The effects of Euphorbia hirta on the ultrastructure of the murine liver, kidney and aorta.

Euphorbia hirta is widely used in traditional remedies and has been used cross-culturally for generations against maladies such as asthma, skin ailments and hypertension. Previous studies have demonstrated that Euphorbia hirta has antibacterial activity, and have also indicated certain antimolluscidal, antimalarial and anti-inflammatory properties, the latter of which have been suggested to be more pronounced than those of the rheumatological drug, etanercept. To date, no studies have identified the anatomical effects of this herb on the organs of test animals. This study aimed to identify the effects of Euphorbia hirta on the ultrastructure of the murine liver, kidney and aorta. A total of 32 adult male Sprague-Dawley rats were divided into four groups; three groups were fed with aqueous extracts of Euphorbia hirta at doses of 1, 10 and 50 mg/kg, respectively, every alternate day for 50 days, while one group served as a control. The animals were later sacrificed and the liver, kidney and aorta harvested for examination by electron microscopy. The aorta showed no ultrastructural changes across the groups. Renal and hepatic tissue from the treated groups demonstrated dose-dependent injuries, which showed architectural damage beginning in the nuclei and spreading outwards. Taking into consideration the properties of Euphorbia hirta that have been described in previous studies, in addition to the results from the present study, it appears that the herb may exhibit similar effects to those of the quinolone group of antibiotics. Further in-depth investigations are required into the potential effects of Euphorbia hirta, deleterious and otherwise.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

A preliminary finding: immunohistochemical localisation and distribution of placental angiotensin II receptor subtypes in normal and preeclamptic pregnancies.

Pre-eclampsia or pregnancy induced hypertension (PIH) affects 6-8% of all pregnancies. Although the underlying mechanism of PIH is still unknown, it is widely believed that the placenta plays an important role. It was thought that an ischemic placenta due to poor perfusion can precipitate the signs and symptoms of PIH. This study aims to investigate the possible role of Type 1(AT1) and Type 2 (AT2) angiotensin II receptor subtypes in the mechanism of PIH. AT1 receptor stimulation causes vasoconstriction and AT2 receptor stimulation causes vasodilatation. Investigating the interactions of these two receptors in the placenta provides an insight as to the balance that may exist between AT1 and AT2 receptors in normal pregnancy. Any disruption to the balance might cause a disruption of the blood flow in the placenta, leading to PIH. Placentas were collected from 11 PIH patients and 11 normal patients. Immunohistochemistry techniques were performed on the placental tissue to determine the distribution of AT1 and AT2 receptors in the placental tissue qualitatively and quantitatively. It was observed that in normal patients, the balance between AT1 and AT2 receptors is that the level of AT2 receptors is higher than the level of AT1 receptors. However in the PIH patient, it was observed that the normal balance was disrupted. In PIH patients the level of AT1 receptors was observed to be higher than the level of AT2 receptors. This study suggests that disruption of the balance between AT1 and AT2 receptors observed in PIH placentas might cause a decrease in blood flow to the placenta, causing it to be poorly perfused. This may cause placental ischemia which may lead to PIH.

Is early enteral feeding safe in patients who have suffered spinal cord injury?

OBJECTIVE: To examine whether enteral feeding is a safe technique to use in the acute stage of spinal cord injury. METHODS: We searched the departmental computerised patient database and clinical records for all patients with spinal cord injuries admitted to the Auckland Hospital Intensive Care Unit (ICU), known as the Department of Critical Care Medicine (DCCM), between January 1988 and December 2000. Patients were included in the study if they had suffered complete spinal cord transection resulting in either paraplegia or quadriplegia. Data was collected for the following variables: length of time to commence enteral feeding, type of enteral feeding, duration of enteral feeding and reasons for interrupting the feed. RESULTS: Thirty-three patients were found and were included in the study. Twenty-seven (82%) of the patients commenced enteral feeding in the DCCM, 25 by nasogastric (NG) and 2 by nasojejunal (NJ) tube. Feeding was commenced a median of 2 days after admission and the median length of enteral feeding was 7.7 days. The main feeding complications that resulted in interrupting the feed were high gastric aspirates. One patient commenced on enteral feeding developed medical complications that prevented continuation. Two patients on NG feeding converted to NJ feeding. CONCLUSION: No major complications associated with enteral feeding were seen in this study. This would indicate that enteral feeding can be safely administered in the acute stage of spinal cord injury provided complications are monitored for daily.

The role of bilateral adrenalectomy in the treatment of congenital adrenal hyperplasia.

This report summarizes follow-up studies in 18 patients who underwent bilateral adrenalectomy for congenital adrenal hyperplasia. Three of these patients were young children with null/null mutations of CYP21, and the other 15 were adrenalectomized because of difficulties in their management on conventional therapy. The average duration of follow-up was 59 months and represents an aggregate of 90 postoperative years. The adrenals were removed laparoscopically in 13 patients and by open flank incisions in five. Adrenal crises associated with severe illnesses occurred in five patients at times when their glucocorticoid substitution was suboptimal. All were responsive to appropriate therapy. Two of these patients were young children who had hypoglycemia during gastroenteritis or febrile illness associated with poor food intake or vomiting. Significant elevations of adrenal steroid precursors, presumably from ectopic adrenal rests, were observed postoperatively in eight of the patients. Patients and parents were nearly unanimous in their enthusiasm for adrenalectomy. In most, signs of androgen excess have decreased, and obesity has become less of a problem with lowering the dose of glucocorticoid. We conclude that adrenalectomy is a safe and efficacious method of managing congenital adrenal hyperplasia in selected patients. Prophylactic adrenalectomy in young children with double null mutations remains experimental.

A decade of intensive care unit trauma admissions in Auckland.

AIMS: To describe the demographics, nature and severity of injury of trauma admissions to a New Zealand urban Intensive Care Unit (ICU) over a ten year period; to determine differences in injury characteristics between patients received from inside and outside the local trauma catchment area; and to calculate incidence rates in the local population served, to identify high risk groups of patients. METHODS: We carried out a cross-sectional analysis of a prospective ICU patient registry. Data on all trauma admissions from 1988 to 1997 to the ICU of a large New Zealand urban hospital were studied with respect to age, gender, ethnicity, injury type and severity, and referral status. National Census data for the ICU catchment area were used to calculate incidence rates for local admissions. RESULTS: A total of 2305 trauma patients were admitted over the period of the study, accounting for 25% of all ICU admissions. The median age was 28 years and 75% were males. Blunt trauma, mostly due to motor vehicle crashes, accounted for 95% of admissions and penetrating trauma was very rare. The median Injury Severity Score (ISS) was 26 and most life threatening injuries occurred in the head region. Referred admissions were more severely injured and had a higher prevalence of severe head injury than local admissions. The ICU trauma admission rate for local patients was 34.6 per 100,000 person-years. Males had a higher rate than females in all age groups. New Zealand Europeans made up the majority of admissions, but Maori and Pacific Island males had the highest incidence rates. CONCLUSIONS: This study identified trauma as a major component of the ICU population. ICU trauma admissions were characterised by young males with head injuries resulting from motor vehicle crashes. Referred admissions were more severely injured than local admissions and would thus distort the estimated incidence of trauma in the local geographic region served. Calculation of incidence rates highlighted a significantly higher risk of ICU trauma admission amongst Maori and Pacific Islands people than New Zealand Europeans.

Changing patterns of severe craniomaxillofacial trauma in Auckland over eight years.

BACKGROUND: This study was performed to review the changing pattern of incidence of severe craniomaxillofacial (CMF) trauma in Auckland over 8 years (1989-1997) and to audit the involvement of the regional plastic surgery service. METHODS: A review of prospectively collected admission data of patients admitted to the Auckland Hospital Department of Critical Care Medicine (DCCM) with severe CMF trauma during 1997. A comparison is made with similar data from 1989. Injury severity was defined using the Injury Severity Score (ISS). RESULTS: Twenty-six patients with severe CMF trauma were admitted to Auckland Hospital DCCM in 1997. Their average ISS was 35. Eighty per cent had a significant head injury. Sixty-two per cent had injuries due to road traffic accidents (RTA) and 42% had positive blood alcohol levels, including 37% of the RTA victims. Twenty-three per cent had their surgical care provided by the regional plastic surgery service. In 1989, 55 patients were admitted to DCCM with severe CMF trauma. The average ISS was 36. Ninety-five per cent had a significant head injury. Seventy-three per cent had injuries due to RTA and 55% had positive blood alcohol, including 60% of the RTA group. CONCLUSIONS: Patients with severe CMF trauma make up a significant proportion of trauma admissions to DCCM and have a high incidence of life-threatening injuries. A multidisciplinary approach is essential. The nature and severity of these injuries has not changed over the last decade. There has been a clear decrease in the incidence of these injuries. This seems to be due to a profound decrease in the rate of RTA associated with alcohol intoxication.

Elderly trauma patients admitted to the intensive care unit are different from the younger population.

AIMS: This study was undertaken to investigate the demographic profile of elderly (65 years old and over) patients with severe trauma admitted to the Intensive Care Unit of Auckland Hospital and to compare their characteristics with those of the younger (under 65 years) trauma patients. A further aim was to see if specific areas of potential injury prevention could be identified. METHOD: Data analysis covering ten years, from January 1987 to December 1996, on data extracted from the existing database at the Intensive Care Unit of Auckland Hospital. RESULTS: The elderly comprised 8.7% (183 of 2092) of the trauma admissions during the study period. The elderly, when compared with the younger group, were significantly more likely to be female, New Zealand European and admitted as a result of a fall. They were significantly less likely to be drivers in a road traffic crash or, if a driver, to have a blood alcohol above the legal limit. Mortality in the older group (27.8%) was significantly higher, though median injury severity score (25) and length of stay (57.9 hours) were similar. CONCLUSIONS: Elderly trauma patients in the Intensive Care Unit are a group with distinctive demographics, mechanisms of injury, injury types and outcomes. This information needs to be considered for the future planning of trauma and prevention services in New Zealand.

Cost comparison of antibacterial therapies for serious infections. A New Zealand 3-hospital study.

OBJECTIVE: The first aim was to identify and determine the economic costs of the regimens currently used in 3 New Zealand hospitals in the treatment of bacterial infections in haematology patients with febrile neutropenia and in intensive care patients with severe infections. The second was to develop a spreadsheet-based decision analytic model for use by hospital decision-makers as an aid in evaluating the comparative cost of drug regimens. DESIGN AND SETTING: The research utilised time and motion and microcosting techniques. The analytical perspective adopted for the study was that of a hospital administrator or clinical manager. PATIENTS AND INTERVENTIONS: Patients were eligible for inclusion in the study if either they were treated with the imipenem/cilastatin monotherapy, or could have been treated with this regimen. The final analysis considered 360 patient-treatment days and 8 antibacterials. MAIN OUTCOME MEASURES AND RESULTS: Drug acquisition cost ranged from 4.52 New Zealand dollars ($NZ; 1997 values) per patient-treatment day for gentamicin to $NZ104.81 for imipenem. The cost per patient-treatment day (when other cost components such as fluid additives, giving sets and needles were added) ranged from $NZ8.75 for gentamicin to $NZ129.12 for tazobactam. Drug acquisition cost, as a percentage of total drug preparation and administration cost, ranged from 52% for gentamicin to 93% for piperacillin. Giving sets and intravenous (i.v.) fluids were found to be important cost items when they were required specifically for the treatment regimen. There was a mean monitoring rate of 0.40 at a cost of $NZ6.41 per patient-treatment day for gentamicin. It was estimated that nephrotoxicity could add between $NZ23 and $NZ43 per day to the cost of aminoglycoside treatment. CONCLUSIONS: Although the small sample sizes of the study mean that results should be regarded as indicative rather than conclusive, there were sufficient information to construct a working model and show how the total cost of an antibacterial regimen could be evaluated in practical terms. The important cost drivers were found to be drug cost, the use of fluids and giving sets, and monitoring.

Cost containment: the Pacific. New Zealand.

New Zealand is a small nation with an extensive state-funded system of health, education, and welfare that is currently under "reform." The healthcare system remains largely government-funded and is free to all New Zealand residents. Healthcare spending accounts for approximately 7.4% of the country's gross domestic product and has not changed in the last 5 yrs. Ninety-three percent of New Zealand's ICUs are in public hospitals, where ICU beds constitute 0.9% of the total number of beds. In all, there are 43 ICU beds/1 million inhabitants. Between 1989 and 1992, the number of public hospital beds decreased by 19% and the number of ICU beds decreased by 5%. ICU Resources have been limited for many years, and clinicians have responded by attempting to prevent disease and limit its severity, by vetting (and declining) requests for ICU admission, by reducing length of ICU stay of both survivors and nonsurvivors, and by reducing marginal costs. Both limiting and actively withdrawing therapy are well established practices in New Zealand ICUs. The country's physicians are conservative in their use of new technology but demand excellence and value in equipment. ICU technology and knowledge diffuse easily throughout New Zealand because of the country's geography and population distribution, in addition to the activities of the Australian and New Zealand Intensive Care Society (ANZICS) and the defined specialty training pathways for intensive care. Hospital care is relatively cheap and nurse extenders, respiratory therapists, and ward pharmacists are not used. Flow charts in the ICU are custom-designed and not computerized, but computers are increasingly being used for clinical databases and ICU policy development.

Grading asthma severity: using the APS component of the Apache II system.

OBJECTIVE: Measurement of severity is fundamental to the description and comparison of case series, treatment regimens and disease outcomes. This study examines the Acute Physiology Score (APS) as a severity measure of an acute "life-threatening" asthma attack. DESIGN: The APS in the emergency department (ED) and ICU, demographic, treatment and outcome variables were prospectively studied. Relationships between severity, treatment and progress were investigated. In addition, patients were stratified according to ED APS and differences between the participating hospitals were examined. SETTING: Emergency Departments and Intensive Care Units of two New Zealand hospitals. PATIENTS: 64 admissions to the ICUs following an acute episode of asthma. INTERVENTIONS: Standard management of acute asthma as practised at the two participating hospitals. MEASUREMENTS AND RESULTS: Both the treatment delivered (intravenous salbutamol, sodium bicarbonate and IPPV) and the rate of improvement as defined by change in APS between the ED and the ICU were found to be strongly related to ED APS. Similarly, the length of stay in the ICU correlated with the ICU APS. Stratification on the basis of ED APS allowed small but significant differences in patient physiologic derangement, dose of salbutamol, use of IPPV and incidence of complications to be detected between patients at the two hospitals. CONCLUSION: This prospective study involving two hospitals validates the APS as a method for measuring the severity of an acute asthma attack. It demonstrates how correction for severity can be used to compare treatment and outcome variables in different case series.

Critical injuries in paediatric pedestrians.

Data are presented on all sixty-four children who were injured as pedestrians and admitted to the department of critical care medicine, Auckland Hospital over a four year period. Median age was six years, with a male:female ratio of 1.6:1.0. Admission rates were 3.1 and 3.0 times higher for Maori and Pacific Island children, respectively, than for children of European origin. Fifty-two percent of injuries occurred between 3 pm and 7 pm. Median injury severity score (ISS) was 29, and 95% of patients had an ISS of 16 or more. Life threatening injuries were most commonly to the head, whilst less severe injuries, commonly fractures, were to the limbs. The combination of head and lower limb injury was seen in 53% of patients. Twenty-nine patients had 34 operative procedures: 16 orthopaedic, six neurosurgical, four laparotomies and eight wound debridement and closure. Eighty-one percent of the patients received ventilatory support and nine patients (14%) died, all from brain injuries. Pedestrian injury is an important child health problem in New Zealand and studies aimed at the identification of factors that place children at risk for these injuries are needed.

A comparison between electroencephalography and somatosensory evoked potentials for outcome prediction following severe head injury.

The value of somatosensory evoked potentials (SEPs) for the prediction of outcome following severe head injury (HI) is established. The role of the electroencephalogram (EEG) in this setting is uncertain. In this comparative study, SEPs and EEGs were recorded within 3 days of severe HI in 90 patients, and the results related to outcome at 6 months. Patients with an isoelectric EEG or an EEG with repeated isoelectric intervals died. Reactivity of the EEG to external stimulation tended to be associated with favorable outcome. Grading of the EEGs on the basis of frequency composition otherwise provided no prognostic information. The presence of SEP scalp potentials bilaterally predicted favorable outcome, particularly if the central conduction times were normal. Conversely, the absence of one of both scalp potentials was associated with unfavorable outcome. EEGs thus provided useful prognostic information in only a minority of patients. By comparison, SEPs allowed prediction of both favorable and unfavorable outcomes in a much larger number of patients, and were therefore prognostically superior.

Early prediction of outcome from cerebral trauma by somatosensory evoked potentials.

The prognostic value of short-latency somatosensory evoked potentials (SEP) during the first 4 days after severe head injury was studied in a group of 100 ICU patients. There was a strong association between the presence of bilateral cortical potentials and a good recovery or moderate disability 6 months after injury. In contrast, the bilateral or unilateral absence of cortical potential was associated with severe disability, persistent vegetative state, or death in a high percentage of patients. A reliable prediction of outcomes was obtained from SEP recorded within 24 h of head injury. Predictive accuracy was not influenced by the time of recording or cumulative analysis of consecutive daily SEP over the first 4 days after injury. Short-latency SEP can provide a reliable and accurate prognosis for sedated and curarized patients, and can have an important role in the management and triage of patients with severe head injury who are undergoing intensive therapy.

A comparison of AIS-85 with AIS-80 for injury scaling in blunt trauma.

As the effects on injury scaling of the differences between the 1980 and 1985 revisions of the AIS are unknown in blunt trauma, we compared them in all 1270 critically injured (median ISS, 26) blunt trauma patients (75% male, 74% road crash, overall mortality 17%) admitted to the Department of Critical Care Medicine at Auckland Hospital from 1983 through 1987. In 911 patients (72%) there were no differences between AIS-80 and AIS-85 in any body region or in derived ISS. Changes in AIS grades were most common in the abdomen (205 patients), thorax (100 patients), and head (61 patients) regions. Median ISS overall for the 1270 patients was unchanged at 26. One percent of patients had changes in ISS of 16-24 points. Direct comparison of groups of patients scored with these two revisions of the AIS is inappropriate, particularly in those with abdomen region injury.