Attributable fraction for cardiac malformations

To the authors' knowledge, attributable fractions for cardiac malformations have not been reported before. The Baltimore-Washington Infant Study published factors associated with several major cardiac malformations in Maryland, the District of Columbia, and adjacent counties of northern Virginia in 1981-1989. For eight of these malformations, the authors provide attributable fractions of those factors that are potentially causal. Summary attributable fractions range from 13.6% (four factors) for hypoplastic left heart to 30.2% (seven factors) for transposition of great arteries with intact ventricular septum. Extra attributable fraction for factor x, defined as summary attributable fraction for all factors minus that for all but x, is largest for: 1) paternal marijuana use in transposition of great arteries with intact ventricular septum, 7.8%; 2) paternal anesthesia in tetralogy of Fallot, 3.6%; 3) painting in atrioventricular septal defect with Down syndrome, 5.1 %; 4) solvent/degreasing agent exposure in hypoplastic left heart, 4.6%; 5) sympathomimetics in coarctation of aorta, 5.8%; 6) pesticide exposure in isolated membranous ventricular septal defect, 5.5%; 7) hair dye in multiple/multiplex membranous ventricular septal defect, 3.3%; and 8) urinary tract infection in atrial septal defect, 6.4%. Percent-of-cases-exposed dominates relative risk in attributable fraction. If these factors are causal, the larger extra attributable fractions suggest the potential for prevention by specific interventions before/during pregnancy.     

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States

PURPOSE: To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. METHODS AND MATERIALS: Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. RESULTS: Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. CONCLUSION: While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.     

Behavioral factors affecting HIV prevention for adolescent and young adult IDUs

Epidemiological and sociobehavioral data regarding HIV-related risk and injection drug use among adolescents and young adults are examined to provide insight and assistance to nurses delivering preventive intervention and community and clinical care. The increase in HIV/AIDS cases among injection drug users (IDUs), adolescents, and African Americans strongly suggests that clinical care providers acquire a better understanding of the sociocultural and behavioral context within which health care is provided. Transition into injection drug use, high-risk injecting and sexual behaviors, sociodemographic differences, and the importance of social networks are discussed. Nurses are encouraged to provide health promotion, disease prevention messages, and health care to IDUs in small nontraditional clinical settings and to seek out the assistance of the IDUs' social network to increase adherence and compliance to complex prevention and therapeutic efforts.     

Pertussis toxin modification of PC12 cells lowers cytoskeletal F-actin and enhances norepinephrine secretion: involvement of protein kinase C and protein phosphatases

In order to understand the modifications of proteins produced by aldehydes of lipid peroxidation, [1-13C]-2(E)-hexenal, [1-13C]-4-oxopentanal, and a mixture of [1-13C]- and [2-13C]-4-hydroxynon-2(E)-enal were synthesized and the reaction of each of the labeled aldehydes with bovine serum albumin was analyzed by 13C NMR spectroscopy. Protein nucleophiles add to the 3-position of hexenal, and the resulting propanal moieties appear to undergo aldol condensation, form imine cross-links with lysyl residues, or lead to pyridinium rings. During the reaction of 4-oxopentanal with the lysyl residues of bovine serum albumin, only 1-alkyl-2-methylpyrrole and a possible intermediate leading to the pyrrole were observed. Hydroxypyrrolidine cross-links such as 25 could not be detected, leaving the pyrrole as the mediator of protein cross-linking. The Michael adducts are the major products in the reaction between 4-hydroxynon-2-enal and proteins. They exist almost exclusively in the cyclic hemiacetal form and do not appear to cross-link through imine formation with lysyl residues. A minor pathway involves the reaction of 4-hydroxynon-2-enal with the lysyl amino groups of protein resulting in 2-pentylpyrrole adducts that may mediate protein cross-linking. The Michael adducts appear not to be the direct source of the pyrrole, but the imine 32 and the enamine 35 are likely intermediates toward the five-membered ring.     

Carbonyl histochemistry in rat reperfusion nerve injury

Free radical mediated, site-specific lipid and protein oxidation has been implicated in the pathophysiology of an ischaemic/reperfusion injury. The aim of the present study was to determine whether carbonyl formation could be detected histochemically in reperfused rat sciatic nerves. We also examined the effects of preischaemic alpha-tocopherol supplementation on carbonyl formation in reperfused nerves. Seven hours of near-complete ischaemia was induced in rat right hindlimb by occlusion of major arteries using microvascular clips. Histochemical detection of carbonyl compounds, applying naphthoic acid hydrazide (NAH) and Fast Blue B (FBB), was undertaken at thigh, knee and calf levels of sciatic, tibial and peroneal nerves. NAH-FBB reactivity was confined to vessels in reperfused nerves. Positively stained epi-, peri- and endoneurial vessels were invariably observed after 2 h of reperfusion at all levels examined. After 24 and 48 h and 7 days of reperfusion, NAH-FBB-positive vessels were more frequently found at knee and calf levels than at the thigh level. Following preischaemic alpha-tocopherol supplementation, no vessels were stained positively with NAH-FBB, except for some epineurial vessels at knee and calf levels after 2 h of reperfusion. Morphometry in endoneurial vessels at the knee level revealed that endothelial cell area in alpha-tocopherol-treated reperfused nerves was significantly less when compared with those in reperfused nerves without alpha-tocopherol. In conclusion, we have demonstrated histochemical evidence of carbonyl formation in vessels, but not with nerve fibres, in ischaemic/reperfused rat sciatic nerves. These abnormalities were prevented with preischaemic supplementation of alpha-tocopherol.     

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

A mycobacterial etiology has been proposed in Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycobacterium tuberculosis and Myco, paratuberculosis in patients with CD (n = 13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates, column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25, CD69), coupled with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 0.95; P < 0.0001) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4+ (T helper) subset. Although up to 15% of CD8+ (suppressor/cytotoxic) cells also became activated, the CD8+ cells did not proliferate subsequently. Cells expressing the alternate gamma delta form of the T cell receptor (TCR gamma delta+) did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specific increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not support a mycobacterial etiopathology of Crohn's disease.     

Descriptive features of gastric ulcers: do endoscopists agree on what they see?

The alkaline single cell gel test (SCG test or comet assay) was used to study the contribution of excision repair activity to the observed DNA effect after mutagen treatment. The cytotoxicity and genotoxicity of UV-irradiation and the chemical mutagens 4-nitroquinoline-1-oxide (4NQO), benzo[a]pyrene (BP) and 7,12-dimethyl-benz[a]anthracene (DMBA) were compared in a normal human cell line (MRC5CV1) and an excision-deficient xeroderma pigmentosum (XP) cell line (XP12ROSV). The XP cells showed increased cell killing after treatment with all mutagens tested, but did not show a clear increase in DNA migration in the comet assay. DNA effects in MRC5 cells were strongly enhanced by the repair inhibitor aphidicolin (APC), while under the same experimental conditions, APC had no effect on the XP cell line. The enhancing effect of APC on DNA migration in MRC5 cells and the lack of effects in XP cells indicate that the induced DNA effects of 4NQO, BP and DMBA in the comet assay mainly represent the activity of an excision repair process.     

The Flp recombinase cleaves Holliday junctions in trans

The Flp site-specific recombinase is encoded by the 2 micrometers plasmid Saccharomyces cerevisiae and is a member of the integrase family of recombinases. Like all members of the integrase family studied, Flp mediates recombination in two steps. First, a pair of strand exchanges creates a Holliday-like intermediate; second, this intermediate is resolved to recombinant products by a second pair of strand exchanges. Evidence derived from experiments using linear substrates indicates that Flp's active site is composed of two Flp protomers. One binds to the Flp recognition target site (FRT site) and activates the scissile phosphodiester bond for cleavage. Another molecule of Flp bound elsewhere in the synaptic complex (in trans) donates the nucleophilic tyrosine that executes cleavage and thereby becomes covalently attached to the 3' phosphoryl group at the cleavage site. It has previously been shown that Flp efficiently resolves synthetic, Holliday-like (chi) structures to linear products. In this paper, we examined whether resolution of chi structures by Flp also occurs via the trans cleavage mechanism. We used in vitro complementation studies of mutant Flp proteins as well as nicked chi structures to show that Flp resolves chi structures by trans cleavage. We propose a model for Flp-mediated recombination that incorporates trans cleavage at both the initial and resolution steps of strand exchange.     

Oculoplastic surgery with a contact Nd:YAG laser silica scalpel. A case report

The purpose of this study was to evaluate the efficacy of local immunosuppression with intraportal administration of cyclosporine (CsA) in liver transplantation. Mongrel dogs weighing 12-18kg were used. Orthotopic liver transplantation was performed, and animals were divided to the following groups. Group I (n = 7): no treatment, group II (n = 7): CsA 5mg/kg/day intermittent iv, group III (n = 5): CsA 3mg/kg/day continuous iv and group IV (n = 8): CsA 3mg/kg/day continuous portal infusion. Immunosuppressive treatments were carried out for two weeks postransplant. Median survival time (MST) of group IV was significantly prolonged (MST = 18 days, range 10-85 days; p < 0.025) compared with group I (7 days, range 6-13), group II (10 days, range 7-16) and group III (7 days, range 6-10). Data of blood chemical analyses showed that hepatic dysfunction was significantly diminished in group IV compared with other groups (p < 0.05). Blood concentration of CsA on the 5th day (mean +/- SEM) was significantly lower in group IV (238 +/- 22ng/ml) than in group III (438 +/- 113ng/ml). Histologic findings showed that rejection reaction was effectively suppressed in group IV, although SG2M% (mean +/- SEM) of peripheral mononuclear cells of group IV (10.6 +/- 3.3%) was equal to that of group III (11.3 +/- 1.7%). In conclusion, local immunosuppression could achieve prominent effect in preventing hepatic graft rejection with limited systemic immunosuppression.