Brain edema after human cerebral hemorrhage: a magnetic resonance imaging volumetric analysis

Although perihematoma brain edema can significantly modify neurologic outcome after intracerebral hemorrhage (ICH), our knowledge of its natural history is incomplete. We report on the correlation between hematoma (HV) and edema volumes (EV) in 14 patients with ICH during the first week after the ictus using MRI volumetric analysis. We conducted a retrospective MRI volumetric analysis of intraparenchymal hematomas and surrounding perihematoma brain edema in 14 patients with ICH. The mean age was 54.4 years (range 32-71 years). The time from symptom onset to MRI was 3.5 days (range 1-6) days, and the etiology of ICH was as follows: hypertension (70%), arteriovenous malformation rupture (19%), and postpallidotomy (11%). The mean HV was 15 mL (range 0.9-67.4 mL), and the mean EV was 17.3 mL (range 2.8-50.6 mL). Using linear regression analysis, we demonstrated EV to be significantly and directly related to HV: (EV) = 7.68 + 0.64(HV); r = 0.8; P = 0.001. In conclusion, we report significant and direct correlation between the HV and EV within the first week after ICH. The clinical implications of this observation, if confirmed, will help to better design clinical trials in ICH research as well as to better allocate adequate clinical resources in high-risk subgroups of patients with ICH.     

Soy isoflavones in the treatment of prostate cancer

Epidemiological studies suggest an inverse association between soy intake and prostate cancer (Pca) risk. We have previously observed that soy isoflavone genistein induces apoptosis and inhibits growth of both androgen-sensitive and androgen-independent Pca cells in vitro. To determine the clinical effects of soy isoflavones on Pca we conducted a pilot study in patients with Pca who had rising serum prostate-specific antigen (PSA) levels. Patients with Pca were enrolled in the study if they had either newly diagnosed and untreated disease under watchful waiting with rising PSA (group I) or had increasing serum PSA following local therapy (group II) or while receiving hormone therapy (group III). The study intervention consisted of 100 mg of soy isoflavone (Novasoy) taken by mouth twice daily for a minimum of 3 or maximum of 6 mo. Forty-one patients were enrolled (4 in group I, 18 in group II, and 19 in group III) and had a median PSA level of 13.3 ng/ml. Thirty-nine patients could be assessed for response. Soy isoflavone supplementation was given for a median of 5.5 (range 0.8-6) mo per patient. Although there were no sustained decreases in PSA qualifying for a complete or partial response, stabilization of the PSA occurred in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. There was a decrease in the rate of the rise of serum PSA in the whole group (P = 0.01) with rates of rise decreasing from 14 to 6% in group II (P = 0.21) and from 31 to 9% in group III (P = 0.05) following the soy isoflavone intervention. Serum genistein and daidzein levels increased during supplementation from 0.11 to 0.65 microM (P = 0.00002) and from 0.11 to 0.51 microM (P = 0.00001), respectively. No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU. These data suggest that soy isoflavones may benefit some patients with Pca.     

Evaluation of glargine group-start sessions in patients with type 2 diabetes as a strategy to deliver the service

Improving glycaemic control in patients with type 2 diabetes reduces microvascular complications. The national service framework for diabetes and the new general medical service contract have been aiming to direct more focus on improving HbA1c. These measures have resulted in increasing number of patients being initiated on insulin therapy, which increases the workload of diabetes specialist nurses (DSNs). Initiating insulin on a one-to-one basis is time consuming. As a result DSN-led insulin group-start sessions were introduced. To evaluate DSN-led glargine group-start and self-titration as a strategy of providing service. We assessed the impact of this method on the use of DSNs time, HbA1c and on patients' satisfaction. A prospective audit in a district general hospital. Groups of 5-7 patients received two 2-h sessions at weeks 0 and 2. During these sessions, patients were initiated on insulin glargine and received an educational package and a self-titration protocol. DSNs did not see patients after week 2. Patients were able to phone the DSNs for advice till the end of the titration period. Patients completed Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline, week 2 and 12 months. Weight and HbA1c were assessed at base line and 12 months later. Twenty-nine consecutive patients were included. Baseline HbA1c improved at 6 months and remained stable at 12 months (medians 10.0, 8.7 and 8.9 respectively, p < 0.001). DTSQ score improved between week 0 and 2 and this was maintained at 12 months (medians 26, 35 and 34 respectively, p < 0.001). After week 2, the DSNs spent a median of 21 min advising patients by phone during the titration period. Weight did not increase significantly. In our centre, DSN-led insulin group-start sessions and self-titration improved glycaemic control. Patients were satisfied with this method of starting insulin. This was achieved with minimal DSNs time and input and proved to be effective, yet less time consuming.     

The atrophy and changes in the cellular compositions of the thymus and spleen observed in mice subjected to short-term exposure to perfluorooctanesulfonate are high-dose phenomena mediated in part by peroxisome proliferator-activated receptor-alpha (PPARα)

We have previously shown that short-term, high-dose exposure of mice to the environmentally persistent perfluorooctanoate (PFOA) results in thymic and splenic atrophy and the attenuation of specific humoral immune responses. Here we characterize the effects of a 10-day treatment with different dietary doses (1–0.001%, w/w) of perfluorooctanesulfonate (PFOS), a similar fluorochemical, on the immune system of male C57BL/6 mice. At doses greater than 0.02%, PFOS induced clinical signs of toxicity in the animals, whereas at the concentration of 0.02%, this compound caused weight loss, hepatomegaly and atrophy of the thymus, spleen and adipose tissue without toxicity. With this latter dose, histopathological and flow-cytometric analysis revealed that (i) the thymic cortex was virtually depleted of cells; (ii) the total numbers of thymocytes and splenocytes were reduced by 84 and 43%, respectively; (iii) although all populations of thymocytes and splenocytes were smaller, the thymic CD4⁺CD8⁺ cells and the splenic B-lymphocytes were most decreased. These alterations resembled those evoked by analogous exposure to PFOA, but were less pronounced. At lower doses (less than 0.02%), PFOS induced hepatomegaly without affecting the thymus or spleen. Finally, comparison of male wild-type 129/Sv mice and the corresponding knock-outs lacking peroxisome proliferator-activated receptor-alpha (PPARα) indicated that these effects of PFOS are not strain-dependent. More importantly, hepatomegaly is independent of PPARα, the thymic changes are partially dependent on this receptor, and splenic responses are largely eliminated in its absence. Thus, immunomodulation caused by PFOS is a high-dose phenomenon partially dependent on PPARα.     

Increased risk of oral cancer in relation to common Indian mitochondrial polymorphisms and Autosomal GSTP1 locus

BACKGROUND: Polymorphisms at mitochondrial (mt) loci could modulate the risk of diseases including cancers. Here the mtDNA polymorphisms at 12,308 nucleotide pairs (np), 11,467 np, 10,400 np, and 10,398 np were studied to examine the association with the risk of oral cancer and leukoplakia, alone and in combination with polymorphisms at the GST loci. METHODS: Polymorphisms at mt loci were screened in 310 cancer, 224 leukoplakia, and 389 control individuals by polymerase chain reaction (PCR) restriction length polymorphism (RFLP) and most of the GST genotype data were taken from previously published reports. Data were analyzed to determine the risk of the diseases. RESULTS: The major allele, A, at 12,308 np on tRNA(Leu) (CUN), increased the risk of cancer (odd ratio [OR] of 1.7; 95% confidence interval [95% CI], 1.1-2.6) but not that of leukoplakia. The same allele also appeared to increase the risk of cancer in smokers (OR of 4.0; 95% CI, 1.1-14.4), who are mostly males (OR of 1.8; 95% CI, 1.1-3-2), but not in smokeless tobacco users, who are mostly females. The major allele A at 11467 np demonstrated identical results as the major allele, A, at 12,308 np. The major alleles G at 10,398 np and T at 10,400 np (ie, M-haplogroup) increased the risk of cancer significantly in smokers (OR of 2.6; 95% CI, 1.2-5.7 and OR of 2.4; 95% CI, 1.1-5.1, respectively). The risk-risk genotype-allele combination at GSTP1 and mt12308 np loci increased the risk of cancer (OR of 2.6; 95% CI, 1.4-4.9) when compared with the nonrisk-nonrisk combination in leukoplakia patients. CONCLUSIONS: Polymorphisms at the mt loci alone and in combination with the risk genotype at GSTP1 increased the risk of oral cancer. Thus, risk genotypes from 2 different organelles may work in combination to increase the risk of oral cancer.     

Polymorphisms at XPD and XRCC1 DNA repair loci and increased risk of oral leukoplakia and cancer among NAT2 slow acetylators

Polymorphisms at N-acetyl transferase 2 locus (NAT2) lead to slow, intermediate and rapid acetylation properties of the enzyme. Improper acetylation of heterocyclic and aromatic amines, present in tobacco, might cause DNA adduct formation. Generally, DNA repair enzymes remove these adduct to escape malignancy. But, tobacco users carrying susceptible NAT2 and DNA repair loci might be at risk of oral leukoplakia and cancer. In this study, 389 controls, 224 leukoplakia and 310 cancer patients were genotyped at 5 polymorphic sites on NAT2 and 3 polymorphic sites on each of XRCC1 and XPD loci by PCR-RFLP method to determine the risk of the diseases. None of the SNPs on these loci independently could modify the risk of the diseases in overall population but variant genotype (Gln/Gln) at codon 399 on XRCC1 and major genotype (Lys/Lys) at codon 751 on XPD were associated with increased risk of leukoplakia and cancer among slow acetylators, respectively (OR = 4.2, 95% CI = 1.2-15.0; OR = 1.6, 95% CI = 1.1-2.3, respectively). Variant genotype (Asn/Asn) at codon 312 on XPD was also associated with increased risk of cancer among rapid and intermediate acetylators (OR = 1.9, 95% CI = 1.2-2.9). Variant C-G-A haplotype at XRCC1 was associated with increased risk of leukoplakia (OR = 1.7, 95% CI = 1.2-2.4) but leukoplakia and cancer in mixed tobacco users (OR = 3.1, 95% CI = 1.4-7.1, OR = 2.4, 95% CI = 1.1-5.4, respectively) among slow acetylators. Although none of the 3 loci could modulate the risk of the diseases independently but 2 loci in combination, working in 2 different biochemical pathways, could do so in these patient populations.     

Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution

BACKGROUND: Variations in genetic mutations in pancreatic carcinoma between different geographical regions have not been studied extensively, especially in developing countries where pancreatic cancer is relatively rare. METHODS: We studied the molecular pathology of 54 pancreatic adenocarcinomas from Egyptian patients residing in a heavily polluted region of the eastern Nile River delta and compared the findings with 45 tumors from patients residing in low-pollution regions. RESULTS: Rates of K-ras mutation in codon 12 and of p53 mutation in exons 5-8 were higher in tumors of patients from the high-pollution region as compared with the low-pollution regions (61.5 versus 34.2%, respectively, for K-ras, P = 0.01; 25.9 versus 11.6%, respectively, for p53, P = 0.08). There were also distinct differences in the specific types of K-ras and p53 mutations between the two regions. The ratio of G-to-T k-ras transversion mutation (codon 12) relative to wild-type was significantly higher in tumors from the high-pollution region (0.90) than tumors from the non-pollution site (0.28) (P = 0.03). Relative to tumors with wild-type, the ratio of p53 mutations in exons 5, 7 or 8 to wild-type in tumors from the high-pollution region was significantly higher than the ratio from the non-pollution site (0.28 versus 0.03, P = 0.01). Logistic regression showed that G-to-T transversion mutation in K-ras was predicted by the region of residence of the patients. CONCLUSIONS: Our study reveals that there are differences in the frequencies and types of K-ras and p53 mutations found in pancreatic adenocarcinomas of patients in high-pollution and low-pollution regions in Egypt and suggests that environmental factors may explain these differences. We speculate that gene-environment interactions in pancreatic carcinogenesis also occur in other populations.