O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯的合成

合成了18个O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯类化合物(Ⅰ_1～18)。初步杀螺试验结果表明,其中5个化合物,即Ⅰ_2,3,7,11,12有明显的杀螺增效作用。     

Acquired immunodeficiency syndrome: a perspective

Infection by the Human T-Lymphotropic Virus Type III (HTLV-III) may lead to the devastating and ultimately fatal disease, acquired immunodeficiency syndrome (AIDS). As the virus is transmitted in similar ways to the hepatitis B virus, concern has developed within the dental profession regarding the possibility of clinicians acquiring AIDS through treatment of infected patients. This paper aims to place the significance of HTLV-III infection to dental practice in perspective.     

Membrane resealing in cultured rat septal neurons after neurite transection: evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly

Neurites of cultured septal neurons were transected with a laser under sterile conditions, and the subsequent membrane resealing was assayed using a dye exclusion method. In agreement with findings in other preparations, Ca2+ enhanced resealing: in normal culture medium the percentage of lesioned neurons that resealed within 20-30 min after transection increased with increasing bath [Ca2+] over the range 10(-7) to 2 x 10(-3) M; about 75% of cells resealed in 2 mM Ca2+. Mn2+ and Sr2+ also enhanced resealing, but Mg2+ inhibited it. The percentage of resealing neurons was sensitive to agents known to alter the stability of cytoskeletal components. Agents that tend to disassemble microtubules and/or neurofilaments (e.g., colchicine, low-ionic-strength media) strongly promoted resealing, whereas treatments that tend to stabilize microtubules (taxol, Mg2+) inhibited resealing. Addition of exogenous proteases (papain, trypsin, or dispase) enhanced resealing, whereas inhibitors of cysteine proteases (including a specific inhibitor of calpain, a Ca-activated neutral protease) strongly inhibited resealing. Calmodulin inhibitors inhibited resealing, consistent with reports that calmodulin facilitates calpain-mediated proteolysis of fodrin, a component of the cortical cytoskeleton. Based on these results, we hypothesize that one of the major mechanisms involved in resealing is activation of endogenous proteases by Ca2+ entry into the injured neurite. The resulting changes in the cellular cytoskeleton might promote fusion and resealing of the cut ends of the plasma membrane by enhancing membrane mobility and/or by removing structures that normally prevent membrane-membrane contact.     

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas

Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.     

An alternative technique for undiverting the sigmoid conduit

A technique for undiverting a colonic conduit of limited capacity and with short ureters is described. The colonic segment of the conduit and an additional segment of small bowel are patched together to form a low pressure cystoplasty of large capacity. This technique incorporates 3 principles that are believed to be important in reconstructing any type of cystoplasty: large capacity, increase in diameter and disruption of the strong circular muscle layer of the bowel by detubularization.     

Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms.

Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series of 20 sporadic breast carcinomas and corresponding blood samples for allelic losses of chromosome 17q using microsatellite length polymorphisms. With these highly informative markers (average heterozygosity, 0.73), we observed frequent deletions of 17q at several loci. We found that D17S250 was deleted in 50% (7 of 14), THRA1 in 79% (11 of 14), D17S579 in 59% (11 of 19), NME1 in 29% (5 of 17), MPO in 36% (4 of 11), and GH in 25% (4 of 16) in the tumor set examined. A common region of deletion was found that was flanked by D17S250 to D15S579. These markers have recently been localized to a 6-cM interval of proximal chromosome 17q in bands 17q11.2-q21 and map within the region of the early-onset familial breast cancer locus, implying that the same gene or genes may be involved in both sporadic and familial breast tumors. Thyroid hormone receptor alpha and retinoic acid receptor alpha are two potential candidate genes in this region.     

Predictors of Repeat Emergency Department Visits by Elders

Objective: To determine which characteristics of older patients who use a hospital ED are associated with repeat visits during the 90 days following the index visit.
Methods: The study was conducted in the ED of a 400-bed university-affiliated acute care community hospital in Montreal. Patients aged ≥75 years who visited the ED between 08:00 and and 16:00 on a convenience sample of days over an 8-week period (July and August 1994) were assessed using a questionnaire, physical and cognitive status instruments, and a functional problem checklist. The hospital's administrative database was used to identify repeat visits during the 90 days following the ED visit. The representativeness of the sample was assessed by analyses of ED visits made by 4,466 persons aged ≥65 years during a 12-month period (September 1993 to August 1994) using the hospital's administrative database.
Results: 256 patients aged ≥75 years visited the ED during the study period and 167 were assessed. Of these, 54 (32%) were admitted to the hospital. Among the 113 patients released from the ED, 27 (24%) made repeat visits during the next 90 days. In univariate analyses, repeat visits were significantly associated with the number of functional problems, cognitive impairment, and previous ED visits. In multiple logistic regression, male gender, living alone, and number of functional problems were independent predictors of repeat visits. In the administrative data analyses, nighttime arrival to the ED for the index visit was significantly associated with repeat visits.
Conclusions: Self-reported risk factors can help to identify a group of elders likely to make repeated ED visits; the development of a screening instrument incorporating questions on these problems and implementation of appropriate interventions might improve these patients' quality of life and reduce the demand for further ED care in this age group.     

The role of cyclic nucleotides in atrial natriuretic peptide-mediated inhibition of aldosterone secretion

Using freshly isolated bovine adrenal glomerulosa cells we examined the inhibitory effect of atrial natriuretic peptide (ANP) on aldosterone secretion stimulated by agonists that use either the Ca2+-phosphoinositide or cAMP messenger system. In a continuous perifusion system, angiotensin II (AII) induces a prompt initial rise in aldosterone secretion, followed by a sustained secretory response. Both phases of secretion are rapidly and independently inhibited by ANP. The role of two cyclic nucleotides, cGMP and cAMP, as mediators of this ANP-induced inhibition was examined. The effect of 8-bromo-cGMP (1-100 microM) or (Bu)2cGMP (1-50 microM) on the AII-stimulated rate of secretion was studied in a perifusion system. Either analog, whether added early or late, maximally inhibited by 20-30% only the late or sustained phase of aldosterone secretion. The effect of ANP on cellular cAMP content was examined in a static incubation system. Although ANP caused a reduction in the cAMP content of cells stimulated with either AII or ACTH, it had little or no effect on the cAMP levels in cells stimulated with carbachol. In AII- and ACTH-stimulated cells, the relationship between reduced cAMP content and reduced secretion was explored. In the AII-stimulated cell inhibited by ANP, simple restoration of cAMP content with forskolin did not restore the secretory rate. Pertussis toxin treatment blocked the inhibitory effect of ANP on cAMP content, but did not block its inhibition of secretion. In the ACTH-stimulated cell, reversal of the ANP-induced reduction of cAMP with forskolin, partially restored the stimulated rate of secretion, although restoration of cAMP with a 10-fold higher dose of ACTH did not restore the stimulated rate of secretion in the presence of ANP. These results imply that both the ANP-induced rise in cGMP and the ANP-induced decrease in cellular cAMP content may contribute to the inhibition of steroidogenesis. However, these inhibitory messages do not induce either the magnitude or the temporal pattern of inhibition induced by ANP. Thus, in the adrenal multiple messenger systems may underlie the action of ANP.