Effects of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice

The present study was designed to investigate the effect of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice. Mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0) and were treated daily with oral administration of various doses of rolipram from days 0 to 20. On day 21, production of anti-OVA IgG and proliferative responses to the antigen were determined. Anti-OVA IgG2a and interferon-gamma (IFN-gamma), as indicators of Th1 responses, and anti-OVA IgG1 and interleukin-10 (IL-10), as indicators of Th2 responses, were also measured. The results showed that treatment with rolipram failed to affect the production of OVA-specific IgG but decreased the proliferation of spleen cells to the antigen. Its inhibitory effect on these immune responses was correlated with a marked decrease in IFN-gamma but not IL-10 production, although neither anti-OVA IgG2a nor IgG1 production was affected by rolipram. These results suggest that rolipram may preferentially inhibit Th1 responses more effectively than Th2 responses. Administration of rolipram resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of joint inflammation by rolipram was associated with the inhibition of the OVA-specific proliferative responses of spleen cells and IFN-gamma secretion. These results indicate that rolipram may be effective in regulating Th1-mediated diseases such as rheumatoid arthritis.     

Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c,Bax, Bid,and caspases

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid). At the same time, tBid became detectable in the mitochondrial fraction, and concomitantly, Bax was found translocated to mitochondria. However, AAP failed to activate the execution caspases 3 and 7 as evidenced by a lack of procaspase processing and the absence of an increase in caspase-3-like activity. In contrast, the administration of the pan-inhibitor of caspases, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (but not its analogue benzyloxycarbonyl-Phe-Ala-fluoromethylketone) prevented the development of liver injury by AAP and the appearance of apoptotic parenchymal cells. This correlated with the inhibition of the processing of Bid to tBid. The caspase inhibitor failed to prevent both the redistribution of Bax to the mitochondria and the loss of cytochrome c. In conclusion, apoptosis is an important causal event in the initiation of the hepatic injury inflicted by AAP. However, as suggested by the lack of activation of the main execution caspases, apoptosis is not properly executed and degenerates into necrosis.     

The use of selective bronchography in predicting reversal of neoplastic obstructive atelectasis

OBJECTIVES: To assess the ability of selective bronchography to predict which patients with neoplastic postobstructive atelectasis will respond to interventional therapies directed at the reexpansion of the affected lung. Furthermore, to compare the utility of selective bronchography with the current predictive standard that reversal of postobstructive atelectasis is unlikely when it is > or = 4 weeks in duration (ie, the 4-week rule). DESIGN: A prospective observational study. SETTING: A tertiary care referral center/medical school. PATIENTS: Twenty-seven consecutive patients with advanced lung cancer or other malignancy, with documented neoplastic postobstructive atelectasis involving a total of 44 lobes. INTERVENTIONS: Lobar collapse was documented radiographically. The duration of atelectasis was investigated and quantified as accurately as possible. Prior to the use of interventional therapies, selective bronchography was performed on each collapsed lobe, and the results were documented. Bronchography results did not influence the decision to proceed with interventional therapies. Patients had each of their collapsed lobes manipulated by interventional techniques that were directed at reexpansion of the lung. One week after the patient underwent the intervention, the degree of reexpansion was assessed radiographically. RESULTS: Interventional therapies leading to significant reversal of airway narrowing were completed in all 44 lobes. These were successful in reexpanding 28 of 44 collapsed lobes (64%). Selective bronchography demonstrated the following two distinct patterns: an intact bronchial tree (ie, tree pattern); or the absence of a distinguishable, distal bronchial tree (ie, blush pattern). The sensitivity of selective bronchography to predict reexpansion is 1.00 (95% confidence interval [CI], 0.90 to 1.00), and its specificity is 0.56 (95% CI, 0.30 to 0.80). There were no complications attributable to selective bronchography. The sensitivity of the 4-week rule to predict reexpansion is 0.61 (95% CI, 0.41 to 0.78), and its specificity is 0.75 (95% CI, 0.48 to 0.93). The results of selective bronchography and use of the 4-week rule were significantly different in predicting which lobes would reexpand and which would not (p = 0.0026). Using selective bronchography to predict the reversal of lobar atelectasis, the positive predictive value of the tree pattern was 0.80 and the negative predictive value of the blush pattern was 1.00. The values for the 4-week rule are 0.81 and 0.52, respectively. CONCLUSIONS: Selective bronchography is a useful tool for predicting whether patients with neoplastic postobstructive atelectasis would benefit from interventional techniques that are directed at lobar reexpansion. Selective bronchography appears to be superior to the 4-week rule in this regard.     

Diffuse alveolar hemorrhages and hemorrhagic pleural effusion after thrombolytic therapy with streptokinase for acute myocardial infarction

Thrombolytic therapy with streptokinase is commonly used in acute myocardial infarction and has markedly reduced morbidity and mortality from this condition. However, it can cause various hemorrhagic and immunological complications. We report a patient who developed diffuse pulmonary hemorrhages and bilateral hemorrhagic pleural effusion after thrombolytic therapy with streptokinase for acute myocardial infarction. This was recognized by a drop of hematocrit, pulmonary infiltrates, hemorrhagic pleural effusion and hypoxemia. The diagnosis was confirmed by demonstration of iron-laden macrophages (siderophages) in bronchoalveolar lavage. The patient required mechanical ventilation and recovered successfully. This combination of pulmonary hemorrhages and hemorrhagic pleural effusion following streptokinase therapy is extremely unusual and has not been reported previously.     

Adolescent nutrition in a rural community in Bangladesh

The objective of this study was to assess the nutritional status of adolescent boys and girls in a rural community in Bangladesh. Between December 1996 and January 1997, a cross-sectional survey was carried out in 803 households, each containing at least one adolescent, sampled consecutively from four purposely-selected villages in Rupganj Thana, Narayanganj district. Initially, the guardians of 1483 healthy and unmarried 10–17 year old adolescents (51% boys and 49% giris) were interviewed about family structure and socio-economic status. Out of these children, 906 (47% boys and 53% girls) from 597 households were weighed, had their height and MUAC measured and were clinically examined. Blood was then collected from 861 adolescents for haemoglobin estimation. The median monthly income per person in these 597 families was approximately Taka 554 (US $12). Twenty seven per cent of the household heads were labourers, 21% were solvent farmers, 14% ran small scale businesses and 6% were unemployed. Sixty seven per cent of adolescents were thin (defined as BMI < 5th centile of WHO recommended reference) with 75% boys and 59% girls being affected. The percentage of thin adolescents fell from 95% at age 10 years to 12 % at age 17 years. The prevalence of stunting (height for age < 3rd centile NCHS/WHO) was 48% for both boys and girls and rose from 34% at age 10 to 65% at age 17. On clinical examination angular stomatitis was present in 46%, 27% nad glossitis, 38% had pallor, 11% ha’d dental caries, 3.2% had an conspicuously enlarged thyroid and 2.1% had eye changes of vitamin A deficiency. According to INACG (International Nutritional Anaemia Consultative Group, 1985) cut-off values, 94% of the boys and 98% of the girls were anaemic. We conclude that rural Bangladesh adolescents suffer from high rates of malnutrition and almost universal anaemia. Nutritional interventions to target this population are urgently required.     

Comparing the efficacy of team based learning strategies in a problem based learning curriculum

We introduced two variants of team based learning (TBL) strategies in pathology course to seek their efficacy in a problem based learning (PBL) curriculum. The TBL strategy was adopted in two different sessions. One during regular resource session (RS‐TBL) and other during a weekly review session (RVS‐TBL) of the PBL curriculum. The study involved 104 second year students during their 8 weeks of cardiovascular‐respiratory units and 3 weeks of hematology units. RS‐TBL was adopted for cardiovascular‐respiratory unit and RVS‐TBL for hematology unit. The first 8 weeks of the course were implemented as RS‐TBL and the last 3 weeks as RVS‐TBL. The results showed that the group performance was markedly improved than individual performance in both RS‐TBL and RVS‐TBL (p < 0.001). Comparison between the RS‐TBL and RVS‐TBL revealed that individual student and group performance was better in the RVS‐BL (p < 0.001). The result of the student attitudinal survey indicated an 88% agreement that TBL enhanced their understanding of pathology concepts and critical analysis. Most of the participants (85%) found RVS‐TBL to be more useful. Post‐TBL, end of semester examination results proved beneficial for the students in risk. The study demonstrated that RVS‐TBL may be preferably adopted to enhance the philosophy of TBL in a PBL curriculum.     

Breast Cancer Knowledge and Related Behaviors among Women in Abha City, Southwestern Saudi Arabia

Breast cancer is the most common malignancy among women in Saudi Arabia. A cross-sectional study was conducted on 1,092 women attending urban primary health care centers in Abha City southwestern Saudi Arabia about breast cancer knowledge, attitudes, and related practices. Only 22.0 % heard about mammography, and 41.5 % heard about breast self-examination (BSE). More than half of the women in the study identified changes occurring in case of breast cancer and identified risk factors. Only 8.3 % were examined by clinical breast examination (CBE), 6.2 % were examined by mammography, and 29.7 % performed BSE. The study points to the insufficient knowledge of women and the low practice of BSE, CBE, and mammography. Public awareness should be enhanced by all available means including mass media, schools, social gatherings, and waiting areas in primary health care centers. There is an urgent need for continuing medical education programs for health care workers in the region concerning breast cancer.