Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

CD4 cell counts in adults with newly diagnosed HIV infection in Barbados.

OBJECTIVE: To evaluate the absolute CD4 cell counts of all the newly diagnosed HIV-infected persons who presented at the Ladymeade Reference Unit (LRU), which serves as the national HIV/AIDS referral and treatment center for the country of Barbados. DESIGN AND METHODS: The study group was comprised of HIV-infected adults who had been diagnosed with HIV infection and referred to the LRU between January and December 2002. All the patients referred to the LRU had a CD4 cell count done at their first visit to the unit, as part of the routine workup to assess their disease status and need for antiretroviral therapy. RESULTS: Of the 106 newly diagnosed adults, 62 of them (58.5%) were males, who had a median age at presentation of 40 years; the other 44 of them (41.5%) were females, and their median age at presentation was 36 years. Nearly one-fifth (18.2%) of the females were aged 16-25 years, whereas only 8.1% of the males were in this age group. The majority (57.6%) of the study group were diagnosed because they presented with an HIV/AIDS-related illness. Overall, the median CD4 cell count at the time of diagnosis was 183/microL; 52 of 103 adults (50.5%) with a newly diagnosed HIV infection had a CD4 cell count that was < 200. Among males, the median CD4 cell count was 161/microL, and 32 (53.3%) of 60 males had CD4 cell counts < 200. In contrast, among females, the median CD4 cell count was 223, and 20 (46.5%) of 43 females had a CD4 cell count that was < 200/microL. However, this difference in the proportion of males and females with a CD4 cell count less than 200/microL was not statistically significant (P = 0.63). CONCLUSIONS: At the time of HIV diagnosis, over one-half of the adults had an initial CD4 cell count that was consistent with relatively advanced disease. Proportionally more women than men presented at a younger age, and proportionally more women than men presented in the early stages of the disease. These patterns indicate a clear need for enhanced educational efforts regarding the importance of HIV testing for at-risk individuals across Barbados. This testing could improve efforts to reduce transmission as well as the prognosis for patients who receive antiretroviral therapy.     

PHYSICO-CHEMICAL CHARACTERIZATION OF SEED OIL AND NUTRIENT ASSESSMENT OF ADENANTHERA PAVONINA, L: AN UNDERUTILIZED TROPICAL LEGUME

Analysis showed the seeds of Adenanthera pavonina contained appreciable amounts of proteins (29.44g/100g), crude fat (17.99g/100g), and minerals, comparable to commonly consumed staples. Total sugar was low (8.2g/100g) while starch (41.95g/100g) constitutes the major carbohydrates. Low levels of antinutrients were reported and methionine and cystine were the most deficient amino acids. Linoleic and oleic acids make up 70.7 percent of the total fatty acids. Free fatty acid levels were relatively high but peroxide and saponification values of 29.6mEqkg^-1 and 164.1mgKOHg^-1respectively point to a resemblance to oils processed for food. It was concluded that A. pavonina seeds represent a potential source of oil and protein that could alleviate shortages.     

Cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.     

Neuroprotective strategies in parkinson’s disease: protection against progressive nigral damage induced by free radicals

Brain undergoes neurodegeneration when excess free radicals overwhelm antioxidative defense systems during senescence, head trauma and/or neurotoxic insults. A site-specific accumulation of ferrous citrate-iron complexes in the substantia nigra dopaminergic neurons could lead to exaggerated dopamine turnover, dopamine auto-oxidation, free radical generation, and oxidant stress. Eventually, this iron-catalyzed dopamine auto-oxidation results in the accumulation of neuromelanin, a progressive loss of nigral neurons, and the development of Parkinson's disease when brain dopamine depletion is greater than 80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.-)OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be prevented by antioxidants including selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease. Furthermore, in addition to protection against serum deprivation stress, the induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive oxygen species are unavoidable by-products of iron-catalyzed dopamine auto-oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage, and nigral loss, all of which can be prevented by endogenous and exogenous (.-)NO. Natural and man-made antioxidants can be employed as part of preventative or neuroprotective treatments in Parkinson's disease and perhaps dementia complexes as well. For achieving neuroprotection and neuro-rescue in early clinical parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be more effective than the current treatment with extremely high doses of a single antioxidative agent.     

Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto Rican coasts.

A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects.     

Development of ultrasound-assisted dispersive liquid–liquid microextraction–large volume injection–gas chromatography–tandem mass spectrometry method for determination of pyrethroid metabolites in brain of cypermethrin-treated rats

3-Phenoxybenzoic acid (3-PBA) and 4-hydroxy-3-phenoxybenzoic acid (OH-PBA) are the two common metabolites for most pyrethroid insecticides. A rapid, sensitive, and eco-friendly method has been developed based on ultrasound-assisted dispersive liquid–liquid microextraction (DLLME) coupled to large volume injection–gas chromatography–tandem mass spectrometry for the simultaneous determination of pyrethroid metabolites in rat brain treated with cypermethrin (CYP). Brain samples were homogenized in methanol (disperser solvent) followed by derivatization with methyl chloroformate (MCF) and extraction using DLLME. Factors that influence the extraction and derivatization efficiency such as type and volume of extraction and disperser solvent, sonication time, pH, ionic strength, and volumes of MCF and pyridine were optimized. Under optimized conditions, the limits of detection were 1 and 4 ng/g for 3-PBA and OH-PBA, respectively. Mean recoveries of pyrethroid metabolites in rat brain were in the range of 83–95 %. The developed method was successfully applied for determination of 3-PBA and OH-PBA in brain samples of CYP-treated rats. The developed method can be adopted for rapid and sensitive analysis of pyrethroid metabolites in toxicological and forensic laboratories.     

A Qualitative Study on the Food Habits and Related Beliefs of Pregnant British Bangladeshis

It is quite challenging to deal with the health care needs of migrant populations in general, especially pregnant women, due to their diverse sociopolitical and cultural beliefs and practices. In this article, we aim to examine and understand the food habits and beliefs of pregnant British Bangladeshis using qualitative methods. Our results indicate some positive associations between the increased intakes of particular foods to ensure healthy outcomes. We also note that migration affects pregnant Bangladeshi women's physical and mental conditions. We conclude that effective health care and awareness about traditional food beliefs and habits, and their subsequent reflection into the national and local policy agendas, may bring forth positive changes and improve the overall health of pregnant women.