BACKGROUND AND PURPOSE: The impact of second surgery and overall predictors of outcome following GBM recurrence remains controversial, with few definitive studies published to date. This study sought to identify major predictors of survival after second surgery. METHODS: We collected clinical, pathological and radiographic data through a retrospective review of patient charts. All patients underwent elective surgery for GBM recurrence at our institution in the past 6 years. Kaplan Meier, with log-rank test and Breslow test, was applied to determine and compare significance of dichotomized variables on survival time. The Mann Whitney U non-parametric test was used to determine whether the median survival time differed significantly between groups, for the various clinical factors investigated. RESULTS: Among variables examined, age, less than 50 (P = 0.04) was significant. Patients younger than 50, had a median survival period of 11.8 months, while patients, age 50 or older, survived a median time of 4.2 months. Additionally, our data supports that the palliative effects of second surgery may be complemented by adjuvant therapy as a second round of chemotherapy may prolong survival. Though chemotherapy after reoperation was not found to be statistically significant in extending survival time using the Kaplan-Meier test (P = 0.08), the median survival time was found to be significantly higher in patients that received chemotherapy after reoperation, compared with those who did not, using the Mann Whitney U test (P = 0.05). Patients who underwent chemotherapy after second resection survived a median of 10.6 months. Comparatively, median survival time of patients who did not undergo chemotherapy was 3.9 months. CONCLUSION: These results confirm that patient age (<50) is an important predictor of increased survival after second surgery. Additionally, our data supports that if second surgery will decrease performance status and prevent the administration of further chemotherapy postoperatively, the benefits of re-resection are limited.
Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01) after AQ + SP or AQ + AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p< 0.003). Conclusion AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http://www.controlled-trials.com/isrctn/trial/|/0/67520427.html).
The efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Africa is increasingly compromised by development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequences coding for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) is known to confer resistance to pyrimethamine and sulfadoxine. This study investigated the occurrence of these mutations in infected blood samples taken from Ugandan children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of mutations in DHFR and DHPS that were significantly selected under S/P pressure at day 7: a combination of alleles 51-isoleucine and 108-asparagine in DHFR, and 436-serine, 437-alanine, 540-lysine and 581-alanine in DHPS, appears to play a major role in the development of in vivo resistance in P. falciparum strains against S/P. Therefore, earlier results derived from isolates from hyperendemic areas in Tanzania were confirmed by this investigation.
SUMMARY Polymerase chain reaction (PCR) combined with non-radioactive DNA hybridization was applied for the detection and characterization of a 150 bp tandem repeat of Onchocerca volvulus . DNA of worms from western Uganda was amplified and then probed with a digoxygenin-labelled oligonucleotide, specific for the forest form of O. volvulus and compared to samples from various African countries. Hybridization was only observed with PCR products from the forest in Liberia, south-eastern Ghana, Benin and southern Cameroon, but not with worms from Uganda or the savannah in Burkina Faso and northern Ghana. A nested PCR using primers derived form the forest form-specific DNA sequence confirmed these results. Morphometric studies revealed length differences between the microfilariae of Ugandan O. volvulus to those of West Africa, especially to those of the savannah in Burkina Faso. It is concluded that the forest/savannah classification of O. volvulus from West Africa is not suitable for Simulium weasel -transmitted O. volvulus from Uganda.
The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.
Summary The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.
Summary The efficacy of chloroquine in the treatment of uncomplicated falciparum malaria in Africa is heavily compromised by high levels of drug resistance. The occurrence of active site mutations in the Plasmodium falciparum multi drug resistance‐gene 1 ( pfmdr1 ) has been associated with development of resistance to chloroquine. This study investigates the occurrence of several mutations at codons 86, 1042 and 1246 of the pfmdr1 ‐gene in infected blood samples taken from Ugandan children before treatment with chloroquine and their relationship to clinical and parasitological resistance. Even though a clear association of CQR to one certain pfmdr1 single point mutation could not be substantiated, the frequency of resistance was consistently higher for samples revealing any of the mutations than among wild type samples, and 90% of the clinically resistant samples did present a mutation. Thus detection of these allelic pfmdr1 polymorphisms is not a decisive factor for prediction of clinical chloroquine resistance, but an interplay of the different mutations with unknown cofactors is to be assumed and the possible role of other genetic alterations remains to be investigated.
Journal Article Resistance in vivo of Plasmodium falciparum to co-trimoxazole in western Uganda Get access A.H.D. Kilian, A.H.D. Kilian 1GTZ Basic Health Services Western Uganda, Fort Portal, Uganda2Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany Address for correspondence: Albert Kilian, GTZ, P. O. Box 27, Fort Portal, Uganda; phone/fax +256 483 22743. Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Jelinek, T. Jelinek 1GTZ Basic Health Services Western Uganda, Fort Portal, Uganda Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Prislin, I. Prislin 2Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Kabagambe, G. Kabagambe 3District Health Services, Kabarole District, Uganda Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Byamukama, W. Byamukama 3District Health Services, Kabarole District, Uganda Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Mpigika, G. Mpigika 4Ministry of Health, Entebbe, Uganda Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Korte, R. Korte 5GTZ Division for Health, Population and Nutrition, Eschborn, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar F. von Sonnenburg F. von Sonnenburg 2Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 92, Issue 2, March-April 1998, Pages 197–200, https://doi.org/10.1016/S0035-9203(98)90748-9 Published: 01 April 1998 Article history Received: 19 August 1997 Revision received: 10 November 1997 Accepted: 11 November 1997 Published: 01 April 1998
The prevalence of the apathogenic filaria Mansonella perstans was studied in four parishes in western Uganda as part of an onchocerciasis control programme to avoid futile treatment. Blood samples from 1543 persons aged over 14 years from 19 villages were examined for the presence of microfilariae using a modified Knott method. The prevalence of microfilaraemic persons ranged between the parishes from 39% (95% CI 35.9-42.0%) to 81% (95% CI 76.2-84.8%). With exception of single microfilariae of Onchocerca volvulus no other filaria species was detected. Onchocerciasis mass treatment campaigns did not reduce the prevalence of M. perstans infection, since 6-12 months after treatment with a single dose of 150 micrograms/kg ivermectin the prevalence in 124 persons was about the same as before treatment. The QBC-fluorescence technique was employed for the detection of microfilariae in samples from outpatients of the government hospital in Fort Portal: in 16% of 120 children and 24% of 369 adults microfilariae of M. perstans were detected.
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