Postoperative epidural analgesia following elective major abdominal surgery in high risk patients: a retrospective cohort study

AIM: To describe the effect of post-operative epidural analgesia on morbidity and mortality rates in a group of high-risk patients undergoing elective major abdominal surgery. METHODS: Retrospective chart review of patients in American Society of Anaesthetists Physical Status (ASA) category III or IV, who underwent elective major I or II general surgical procedures between 01/01/1996 and 01/09/1998. Patients were identified from a prospective audit database. Patients who had epidural analgesia or conventional parenteral opioids were compared for outcome measures. RESULTS: There were 167 patients identified (72 epidural, 95 non-epidural group). There was no significant difference in demographic data, inpatient stay, intensive care unit stay, or mortality rates (11% epidural v 17% non-epidural, p>0.05). There was no significant difference in morbidity rates, however there was a non-significant trend towards a lower morbidity in the epidural group. CONCLUSIONS: This study does not show any benefit from post-operative epidural analgesia on morbidity and mortality rates in high risk patients undergoing major abdominal surgery. It does illustrate that ASA 3 and 4 patients undergoing major abdominal surgery have a high morbidity and mortality.     

Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design,synthesis, and X-ray cocrystal structure

A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against cancer cell lines.     

Comparison of the microvasculature of basal cell carcinoma and actinic keratosis using intravital microscopy and immunohistochemistry

BACKGROUND: Angiogenesis is a prerequisite for growth of invasive tumours. We hypothesized that angiogenesis would be present in invasive basal cell carcinoma (BCC) but not in a noninvasive tumour such as actinic keratosis (AK). OBJECTIVES: To investigate both types of tumour for evidence of angiogenesis. METHODS: Patients with BCC or AK underwent intravital videocapillaroscopy. Three regions were examined: the tumour, perilesional skin and a control site. Microvessel width, area fraction and length density were determined from capillaroscopy images. Biopsies were stained for CD34 and a microvessel count was performed. RESULTS: Capillaroscopy demonstrated a grossly disorganized tumour microcirculation in BCC. Compared with control skin, microvessel width was increased 2.4-fold, area fraction was increased 4.9-fold and length density was increased 5.9-fold. In AK, microvessel width was increased 1.7-fold, area fraction 2.5-fold and length density 3.4-fold. Vessel width and area fraction were significantly greater in BCC than AK. Biopsies showed significant increases in microvessel length density for both BCC and AK compared with control skin, with BCC significantly greater than AK. CONCLUSIONS: Angiogenesis was demonstrated in BCC in humans in vivo, and to a lesser extent in AK.     

High-resolution CT features of severe asthma and bronchiolitis obliterans

AIM: To evaluate the high-resolution CT findings of severe asthma (SA) and bronchiolitis obliterans (BO) and determine whether any reliable discriminating HRCT features exist. MATERIALS AND METHODS: HRCT examinations of the chest of 30 patients with SA and 14 patients with BO were analysed. Images were scored for the presence and extent of 21 CT findings. RESULTS: The most consistent HRCT features in SA were bronchial wall thickening in 30 (100%), expiratory air trapping in 19 of 22 examinations with expiratory images (87%), inspiratory decreased attenuation in 18 (60%), and bronchial luminal narrowing in 12 (40%). The most consistent HRCT features in BO were expiratory air trapping in 10 of 10 examinations with expiratory images (100%), bronchial wall thickening in 13 (93%), inspiratory decreased attenuation in 11 (79%), ground glass opacity in seven (50%), and mosaic pattern of attenuation in seven (50%). Decreased attenuation was more extensive in BO than in SA on both inspiratory and expiratory images. The mosaic pattern of attenuation was present in seven (50%) BO patients but in only one (3%) SA patients (P=0.0006). CONCLUSIONS: Mosaic pattern of attenuation, when present, is highly suggestive of BO, but SA and BO may be indistinguishable.     

The relationship between disease control strategies and health system development: the case of TB

This paper focuses on the lack of dialogue and policy consonance between those taking the lead in health systems change and those developing specific disease control strategies. In the first part, the origins and characteristics of this situation are explained using, as an example, TB control. Attention is then paid to the development of disease control friendly health systems. Four aspects of policy development are analysed paying particular attention to TB control: analysis of policy context, mechanisms for collaboration between policy actors; agreement on decision-making processes; development of common aims and objectives. Although the focus is on TB control, the principles illustrated carry some relevance for other disease control programmes.     

Decreased telomerase activity is not a reliable indicator of chemosensitivity in testicular cancer cell lines

Telomere stabilisation is a critical step in tumorigenesis and telomerase, an enzyme which counteracts telomeric DNA loss, is active in most tumours. Conflicting evidence has been published concerning the potential use of telomerase activity as a measurement of drug-induced tumour cell killing. In this study, the time courses of telomerase loss and induction of apoptosis were investigated in two testicular cell lines, Susa CP and 833 K, following 4-h exposure to cisplatin, melphalan or doxorubicin. Telomerase activity was only affected in both cell lines at 20 h following exposure to high concentrations of cisplatin (100x the drug concentrations causing 50% growth inhibition (IC(50) values)). The time course of melphalan-induced telomerase loss, which was again only apparent at 100x IC(50) concentrations, varied between the cell lines and doxorubicin (100x IC(50)) did not induce telomerase loss in either of the cell lines. Importantly, the levels and rates of appearance of apoptotic cells (nuclear morphology and annexin V staining) were similar for all three drugs in both cell lines; i.e. cisplatin, melphalan and doxorubicin (100x IC(50)) caused similar frequencies of apoptosis in Susa CP cells at 24 h whereas telomerase activities were 65, 123 and 96% of the control, respectively. The possibility that telomerase activity was lost following cisplatin treatment through a direct interaction of cisplatin with telomerase was discounted. Additionally, the relative levels of the RNA component of telomerase (hTR) and mRNA for the telomerase catalytic subunit (hTERT) were not related to the observed decreases in telomerase activity. These data indicate that telomerase activity is not a reliable indicator of chemosensitivity in human testicular cancer cells. Furthermore, cisplatin-induced loss of telomerase activity is not due to a direct reaction with the enzyme or decreased hTR levels.     

A systematic review of current knowledge of HIV epidemiology and of sexual behaviour in Nepal

OBJECTIVE: To systematically review information on HIV epidemiology and on sexual behaviour in Nepal with a view to identifying gaps in current knowledge. METHODS: Systematic review covering electronic databases, web-based information, personal contact with experts and hand searching of key journals. RESULTS: HIV-1 seroprevalence has been rising rapidly in association with high-risk behaviours, with current levels of 40% amongst the nation's injecting drug users and approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV seroprevalence remains low in the general population (0.29% of 15-49 year olds). There are significant methodological limitations in many of the seroprevalence studies identified, and these estimates need to be treated with caution. There are extensive migration patterns both within the country and internationally which provide the potential for considerable sexual networking. However, studies of sexual behaviour have focused on FCSWs and the extent of sexual networks within the general population is largely unknown. CONCLUSIONS: Whilst some of the ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge on sexual behaviour in the general population is missing. Research on sexual networking is urgently required to guide HIV control in Nepal. There is also a need for further good-quality epidemiological studies of HIV seroprevalence.     

Dynamic cerebral autoregulation in healthy adolescents

BACKGROUND: : There is little information on the limits of cerebral autoregulation and the autoregulatory capacity in children. The aim of this study was to compare dynamic cerebral autoregulation between healthy adolescents and adults. METHODS: : Seventeen healthy volunteers 12-17 years (n = 8) and 25-45 years (n = 9) were enrolled in this study. Bilateral mean middle cerebral artery flow velocities (Vmca; (cm/s)) were measured using transcranial Doppler ultrasonography (TCD). Mean arterial blood pressure (MAP) and end-tidal carbon dioxide were measured continuously during dynamic cerebral autoregulation studies. Blood pressure cuffs were placed around both thighs and inflated to 30 mmHg above the systolic blood pressure for 3 min and then rapidly deflated, resulting in transient systemic hypotension. The change of Vmca to change in MAP constitutes the autoregulatory response, and the speed of this response was quantified using computer model parameter estimation. The dynamic autoregulatory index (ARI) was averaged between the two sides. RESULTS: : Adolescents had significantly lower ARI (3.9 +/- 2.1 vs. 5.3 +/- 0.8; P=0.05), and higher Vmca (75.2 +/- 15.2 vs. 57.6 +/- 15.0; P<0.001) than adults. CONCLUSION: : The autoregulatory index is physiologically lower in normal adolescents 12-17 years of age than in adults.     

Huli oral health

The Tari oral health study was conducted in 1985 and aimed to provide an oral health profile of a rural highlands community. The sample was selected from the database of the Tari Research Unit, Southern Highlands Province, Papua New Guinea and consisted of 815 Huli people aged from 3 to 64 years, in seven age groups, who were examined for oral health status and had completed an interview-questionnaire. A wide range of oral health status was seen, ranging from excellent to very poor. Dental caries and periodontal disease were common in the population. Oral habits such as smoking and betelnut chewing were associated with an increase in leukoplakia, which may lead to oral cancer in some people. Dental caries varied in prevalence and severity. Higher decayed, missing and filled teeth scores in the primary teeth of young children were associated with defective tooth formation (hypoplasia) linked to maternal and childhood illnesses and nutritional deficiencies. Older adults had the worst oral health, with the 45-64 year old group having a caries prevalence of 95% and a decayed, missing and filled teeth score of 14.7. Root surface caries, seen as a consequence of poor oral hygiene and gum recession, was the major site of caries attack in the older Hull. The public oral health services are unable to reach a large proportion of the rural population, and people continue to use traditional herbal and folk remedies. Many seek the skills of local tooth extractors who use six-inch nails with no anaesthetic.     

Echocardiogram‐gated multislice spiral CT in functionally univentricular heart following long‐lasting Waterston–Cooley anastomosis

Waterston–Cooley anastomosis may be carried out in patients with tricuspid atresia to provide pulmonary perfusion. It is associated with several complications, including preferential blood flow to the right lung, hypoplasia of the left pulmonary artery, obstruction of the anatomosis or rupture of pulmonary aneurysms. We study a patient with thrombosis in the pulmonary arteries following surgical construction of a Waterston shunt in childhood. Imaging findings and clinical symptoms are discussed with emphasis on echocardiogram‐gated multislice spiral CT.