Transtracheal high frequency jet ventilation and iatrogenic injury

Editor—We read with interest the article by Bourgain andcolleagues,¹ who reported an 8.4% incidence of subcutaneousemphysema and 1% incidence of pneumothoraces with jet ventilationvia the transtracheal route. Transtracheal catheter placementis an extremely useful technique for patients with significantglottic pathologies such as obstructing glottic tumours, andcan be lifesaving. We do, however, have concerns over its usein     

Inhibitory Activity of Green and Black Tea in a Free Radical-generating System Using 2-Amino-3-methylimidazo[4,5-f]quinoline as Substrate

Green tea and black tea inhibit colon carcinogenesis in rats exposed to the cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In the present investigation, green tea, black tea and (-)-epigallocatechin gallate (EGCG) were shown to block the production of oxygen free radicals derived from IQ in the presence of NADPH-cytochrome P450 reductase. In kinetic studies using IQ as tbe substrate and DMPO as a free radical spin trap, EGCG increased the Km of the reaction without altering Vmax, suggesting competitive enzyme inhibition (Ki=9.% mUM). This was confirmed in spectrophotometric studies using cytochrome c as the substrate, in which EGCG acted as a competitive inhibitor of NADPH-cytochrome P450 reductase (Ki=9.7 μM). These results suggest that the inhibitory activities of green tea and black tea in electron spin resonance assays using IQ as the substrate for the rednctase are related to an indirect effect on the enzyme rather than via direct scavenging of the free radicals. The possible implications of these findings are discussed in the context of pathways involved in the activation and detoxification of IQ in the colon.     

The Influence of Donor and Reservoir Additives on Caco-2 Permeability and Secretory Transport of HIV Protease Inhibitors and Other Lipophilic Compounds

Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors and other lipophilic compounds, and to compare cyclic urea HIV protease inhibitors with marketed compounds. Methods. Absorptive and secretory Caco-2 membrane permeation studies were performed with HIV protease inhibitors and various reference compounds, examining the effects of adding the solubilizing agents dimethylacetamide (DMAC) and albumin in donor and reservoir compartments, respectively. Results. DMAC was useful as an additive in the donor vehicles, increasing the dissolved concentrations of poorly water-soluble HIV protease inhibitors, and enabling more reliable determination of P_app values. Donor vehicles containing up to 5% DMAC could be used without altering Caco-2 barrier function, as indicated by the lack of effect on permeabilities of reference compounds with diverse absorption characteristics. The utilization of a reservoir containing albumin resulted in marked increases in absorptive P_app values for some HIV protease inhibitors as well as other lipophilic, highly protein bound compounds, consistent with albumin increasing the release of these compounds from the cell monolayer. Conclusions. Poorly soluble, lipophilic, highly bound compounds may require using solubilizing agents in the donor and reservoir compartments of Caco-2 permeation experiments for estimating in vivo absorption potential. If the reservoir does not provide adequate sink conditions, cellular retention could over-emphasize the contributions of secretory transport. The cyclic ureas, DMP 450, DMP 850, and DMP 851, have Caco-2 permeabilities suggestive of moderate-to-high oral absorption potential in humans.     

Hb Leiden-beta (0) thalassemia in a Chinese with severe hemolytic anemia

The first case of Hb Leiden (alpha2beta2 6 or 7 Glu---O)-beta (0) thalassemia in a young patient with chronic severe hemolytic anemia, which improved after splenectomy, is described. His parents were Chinese. The patient's blood showed no Hb A or normal beta chains when no blood transfusion was given. His mother was heterozygous for beta(0) thalassemia, and his father and brother had a trait for the unstable Hb Leiden. The Hb Leiden level of the father was 22.6% and that of the brother was 19.3%. It is probable that the abnormal hemoglobin in this Chinese family resulted from an independent gene mutation, unrelated to the one found in 2 Caucasian families reported earlier.     

Understanding locally advanced breast cancer: what influences a woman's decision to delay treatment?

BACKGROUND: Despite early detection having been identified as a key factor in long-term survival of patients with breast cancer, women with locally advanced breast cancer continued to present at many medical centers. METHODS: Women with locally advanced breast cancer (LABC) (N = 11) and matched controls (N = 11) with Stage I or II breast cancer completed semi-structured interviews and the Hospital Anxiety and Depression Scale, Life Orientation Test, Multidimensional Health Locus of Control Scale, Body Investment Scale, Monitor-Blunter Style Scale, and Religious Coping Scale. Five spouses of the LABC group and eight control partners were similarly assessed. RESULTS: On psychological tests, no significant differences were found between patient groups; however, LABC spouses reported significantly greater active religious surrender (t = 2.37, P = 0.037) and depression (t = 3.54, P = 0.047) than control spouses. The women's semi-structured interviews identified that LABC was associated with inattention to routine breast cancer screening, denial, fatalism and reliance on alternative therapies. Spouses of the LABC group tended to be more passive in their wives' medical care, and also utilized fatalistic thinking and denial. CONCLUSIONS: It is important for health care providers to identify patients who will require extra encouragement to seek timely medical care and to follow through with treatment recommendations.     

Physical activity and decreased risk of clinical gallstone disease among post-menopausal women

BACKGROUND: Physical activity may play a role in preventing gallstone disease. METHODS: The activity/gallstone relationship was examined in post-menopausal women from the Study of Osteoporotic Fractures (SOF; 1986-1988), a prospective study of fracture risk factors in 8010 women (mean age = 71.1 years, SD = 4.9). RESULTS: Multivariate logistic regression indicated women in the lowest two quartiles of physical activity, according to questionnaire, had a 59% {OR = 1.59 (1.11-2.29), P = 0.02} and a 57% higher risk {OR = 1.57 (1.11-2.23), P = 0.01} of developing gallstone disease compared to women in the highest quartile of activity (PTrend = <0.0001). Additionally, this relationship was examined in a cohort of 182 post-menopausal women (mean age 74.2 years, SD = 4.1) who participated in a randomized controlled trial of a walking intervention. Women in the randomized clinical trial in the lowest tertile of physical activity determined by a physical activity monitor had a higher risk of developing gallstone disease than women in the highest tertile of physical activity, 13% {OR-1.13 (1.01-1.28), P = 0.05, PTrend = <0.04}. CONCLUSION: Physical activity appears to be inversely related to the development of gallstone disease in post-menopausal women independent of body mass index.     

The impact of own and spouse's urinary incontinence on depressive symptoms

This study investigated the impact of own and spouse's urinary incontinence on depressive symptoms. Attention was paid to the possibility that gender and caregiving might be important factors in understanding significant effects. We used negative binomial regression to analyze survey data for 9974 middle-aged and older respondents to the Health and Retirement Study in the USA. Results supported the hypothesis that the respondents' own urinary incontinence was associated with depressive symptoms (unadj. IRR = 1.73, 95% CIs = 1.53, 1.95 for men; unadj. IRR = 1.50, 95% CIs = 1.38, 1.63 for women). Controlling sociodemographic and health variables reduced this relationship, but it remained statistically significant for both men and women. Having an incontinent wife put men at greater risk for depressive symptoms (unadj. IRR = 1.13, 95% CIs = 1.02, 1.25), although this relation became nonsignificant with the addition of control variables. No relation between women's depressive symptoms and husbands' (in)continence status was found. Caregiving was not a significant variable in the adjusted analyses, but spouses' depressive symptoms emerged as a significant predictor of the respondents' own depressive symptoms. Health care providers must be sensitive to the emotional impact of urinary incontinence. Our findings also suggest the importance of considering the patient's mental health within a wider context, particularly including the physical and mental health of the patient's spouse.     

Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system

BACKGROUND: Cidofovir and Leflunomide are used empirically in the treatment of BK virus nephropathy. The aim of this study is to quantify the antiviral activity of these drugs. METHODS: BK virus was grown in a cell-culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed using a quantitative polymerase chain reaction assay. RESULTS: The inhibitory concentration, effective concentration, and selectivity index for Leflunomide are 39.7+/-6.9, 11.3+/-2.8, and 3.8+/-0.8 microg/mL, respectively. For Cidofovir, these indices were, respectively, 63.9+/-17.2, 36.3+/-11.7, and 2.3+/-0.8 microg/mL. CONCLUSIONS: The in vitro activity of Cidofovir and Leflunomide is modest, and the selectivity index is low. There is a need to develop more effective and less toxic anti-BK virus drugs for clinical use.