chest wall has been reconstructed on the radiation plan and the area of lung irradiated to a significant level in the mid-plane of the tangential fields determined. The incidence and severity of pneumonitis has been shown to rise exponentially with increase in the irradiated volume. A method of measuring the thickness of the chest wall using the simulator has been devised so that this information may be incorporated into the planning process in order to reduce the area of lung at risk.