Clinical research and trials in developing countries

Over 80 per cent of the global disease burden occurs in developing countries. Yet the proportion of research conducted in these countries is less than 10 per cent of the global research activity. This article emphasizes the need to conduct research in developing countries on locally relevant questions, provides general principles that may assist in establishing such studies, and describes some experiences in the cardiovascular area.     

Clinically significant blunt cardiac trauma: role of serum troponin levels combined with electrocardiographic findings

BACKGROUND: The true importance of blunt cardiac trauma (BCT) is related to the cardiac complications arising from it. Diagnostic tests that can predict accurately if such complications will develop or not may allow early and aggressive monitoring or early discharge. We investigated the role of two simple and convenient tests, serum cardiac troponin I (cTnI) and electrocardiogram (ECG), when used to identify patients at risk of cardiac complications after BCT. METHODS: Over a 10-month period, 115 patients with evidence of significant blunt thoracic trauma were prospectively followed to identify the presence of clinically significant BCT (Sig-BCT), defined as cardiogenic shock, arrhythmias requiring treatment, or structural cardiac abnormalities directly related to the cardiac trauma. An ECG was obtained at admission and at 8 hours. Cardiac troponin I was measured at admission, at 4 hours, and at 8 hours. Transthoracic echocardiography was performed when clinically indicated. The sensitivity, specificity, and positive and negative predictive values of ECG and cTnI to identify Sig-BCT were calculated. Clinical risk factors for Sig-BCT were examined by univariate and multivariate analysis. RESULTS: Nineteen patients (16.5%) were diagnosed with Sig-BCT and, in 18 of them, symptoms presented within 24 hours of admission. Abnormal electrocardiographic findings were detected in 58 patients (50%) and elevated cTnI levels in 27 (23.5%). Electrocardiography and cTnI had positive predictive values of 28% and 48% and negative predictive values of 95% and 93%, respectively. However, when both tests were abnormal (positive) or normal (negative), the positive and negative predictive values increased to 62% and 100%, respectively. Other independent risk factors for Sig-BCT were head injury, spinal injury, history of preexisting cardiac disease, and a chest Abbreviated Injury Score greater than 2. CONCLUSION: The combination of ECG and cTnI identifies reliably the presence or absence of Sig-BCT. Patients with an abnormal ECG and cTnI need close monitoring for at least 24 hours. Patients with a normal admission ECG and cTnI can be safely discharged in the absence of other injuries.     

Promotion of NCI-Black-Reiter male rat bladder carcinogenesis by dimethylarsinic acid an organic arsenic compound.

Dimethylarsinic acid (DMAA) is a major metabolite of inorganic arsenicals in mammals. In the present study, we investigated its promoting effects on urinary bladder carcinogenesis in NCI-Black-Reiter (NBR) rats, which lack alpha2u-globulin synthesizing ability. Male 9-14-week-old NBR rats were treated sequentially with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 4 weeks and then given 100 ppm DMAA in their drinking water (group 1) for 32 weeks. Induction of preneoplastic lesions (papillary or nodular hyperplasia) in this DMAA-treated group was significantly increased as compared to the carcinogen alone control group (P < 0.01). The development of carcinomas was also enhanced and a significant increase in the 5-bromo-2'-deoxyuridine (BrdU) labeling index of the urinary bladder epithelial cells was observed for the DMAA treatment group. These results indicate that DMAA has promoting effects on urinary bladder carcinogenesis even in NBR rats, so its effects are not dependent on the presence of alpha2u-globulin.     

Augmentation of natural killer cell activity in vivo against tumour cells by some wild plants from Jordan

Twelve aqueous extracts prepared from Jordanian plants that are currently used in traditional medicine to treat various types of cancer were tested in mice for their augmentation of natural killer cells in vivo in generating cytotoxicity against YAC tumour targets. After 1 week of oral administration of aqueous extracts of fresh Nigella sativum (N.s.) seeds and Allium sativum (A.s.) bulbs significant augmentation of splenic natural killer (NK) cells (62.3% +/- 6.4% and 52.6% +/-5.4% cytotoxicity, respectively), was obtained in comparison with spontaneous activity (24.5% +/- 1.6%) at 200:1 effector:target ratio. Onopordum acanthium (O.a.) stem and leaves and Allium cepa (A.c.) bulbs showed intermediate augmentation (38.6% +/- 3.8% and 30.6% +/- 3.4% cytotoxicity, respectively) while the rest showed insignificant augmentation activity. The fresh aqueous extract of a mixture of the plants with high and intermediate activity showed little insignificant augmentation activity (72.7% +/- 6.7% cytotoxicity) of NK cells compared with that obtained with each plant alone.     

Tunneled epidural catheter infections in noncancer pain: increased risk in patients with neuropathic pain/complex regional pain syndrome

BACKGROUND AND OBJECTIVE: Tunneled epidural catheters are often used to control pain and facilitate rehabilitation in patients with regional pain syndromes. A cohort retrospective study design was undertaken to evaluate the risk of catheter-related infection in patients who underwent a TEC placement to manage their chronic noncancer regional pain over a 5-year period. METHODS: There were 260 tunneled epidural catheters placed in 218 patients accounting for a total of 10,985 catheter-days. Of these, 230 catheters were placed in patients with neuropathic pain (90% of whom had complex regional pain syndrome) and 30 catheters in patients with somatic pain. RESULTS: There were 24 epidural space infections in symptomatic patients, 23 of whom were in the neuropathic pain group-22 had complex regional pain syndrome. Additionally, tunneled epidural catheters had to be discontinued in 34 patients because of superficial infection or suspicion of infection; 33 of these were in the neuropathic pain group. The differences in the infection rates were significantly higher in the neuropathic pain group compared to the somatic group. When analyzed to an infection index per 1,000 catheter-days, the rate of infection rate was 5.51 for the patients with neuropathic pain and 2.43 for the patients with somatic pain. The rates for deep and superficial infections were 2.26 and 3.25, respectively, per 1000 catheter-days for the neuropathic pain group compared to 1.22 for both deep and superficial infections in the patients with somatic pain. There were 6 frank epidural abscesses upon contrast-enhanced magnetic resonance imaging examinations of the spine, 1 epidural phlegmon and 2 patients displayed mild or questionable epidural enhancement on magnetic resonance imaging, suggestive of epidural inflammation. All these magnetic resonance imaging abnormalities were detected in patients with complex regional pain syndrome. Two of the patients with epidural abscesses underwent surgical exploration and drainage of the epidural abscess, though no neurologic deficits were observed in any of the patients. CONCLUSIONS: The higher risk of tunneled epidural catheter infection observed in patients with neuropathic pain (particularly complex regional pain syndrome) warrants further study.     

Nephrectomy versus renal repair after trauma to the kidney: preserve or sacrifice?

The objective of this retrospective study (1992-2003) is to evaluate the effect of nephrectomy in postoperative renal dysfunction. NEPHRECTOMY patients had their kidneys removed and REPAIR patients repaired or only partially resected. All patients were matched 1:1 with controls according to age, Injury Severity Score, Abdominal Abbreviated Injury Score, and mechanism of injury. Outcomes measured were renal dysfunction (serum creatinine > 2 mg/dl for > 2 consecutive days), renal dialysis, length of hospital stay, and mortality. Of 214 patients, 149 were NEPHRECTOMY and 65 REPAIR. Compared to their controls, NEPHRECTOMY and REPAIR patients had a higher rate of renal dysfunction. However, the rate was not different between NEPHRECTOMY and REPAIR. Multivariate analysis found no independent effect of the choice of operation in the development of renal dysfunction. No differences were found in the remaining outcomes measured. We conclude that although renal injury is associated with postoperative renal dysfunction, the type of operation is not. Nephrectomy can be offered when necessary without concerns about increasing the likelihood of postoperative renal failure.