Radiologic emphysema morphology is associated with outcome after surgical lung volume reduction

BACKGROUND: Lung volume reduction surgery is known to alleviate dyspnea and to improve pulmonary function, performance in daily activity, and quality of life in selected patients with severe pulmonary emphysema. We investigated the role of radiologically assessed emphysema morphology on functional outcome after a lung volume reduction operation. METHODS: The preoperative chest computed tomograms in 50 consecutive patients who had undergone surgical lung volume reduction were retrospectively reviewed by 6 physicians blinded to the clinical outcome. Emphysema morphology was determined according to a simplified classification (ie, homogeneous, moderately heterogeneous, and markedly heterogeneous; lobe predominance). We studied the impact of these morphologic aspects on functional outcome at 3 months. RESULTS: We found a fair interobserver agreement applying our classification system. Functional improvement after surgical lung volume reduction was best in markedly heterogeneous emphysema with an increase in forced expiratory volume in 1 second of 81% +/- 17% (mean +/- standard error, n = 17) compared with 44% +/- 10% (n = 16) for intermediately heterogeneous emphysema. But also in patients with homogeneous emphysema clinical relevant improvement of function could be observed (increase in forced expiratory volume in 1 second = 34% +/- 6%; n = 17). CONCLUSIONS: The morphologic type of emphysema, assessed by a simplified surgically oriented classification, is an important predictor of surgical outcome. Lung volume reduction surgery may also improve dyspnea and lung function in homogeneous emphysema.     

Improving breastfeeding support: a community health improvement project

BACKGROUND: Because of the brevity of the postpartum hospital stay, mothers and their newborns are discharged home before breastfeeding is well established. In 1992, feedback from patients who had given birth at Fletcher Allen Health Care (Burlington, VT) suggested a need for more consistent, expert, and timely assistance with breastfeeding in the hospital and better continuity of care during the first few weeks at home. QUALITY IMPROVEMENT TEAM: In 1993 a team developed objectives, analyzed the problem and possible solutions, and made eight recommendations on how the hospital could do more to promote breastfeeding. Implementation by team members and hospital staff included policy development, staff education, acquisition of funding, a visiting professorship, development of a lactation consultant coordinator and team, and patient surveys to evaluate the program. A late 1994 survey of 63 postpartum patients on their day of discharge indicated a high level of satisfaction with breastfeeding support in the hospital. CURRENT STATUS: Activities are being undertaken for lactation consultation coverage, further policy development, implementation of nurse competency validation, improved patient and family education materials, and continued evaluation of the breastfeeding support program through patient surveys. CONCLUSION: In the face of barriers such as the project's large scope, a paucity of internal team members, and a large number and variety of recommendations, some of the recommendations and follow-up plans have yet to be implemented. Yet the project has yielded improvements in care and provides a model of how hospitals can expand their traditional boundaries of care and quality improvement into community health issues.     

In vitro toxicity of methyl mercury to fathead minnow cells

We have reported previously that serotonin (5-HT) stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs) through active transport of 5-HT and cellular signaling that includes elevation of superoxide (O2.-) and enhancement of protein tyrosine phosphorylation. Ginkgo biloba extract 501 (EGb 501), which has been demonstrated to act as an antioxidant, was found to block both the elevated O2.- and the proliferative and hypertrophic influences of 5-HT on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxidase or the stimulation of phosphorylation of GTPase-activating protein (GAP). A similar effect of Ginkgo biloba extract 501 occurred on Chinese hamster lung fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has been associated with mitogenesis. We conclude from these studies that Ginkgo biloba extract 501 quenches O2.- formation by 5-HT, thereby blocking its mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT appears to precede the elevation of O2.-.     

Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study

BACKGROUND/AIMS: Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary biliary cirrhosis, although the effect is modest. Since primary biliary cirrhosis has many features of an autoimmune disorder, immunosuppressives added to ursodeoxycholic acid may be of value in the treatment of primary biliary cirrhosis. METHODS: A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary biliary cirrhosis, who had already been treated with ursodeoxycholic acid for at least 1 year, but had not achieved complete disease remission. Patients were randomized to additional prednisone (30 mg per day initially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronate and calcium. The principal aim of the study was to assess the short-term benefits and risks of the combined bile acid and low-dose immunosuppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry, liver histology, bone mass and the occurrence of adverse events. RESULTS: Pruritus (p=0.02), alkaline phosphatase, aspartate aminotransferase, IgM and procollagen-III-propeptide improved significantly (all p<0.002) in the combined treatment group as compared to the placebo group. Histological scores for disease activity and disease stage decreased significantly within the combination treatment group (p<0.001). CONCLUSIONS: In patients with primary biliary cirrhosis receiving ursodeoxycholic acid, there is an additional beneficial effect of 1-year treatment with prednisone and azathioprine on symptoms and biochemical, fibrogenetic and histological parameters. These results strongly encourage the evaluation of this triple treatment regimen in long-term controlled trials of adequate size to document its effect on clinical events.     

Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27

Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q ( CCM1 ). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease.     

Serum- and bradykinin-induced calcium transients in familial Alzheimer's fibroblasts

The calcium-sensitive photoprotein, aequorin, was used to examine serum- and bradykinin-induced transient increases in free cytosolic calcium ions in skin fibroblasts from 10 individuals with early onset familial AD (FAD), including four who were biopsied before their clinical symptoms would allow a diagnosis of AD, 2 individuals with late onset FAD, 8 at-risk but nonsymptomatic individuals, and 13 controls. The data show that (a) among controls, the peaks of the calcium transients increase in height as a function of donor age; (b) transients induced by 10% serum, 10 nM bradykinin (BK) or 100 nM BK were generally lower in FAD fibroblasts, including those from donors in the early stages of the disease, than in age-matched control cells; (c) such transients are reduced in cells from a proportion of the nonsymptomatic, at-risk individuals. Thus, serum- and BK-induced calcium transients are reduced in fibroblasts from both early and more advanced stage FAD donors and perhaps even from donors who are presymptomatic carriers of the defective gene. The data also suggest that changes in calcium transients in FAD fibroblasts neither mimic nor exaggerate the effects of normal aging.     

Lithium protection against oxygen toxicity in rats: ammonia and amino acid metabolism

1. The use of Li pre-treatment in rats before high pressure oxygen exposure has been reported effective in controlling convulsions. This is an effect which is better demonstrated if exposure to oxygen follows shortly after Li injection than exposure following several hours later. 2. This study has investigated the hypothesis that the protective action of Li may be exerted, in the short term, by its removing ammonia from the blood and alleviating the latter's known toxic action. 3. A normal Li distribution time profile in unstressed rat brain and blood following intraperitoneal injection has been established. Brain and blood ammonia, amino acids and Li concentrations were also measured in Li-treated animals exposed and convulsed by oxygen. These measurements were made both shortly (15 min) and also several hours after (24 hr) Li treatment. Ammonia and amino acid values in Li-protected groups were compared to normal unstressed animal values and also to values in animals convulsed by oxygen unprotected by Li pre-treatment. 4. In rat brain abd blood significant (P less than 0-001) elevation of ammonia and glutamine and depression of gamma-amino butyric acid (brain only) and glutamate was noted following oxygen treatment in unprotected animals. Prior injection of Li 15 min before high pressure oxygen exposure delayed convulsions twice as long. Additionally if these animals were only exposed to oxygen for a period of time equal to that which would normally produce convulsions in unprotected animals, brain and blood ammonia and amino acids were maintained near to unstressed animal levels. Concomitantly, blood Li concentrations were considerably depressed below the values one would expect from the previously determined Li distribution time profile. 5. In rats exposed to high pressure oxygen 24 hr after Li treatment there was no protective action against high pressure oxygen convulsion, rather a potentiating effect for convulsion was seen. 6. These data present compelling evidence for the controlling effect of Li in rats, on rising blood ammonia concentration which occurs in high pressure oxygen exposure. The effect might well be due to the known chelating properties of Li with ammonia.     

M.O.S. neural pulse modulator

Through control of the substrate-source voltage of the input transistor, output pulses can be controlled and modulated in an m.o.s. neural line.     

Physician reluctance to discuss advance directives. An empiric investigation of potential barriers

BACKGROUND: To determine the relative impact of five proposed barriers to physician usage of advance directives with the aim of increasing the number of advance directives generated. METHODS: Questionnaires were sent to 460 internal medicine resident and attending physicians at a large New York, NY, hospital. Of these, 277 (60%) responded. We used multiple regression to measure the impact of five barriers to physician-initiated discussions of advance directives (time constraints, compensation concerns, discomfort with the subject, beliefs about appropriateness, and lack of understanding) on respondents' estimates of the number of advance directives held by respondents' patients, the number of recent advance directive discussions, and the number of discussions initiated by physicians. RESULTS: Physician lack of understanding and erroneous beliefs about appropriateness had particularly strong effects, serving as barriers to recent advance directive discussions (P < .0001 and P < .0001, respectively) and total number of advance directives held (P < .0001 and P < .02). Physicians' lack of knowledge also served as a barrier to the percentage of discussions that were physician initiated (P < .003 and P < .04). Time constraints and lack of comfort affected only discussions that were physician initiated (P < .001). Compensation concerns did not appear to serve as a barrier. Respondents were supportive of the concept of advance directives but reported minimal use of them in appropriate situations. CONCLUSIONS: Attention can now be focused on methods to overcome the five barriers studied and thereby enhance the execution of advance directives.