Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study

Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged  65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m²/d days 2–5 + AraC 1 g/m²/12 h days 1–5, with (Q⁺) or without (Q⁻) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/25 (52%) patients in the Q⁺ group achieved CR, compared to 3/17 (18%) patients in the Q⁻ group ( P  = 0.02) and median Kaplan-Meier survival was 13 months in the Q⁺ group, and 8 months in the Q⁻ group ( P  = 0.01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy.     

Reaching rural Africans with eye care services: findings from primary eye care approaches in Rubavu District,Rwanda

Objective Assessment of a primary eye care programme in rural Rwanda over 2 years, with the aim of providing evidence to guide the development, training, supervision, or monitoring of primary eye care in Africa. Method A comprehensive eye care programme in Rubavu District including a surgical service, health promotion, diagnostic and treatment services, training of health centre nurses and village health workers, and periodic visits by eye professionals to the health centres was implemented. Monitoring systems put in place from the beginning of the programme facilitated assessment of service use over 2 years. Results A total of 6495 people received eye care services at eight health centres (3912 from nurses and 2583 from visiting eye professionals) and 149 Rubavu residents had surgery for cataract. Increases in service use in the first few months were not maintained over the 2‐year period. The number of patients receiving surgery for cataract was less than half of the number referred for surgery. Conclusion In this setting, initial increases in use of services at health centres were not maintained. Reasons varied and included the observation that VHW tend to refer patients to health centres only when there was a visiting eye professional. Reductions in visits to health centres could also be traced to changing government policies on medicines provided through insurance coverage. Increasing rates of referral and uptake of cataract surgery will require revising programme activities and adopting additional strategies.     

The big bang of hemofiltration: the beginning of a new era in the third millennium for extra-corporeal blood purification!

Since the last decade, hemofiltration and especially high volume hemofiltration has rapidly evolved from a somewhat experimental treatment towards a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine resistant hypodynamic septic shock. Nevertheless, this approach lacks prospective randomized studies (PRT'S) evaluating the critical role of early hemofiltration in sepsis. An important step forward which could be called the 'big bang' in term of hemofiltration was the publication of a PRT in patients with acute renal failure (ARF) (1). Before this study (2), nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. So the world of hemofiltration in ICU is not a definitive world, it is still in expansion. Indeed, we now have to try to define what will be the exact dose we need in septic acute renal failure. This dose might well be 'higher' than 35 ml/kg/hour in the septic acute renal failure 'group' as suggested by many studies (2-5). At present, it is the issue of continuous dose of high volume hemofiltration that has to be tested in future randomized studies. Since the Vicenza study (2) has shown that 35 ml/kg/h is the best dose in terms of survival, dealing with non septic acute renal failure in ICU, several studies from different groups have shown that, in septic acute renal failure, a higher dose might correlate with better survival. This has also been shown in some way by the study of the 'Vicenza group' but not with a statistically significant value (2). New PRT'S have just started in Europe like the IVOIRE study (hIgh VOlume in Intensive caRE) (6) and the RENAL study. Another large study is looking more basically at dose in non septic acute renal failure in Australasia and is led by the group of Rinaldo Bellomo in Melbourne (7) as well as the ATN study (8) led by Palevsky and colleagues in the USA, also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' like early goal directed therapy (9) has to be studied in our critical ill patients. Regarding this issue, fewer studies, mainly retrospective exist, but again the IVOIRE study (6) will address this issue by studying septic patients with acute renal injury according to the Rifle classification (10). So, this review focuses on the early application and on the adequate dose of continuous high volume hemofiltration in septic shock in order to improve not only hemodynamics, but survival in this very severely ill cohort of patients. This could well be called the 'big bang of hemofiltration' as one could never have anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of ICU-septic acute renal failure patients. On top of the use of early and adequate dose of hemofiltration in sepsis, a higher dose could also provide better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this paper also reviews 'brand' new theories regarding the rationale for hemofiltration in sepsis. Finally, this paper also addresses the so-called negative studies as well anticipated side effects.     

The brain in the early fossil jawless vertebrates: evolutionary information from an empty nutshell

Various 535-365 million year-old extinct jawless vertebrates taxa provide either direct or indirect information about brain and cranial nerve morphology. The paraphyletic group referred to as "ostracoderms", includes some forms in which the braincase closely encapsulated the brain, thereby providing relatively accurate data about its overall external morphology. Current morphology-based phylogenies suggests that "ostracoderms" are in fact jawless stem gnathostomes, and the closely similar aspect of their brain cavity suggests that it illustrates the ancestral condition of the gnathostome brain and fills the morphological gap between the brain condition of the extant cyclostomes and that of the extant jawed vertebrates.     

Efficacy of different regimens of adjuvant radiochemotherapy for treatment of glioblastoma

AIMS AND BACKGROUND: We retrospectively analyzed the impact of different adjuvant chemotherapy regimens in a group of patients treated for glioblastoma compared to patients receiving only postoperative radiotherapy. MATERIAL AND METHODS: Eighty-six consecutive patients underwent radiotherapy between January 2000 and December 2003: 52 patients received radiotherapy alone, 17 patients radiochemotherapy with low-dose temozolomide (20 mg/m(2)) + cyclooxygenase-2-inhibitors (200 mg), 6 patients radiochemotherapy with high-dose temozolomide (50 mg/m2). Eleven patients, with unfavorable prognostic factors, were treated with imatinib and 55/2.5 Gy. RESULTS: The groups treated with high- and low-dose temozolomide showed the longest overall survival (median, 21 months and 17 months, respectively). Median overall survival was 9 months for radiation alone and 4 months for the imatinib-treated group. The same positive trend of temozolomide on prolonged overall survival was confirmed when only patients submitted to maximally radical resection or patients with KPS >70 were considered. Differences in progression-free survival were not statistically significant. CONCLUSIONS: Patients treated with adjuvant temozolomide either inside or outside of study protocols had survival times similar to other reports or randomized studies. The absence of a significant influence of temozolomide on progression-free survival could depend on the unavoidable drawbacks and biases of retrospective investigations or on the definition of relapse used. The unsatisfactory results of radiotherapy plus imatinib may have been due to a high prevalence of unfavorable prognostic factors in the respective patients. The ongoing controlled trial will further define the efficacy of adjuvant/concomitant imatinib.