Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: shovel versus hoe

Preferred conformers generated from motuporamine and anthracene-polyamine derivatives provided insight into the shapes associated with polyamine transporter (PAT) recognition and potentially dihydromotuporamine C (4a) bioactivity. Molecular modeling revealed that N(1)-(anthracen-9-ylmethyl)-3,3-triamine (6a), N(1)-(anthracen-9-ylmethyl)-4,4-triamine (6b), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-3,3-triamine (7a), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined by the all-anti polyamine shaft extending above the relatively flat, appended ring system. The hoe geometry was also inferred by the (1)H NMR spectrum of the free amine of 7a (CDCl(3)), which showed a strong shielding effect of the anthracene ring on the chemical shifts associated with the appended polyamine chain. This shielding effect was found to be independent over a broad concentration range of 7a, which also supported an intramolecular phenomenon. The degree of substitution at the N(1)-position seems to be an important determinant of both the molecular shape preferences and biological activity of anthracenylmethyl-polyamine conjugates.     

Effect of Moringa oleifera Lam. root-wood on ethylene glycol induced urolithiasis in rats

In India, drumstick (Moringa oleifera Lam. (Moringaceae)) is commonly used as a phytotherapeutic agent. The effect of oral administration of aqueous and alcoholic extract of Moringa oleifera root-wood on calcium oxalate urolithiasis has been studied in male Wistar albino rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Supplementation with aqueous and alcoholic extract of Moringa oleifera root-wood significantly reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in the kidneys of calculogenic rats was also significantly lowered by curative and preventive treatment using aqueous and alcoholic extracts. The results indicate that the root-wood of Moringa oleifera is endowed with antiurolithiatic activity.     

Working patterns and the quality of training of medical house officers: evaluating the effect of the `new deal'

The `new deal' on junior doctors' hours of work has led to the widespread introduction of working patterns such as full shifts and partial shifts in the United Kingdom. The impact of these changes on the training of medical staff is unclear. The subjects of the current study were 36 pre-registration medical house officers working shift rotas and on-call rotas at a teaching hospital in the north of England. They were studied over a 12-month period using a self-report questionnaire seeking their views on the quality of their training experience and their satisfaction with the in-service training they received. Nursing staff, consultant and medical student opinion was also sought. Partial-shift and full-shift systems led to reduced hours of work when compared to on-call rotas (mean hours: partial shift 65·0; full shift 59·8; on-call 72·7), but they were associated with significantly lower training experience and training satisfaction scores for the house officers than were on-call systems (P < 0·01). Shift systems were unpopular among consultants and medical students but not nursing staff. Despite reducing excessive hours of work, shifts may be detrimental to the training of medical house officers. The further imposition of shift working should be suspended until such time as the impact of new working patterns on the training of medical staff has been determined.     

Hematopoietic cell transplantation comorbidity index predicts transplantation outcomes in pediatric patients

Quantifying the risk of hematopoietic cell transplantation (HCT)-related mortality for pediatric patients is challenging. The HCT-specific comorbidity index (HCT-CI) has been confirmed as a useful tool in adults, but has not yet been validated in children. We conducted a retrospective cohort study of 252 pediatric patients undergoing their first allogeneic HCT between January 2008 and May 2009. Pretransplantation comorbidities were scored prospectively using the HCT-CI. Median age at transplantation was 6 years (range, 0.1-20) and median follow-up was 343 days (range, 110-624). HCT-CI scores were distributed as follows: 0, n=139; 1-2, n=52; and 3+, n=61. The 1-year cumulative incidence of nonrelapse mortality (NRM) increased (10%, 14%, and 28%, respectively; P<.01) and overall survival (OS) decreased (88%, 67%, and 62%, respectively; P<.01) with increasing HCT-CI score. Multivariate analysis showed that compared with score 0, those with scores of 1-2 and 3+ had relative risks of NRM of 1.5 (95% confidence interval, 0.5-4.3, P=.48) and 4.5 (95% confidence interval, 1.7-12.1, P<.01), respectively. These results indicate that the HCT-CI score predicts NRM and OS in pediatric patients undergoing HCT and is a useful tool to assess risk, guide counseling in the pretransplantation setting, and devise innovative therapies for the highest risk groups.     

Sociodemographic factors and utilization of eye care services: is there an association with patients presenting to a tertiary referral hospital in acute angle‐closure?

Background: The aim of this study is to examine the relationship between sociodemographic factors and utilization of eye care services in patients presenting in acute angle‐closure (AAC). Design: A hospital‐based retrospective, case‐control study. Participants: Fifty‐five patients consecutively presenting to the emergency department of the Royal Victorian Eye and Ear Hospital with AAC (cases), and 43 patients consecutively referred to the outpatient department for prophylactic laser peripheral iridotomy (controls) over a 3‐year period. Methods: Standardized telephone questionnaires. Main Outcome Measures: Comparisons were made for sociodemographic factors, utilization of eye care services and provision of information on glaucoma and premonitory symptoms of AAC. Results: No significant differences across a range of socioeconomic and demographic factors were found. Fewer cases reported having attended an eye care professional ever (P = 0.02), or in the 12 months preceding their acute hospital attendance (P = 0.002), and had less awareness of angle closure glaucoma (P = 0.001). Logistic regression modelling demonstrated premonitory symptoms of AAC (odds ratio 3.96, [95% confidence interval 1.52–10.32], P < 0.001) and a period of greater than 12 months since the last eye examination (odds ratio 3.89, [95% confidence interval 1.64–9.21]) were significantly associated with the risk of AAC. Conclusions: No significant differences in socioeconomic or demographic parameters between cases and controls were identified. Control subjects had a history of more frequent and recent access to eye care services than cases. The finding that more than one‐third of patients presenting with AAC had consulted an eye care provider in the preceding year suggests that a significant proportion of individuals at risk of AAC remain undetected.     

Dengue fever related acalculous cholecystitis in a North Indian tertiary care hospital

BACKGROUND AND AIMS: To document the clinical outcome and prognosis of acalculous cholecystitis in dengue fever. METHODS: Prospective analysis of 27 cases of dengue fever presenting to the medical emergency of a tertiary care referral hospital in Chandigarh, India. RESULTS: All patients with dengue fever presenting with abdominal pain in the year 2003 were studied by ultrasound examination for the presence of acalculous cholecystitis. Five cases presented in October and 22 cases in November. Mean age was 29.8 +/- 9.7 years and there were 21 males and six females. Mean duration of fever was 5.07 +/- 1.8 days and mean duration of body ache was 4.06 +/- 2.6 days. The mean platelet counts for all cases at presentation were 29.41 +/- 18.41 x 10(9)/L and at discharge 95.28 +/- 53.01 x 10(9)/L. The mean duration of in-hospital stay was 3.4 +/- 1.7 days. Fourteen patients presented with pain in the abdomen and were confirmed to have acalculous cholecystitis on ultrasound examination of the abdomen (mean gallbladder wall thickness was 5.2 +/- 1.03 mm). Amongst all variables assessed, the only significant difference seen was that the duration of in-hospital stay was 1.68 days more in the group with acalculous cholecystitis. CONCLUSION: Acalculous cholecystitis should be strongly suspected in patients with dengue fever presenting with abdominal pain. Our study has shown that acalculous cholecystitis occurred in 14 out of 27 patients with dengue fever.