The economic payoffs of integrated malaria control in the Zambian copperbelt between 1930 and 1950

It has long been suggested that malaria is delaying the economic development of countries that are most severely affected by the disease. Several studies have documented the economic consequences of malaria at the household level, primarily in communities engaged in subsistence farming. A missing element is the appraisal of the economic impact of malaria on the industrial and service sectors that will probably become the backbone of many developing economies. We estimate the economic effects of integrated malaria control implemented during the colonial period and sustained for 20 years in four copper mining communities of the former Northern Rhodesia (now Zambia). Integrated malaria control was characterized by strong emphasis on environmental management, while part of the mining communities also benefited from rapid diagnosis and treatment and the use of bednets. The programmes were highly successful as an estimated 14,122 deaths, 517,284 malaria attacks and 942,347 work shift losses were averted. Overall, 127,226 disability adjusted life years (DALYs) were averted per 3-year incremental period. The cumulative costs of malaria control interventions were 11,169,472 US dollars (in 1995 US dollars). Because the control programmes were so effective, the mining companies attracted a large reservoir of migrant labourers and sustained healthy work forces. The programmes averted an estimated 796,622 US dollars in direct treatment costs and 5,678,745 US dollars in indirect costs as a result of reduced work absenteeism. Within a few years of programme initiation, Northern Rhodesia became the leading copper producer in Africa, and mining generated the dominant share of national income. Copper production and revenues, which increased dramatically during malaria control interventions, amounted to the equivalent of 7.1 billion US dollars (in 1995 US dollars). Integrated malaria control in copper mining communities was a sound investment. It had payoff for public and occupational health, generally, and without it copper extraction and social and economic development would have been impossible.     

Gastrointestinal side effects in children with Wilson’s disease treated with zinc sulphate

AIM:To investigate the side effects of a zinc sulphate therapy in a cohort of Polish pediatric patients with Wilson’s disease. METHODS:We retrospectively analyzed a cohort of 53 pediatric patients with Wilson’s disease treated at the Children’s Memorial Health Institute in Warsaw, Poland between the years 1996 and 2011 with zinc sulphate. Patients were diagnosed with Wilson’s disease according to the scoring system of Ferenci, with 49 cases confirmed by mutation analysis. Data about the dosage scheme of zinc sulphate, side effects and efficacy and toxicity of the treatment were collected and recorded in the patient’s medical chart at each visit to the hospital. RESULTS:Mean age of diagnosis for the entire cohort was 10 years (range, 2.5-17 years). Duration of treatment with zinc sulfate was 83.3 wk (range, 8-344 wk). Side effects, all of gastrointestinal origin, were observed in 21 patients (40% 9 males and 12 females), irrespective of the duration of therapy. Thirteen out of 21 patients were over the age of 10 years. The most common ATP7B mutation was p.H1069Q. Esophagogastroduodenoscopy, performed in 7 patients (33.3%) suffering from persistent and severe abdominal pain, revealed gastrointestinal ulcerations or erosions with negative Helicobacter pylori tests in all subjects investigated. The above mentioned 7 patients were treated with proton pump inhibitors. Three of those experienced resolution of symptoms, whereas proton-pump inhibitors failed to alleviate symptoms of the remaining four children and conversion of therapy to D-penicillamine was needed. CONCLUSION:Zinc sulphate appears to cause significant gastrointestinal side effects, which children on therapy for Wilson’s disease should be closely monitored for.     

Effect of concomitant use of pentoxifylline and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer

We evaluated the effects of pentoxifylline (PTX) and alpha-tocopherol on the clinical outcome of 66 patients with stage IIIB non-small cell lung cancer in a randomized clinical trial. All patients received 46 Gy of external radiotherapy to the primary tumor and regional lymph, nodes with an additional 14-Gy dose to the primary tumor. Thirty-three of the 66 patients also received PTX (400 mg, three times daily) and alpha-tocopherol (300 mg, twide daily) during radiotherapy, followed by 400 mg of PTX and 300 mg of alpha-tocopherol daily for 3 mo after radiotherapy. The remaining 33 patients (control group) received radiotherapy only. After a mean follow-up time of 12 mo, 18 patients remained alive. During follow-up, there were local recurrences in 14 patients and distant metastases in 18 patients. In patients who received PXT and alpha-tocopherol, 1- and 2-yr overall survival rates were 55% and 30%, respectively, and median survival was 18 mo. In control patients, 1- and 2-yr overall survival rates were 40% and 14%, respectively, with a median survival of 10 mo. These differences were statistically significant (p=0.0175). In patients who received PXT and alpha-tocopherol, progression-free survival rates for 1 and 2 yr were 48% and 23%, respectively; median survival was 12 mo. In the control group, the corresponding rates were 24% and 18%; median survival was 8 mo (p=0.0223). We conclude that the use of PTX and alpha-tocopherol combined with radiotherapy offers a possible survival advantage in this patient population.     

Characteristics and Analysis of Risk Factors for Mortality in Infective Endocarditis

Objective: The aim of our study was to establish the etiology of and risk factors for infective endocarditis (IE) and determine the prognostic factors for adverse outcome during hospital admission in a Turkish population. Material and Methods: Between January 2002 and January 2004, the clinical and laboratory features of 112 consecutive adult patients (>18 years) with diagnosis of IE who were referred to the infectious diseases clinics/departments of 17 teaching hospitals in Turkey were evaluated. Cases of IE were defined according to the modified Duke Criteria. Mortality was defined as death occurring within 30 days or during hospital stay period. Univariate and multivariate analyses were performed to predict the factors related to fatal outcome. Results: A total of 112 consecutive patients presented with 101 definite and 11 probable IE episodes were defined according to the modified Duke Criteria. The mean age was 45.2±19.9. Fifty percent of the patients were male. Ninety (60.4%) of the 112 patients had risk factors for IE and 48 (42.9%) of them had ≥2 risk factors. On the other hand, 49.1% of patients had cardiac risk factors. Blood cultures were positive in 94 (83.9%) cases. Staphylococci were the most common agents (50.0%), followed by streptococci (28.7%) and enterococi (16.0%). Native cardiac valves were detected in 93 (83%) of the episodes of suspected IE. Valvular involvement was present in 103 (92%) patients; the mitral valve, alone or in combination with other valves, was affected in 70 (62.5%) of the patients. Echocardiography detected vegetations in 105 patients (93.8%). The mortality rate was 28.6%. Three factors were independently associated with mortality: haemodialysis OR: 14.5 (95% CI: 1.5–138.2), mobile vegetation OR: 4.8 (95% CI: 1.5–15.4) and mental alteration OR: 4.1 (95% CI: 1.1–15.6). Conclusion: Mortality is still high in IE. Our data indicate that patients with altered mental status, mobile vegetation, or on haemodialysis had poorer prognosis. Atahan Cagatay, Istanbul University Istanbul Medical School, Turkey; Funda Ergin, Baskent University, Medical School, Turkey; Hurrem Bodur, Ankara Numune Hospital, Turkey; Gulsen Ozkaya Sahin, Hacettepe University, Medical School, Turkey; Irfan Sencan, Abant Izzet Baysal University, Duzce Medical School, Turkey; Saban Gurcan, Trakya University, Medical School, Turkey; Elif Doyuk, Osmangazi University, Medical School, Turkey; Bilgiul Mete, Istanbul University Cerrahpasa, Medical School Turkey; Oral Oncul, Gulhane Academy, Medical School, Turkey     

Endometriotic umbilical port site metastasis after laparoscopy

We present the case of a 40-year-old woman who had been previously operated for endometrioma 2 years ago by laparoscopy, with the complaint of an umbilical mass with cyclical pain pattern. The dark-colored mass was excised and pathology report revealed it to be an endometriotic implant.     

beta-Tubulin mutations are associated with resistance to 2-methoxyestradiol in MDA-MB-435 cancer cells

2-Methoxyestradiol is an estradiol metabolite with significant antiproliferative and antiangiogenic activity independent of estrogen receptor status. To identify a molecular basis for acquired 2-methoxyestradiol resistance, we generated a stable 2-methoxyestradiol-resistant (2ME2R) MDA-MB-435 human cancer cell line by stepwise exposure to increasing 2-methoxyestradiol concentrations. 2ME2R cells maintained in the presence of the drug and W435 cells maintained in the absence of the drug showed 32.34- to 40.07-fold resistance to 2-methoxyestradiol. Cross-resistance was observed to Vinca alkaloids, including vincristine, vinorelbine, and vinblastine (4.29- to 6.40-fold), but minimal resistance was seen to colchicine-binding agents including colchicine, colcemid, and AVE8062A (1.72- to 2.86-fold). No resistance was observed to paclitaxel and epothilone B, polymerizing agents (0.89- to 1.14-fold). Genomic sequencing identified two different heterozygous point mutations in the class I (M40) isotype of beta-tubulin at amino acids 197 (Dbeta197N) and 350 (Kbeta350N) in 2ME2R cells. Tandem mass spectrometry confirmed the presence of both wild-type and the mutant beta-tubulin in 2ME2R cells at the protein level. Consistently, treatment of parental P435 cells with 2-methoxyestradiol resulted in a dose-dependent depolymerization of microtubules, whereas 2ME2R cells remained unaffected. In contrast, paclitaxel affected both cell lines. In the absence of 2-methoxyestradiol, 2ME2R cells were characterized by an elevated level of detyrosination. Upon 2-methoxyestradiol treatment, levels of acetylated and detyrosinated tubulins decreased in P435 cells, while remaining constant in 2ME2R cells. These results, together with our structure-based modeling, show a tight correlation between the antitubulin and antiproliferative effects of 2-methoxyestradiol, consistent with acquired tubulin mutations contributing to 2-methoxyestradiol resistance.     

Primary squamous cell carcinoma of the stomach: a case report

Squamous cell carcinoma (SCC) originating from the stomach is a relatively rare entity. There are theories regarding the development of this rare tumor, but its exact pathogenesis remains obscure. Fewer than 100 cases of primary SCC of the stomach have been presented in the literature. Due to the advanced stage at the time of diagnosis in most of these cases, the prognosis is generally poor. In the case presented here, dissemination of the tumor to the transverse colon, gallbladder and omentum was present at diagnosis. Despite the tumor's advanced stage, complete remission was achieved after six courses of adjuvant chemotherapy with 5-flourouracil and cisplatin. No recurrence has been detected during follow-up. The patient has been healthy with no sign of the disease for three years.     

Cytarabine-induced fever complicating the clinical course of leukemia

The aim of this study is to assess the frequency and clinical characteristics of cytosine arabinoside-induced fever in patients with acute myeloid leukemia in remission, receiving high-dose (3 g/m2) consolidation therapy. We have investigated 77 consolidation cycles over a study period of 4 years. A strict definition of cytosine arabinoside-induced fever (i.e. patients without neutropenia and with negative blood cultures during the fever episodes) was used. Of the 77 consolidation cycles, fever due to cytarabine was detected in 33 cycles (43%). Median time of onset of fever from the beginning of first chemotherapy dose was 22 h and maximum temperature was in the range 38.0-39.7 degrees C (mean+/-SD: 38.8+/-0.5 degrees C). Median duration of fever was 10.15 h and did not exceed 72 h. There was no difference with regard to neutrophil and white blood cell counts between cycles with or without cytarabine fever. The cost of investigation of fever source was about US$2137. Our analysis suggests that 'cytarabine fever' is a frequent and often a self-limiting complication of high-dose cytosine arabinoside consolidation therapy, and cost-reductive approaches could be structured based on this background.