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Biomedical subjects

D Ross

Publications and source records attributed to D Ross.

At least 199 records · Page 11Linked to original sources
PubMed1992

The pulmonary autograft--a permanent aortic valve.

Between 1969 and 1991, 339 patients had an aortic valve replacement with their own living pulmonary valve at the National Heart Hospital, Guy's Hospital and the Harley Street Clinic, London. The longest follow-up is 24 years and cumulative follow-up is 3774 patient-years. No form of anticoagulation was used and there were no emboli. There were 25 hospital deaths (7.4%) but only 1 death since 1976. Late deaths occurred in 38 patients mainly from technical mal-insertion. Bacterial endocarditis occurred in 11 patients. Thirty-eight patients were re-operated upon and account for 15 of the late deaths. Freedom from re-operation was 85% and the actuarial patient survival was 80% at 20 years. There has been no evidence of primary tissue degeneration and explanted valves showed normal cusp cellularity. Accumulating evidence suggests that the cusps not only survive permanently but can grow with the patient making the operation ideal for children.

Adolescent↗
PubMed1992

Intraneural anatomy of the median nerve provides "third web space" donor nerve graft.

To determine the feasibility of using the fascicular group to the third web space as a source of nerve graft material for bridging of median nerve gaps, a study of the intraneural anatomy of the median nerve was carried out in 23 fresh cadaver specimens. The pattern of plexus formation between the third web-space group and the remainder of the median nerve was determined. The average length of the third web-space fascicular group that could be separated from the median nerve proper prior to plexus intermingling was 24.5 cm. Cross-sectional areas of the graft and the remaining nerve were 4.43 mm2 and 13.76 mm2, respectively. The number of nerve fibers in the third web-space group was 4,847 and in the remaining median nerve, 13,486. Between February, 1989 and October, 1991, this technique has been used on 11 patients to provide donor nerve material for nerve gaps of 3 to 6 cm in the median nerve.

Adolescent↗
PubMed1992

Defective synthesis of early region 4 mRNAs during abortive adenovirus infections in monkey cells.

Human adenovirus 2 grows poorly in monkey cells, partly because of defects in late gene expression. Since deletions in early region 4 (E4) cause similar defects in late gene expression, we examined E4 mRNA expression in abortive infections. Processing of E4 mRNAs was defective during abortive infections, most likely at the level of splicing. At early times in productive infections in HeLa cells, the major E4 species produced is a 2-kb mRNA; at late times, a shift occurs so that smaller spliced E4 mRNAs are also produced. In CV-1 cells, a nonpermissive monkey cell line, this shift did not take place and only the 2-kb species was produced at late times, suggesting a defect in E4 mRNA splicing during abortive infections. The adenovirus DNA-binding protein (DBP) was required for normal processing of E4 mRNAs, since a host range mutant (hr602) containing an altered DBP gene showed a normal late E4 mRNA pattern in CV-1 cells; in addition, DBP was required during infections in HeLa cells for late E4 mRNA expression. DBP was not required for production of the late E4 pattern in transient expression assays in HeLa or 293 cells, suggesting that a second factor in addition to the DBP, present during infection but not transfection, modulates E4 mRNA processing.

Adenoviridae Infections↗
PubMed1992

Mitomycin C.

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Animals↗
PubMed1992

Relationship between DT-diaphorase-mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity.

A series of 2,5-bis-substituted 3,6-diaziridinyl-1,4-benzoquinones have been tested for their ability to be reduced by the two-electron NAD(P)H:(quinone acceptor) oxidoreductase [DT-diaphorase (DTD); EC 1.6.99.2]. Symmetrically alkyl-substituted carbamoyl ester analogs of 2,5-ethyl(carboethoxyamino)3,6-diaziridinyl-1,4- benzoquinone [AZQ], 3,6-diaziridinyl-1,4-benzoquinone (DZQ), and its 2,5-dimethyl derivative (MeDZQ) were tested. The rate of reduction by DTD was DZQ greater than MeDZQ greater than n-butyl- (D5) greater than sec-butyl- (D7) greater than n-propyl- (D3) greater than methyl- (D1) greater than ethyl- (AZQ) greater than i-butyl- (D6) greater than i-propyl- (D4) substituted derivatives. The hydroxyethylamino analog (BZQ) was not a substrate for DTD. The order of toxicity to HT-29 human colon carcinoma cells (at 1-log cell kill) was MeDZQ greater than DZQ greater than BZQ greater than D1 greater than D5 greater than AZQ greater than D7 greater than D3 greater than D6 greater than D4. Dicumarol, a known inhibitor of DTD, was capable of inhibiting the cytotoxicity of DZQ, MeDZQ, AZQ, D3, D4, D5, D6, and D7, with little inhibition of D1 cytotoxicity. Alkaline elution assays suggested that DZQ induced DNA strand breaks, whereas MeDZQ induced DNA interstrand crosslinks in HT-29 cells. The formation of both classes of lesions was inhibited by dicumarol. DZQ and MeDZQ were 5-6-fold less cytotoxic to the DTD-deficient BE cell line, whereas BZQ was more cytotoxic to this cell line than the HT-29 cell line. BZQ was capable of inducing dicumarol-insensitive DNA interstrand crosslinks in both cell lines. In summary, these data show a trend between the rate of reduction by DTD of an analog and its ability to induce cytotoxicity in HT-29 cells, and they support a role for DTD in the bioreductive activation of AZQ and its analogs.

Animals↗
PubMed1992

Cell-specific metabolism in mouse bone marrow stroma: studies of activation and detoxification of benzene metabolites.

Two of the major cell types in bone marrow stroma, macrophages and fibroblasts, have been shown to be important regulators of both myelopoiesis and lymphopoiesis. The enzymology relating to cell-specific metabolism of phenolic metabolites of benzene in isolated mouse bone marrow stromal cells was examined. Fibroblastoid stromal cells had elevated glutathione-S-transferase (4.5-fold) and DT-diaphorase (4-fold) activity relative to macrophages, whereas macrophages demonstrated increased UDP-glucuronosyltransferase (UDP-GT, 7.5-fold) and peroxidase activity relative to stromal fibroblasts. UDP-GT and glutathione-S-transferase activities in macrophages and fibroblasts, respectively, were significantly greater than those in unpurified white marrow. Aryl sulfotransferase activity could not be detected in either bone marrow-derived macrophages or fibroblasts, and there were no significant differences in GSH content between the two cell types. Because UDP-GT activity is high in macrophages, these data suggest that DT-diaphorase levels would be rate limiting in the detoxification of benzene-derived quinones in bone marrow macrophages. The peroxidase responsible for bioactivation of benzene-derived phenolic metabolites in bone marrow macrophages is unknown but has been suggested to be prostaglandin H synthase (PGS). Hydrogen peroxide, but not arachidonic acid, supported metabolism of hydroquinone to reactive species in bone marrow-derived macrophage lysates. These data do not support a major role for PGS in peroxidase-mediated bioactivation of hydroquinone in bone marrow-derived macrophages, although PGS mRNA could be detected in these cells. Similarly, hydrogen peroxide, but not arachidonic acid, supported metabolism of hydroquinone in a human bone marrow homogenate. Peroxidase-mediated interactions between phenolic metabolites of benzene occurred in bone marrow-derived macrophages. Bioactivation of hydroquinone to species that would bind to acid-insoluble cellular macromolecules was increased by phenol and was markedly stimulated by catechol. Bioactivation of catechol was also stimulated by phenol but was inhibited by hydroquinone. These data define the enzymology and the cell-specific metabolism of benzene metabolites in bone marrow stroma and demonstrate that interactions between phenolic metabolites may contribute to the toxicity of benzene in this critical bone marrow compartment.

Aged↗
PubMed1991

NAD(P)H:quinone oxidoreductase (DT-diaphorase) activity and mRNA content in normal and neoplastic mouse lung epithelia.

DT-diaphorase (DTD) is a flavoprotein which catalyzes obligate two-electron reduction of a diverse group of substrates. We have reported previously that non-tumorigenic mouse lung alveolar type-II pneumocytes have high DTD activity, while cell lines derived from lung tumors do not. In contrast, other investigators, using human lung tissue, reported increased DTD activity in tumors compared with normal tissue. We therefore investigated DTD associated with mouse lung neoplasia in vivo as well as in vitro. Pulmonary tumors had far less DTD activity compared with normal mouse lung. Correspondingly, a tumorigenic mouse lung cell line which arose as a spontaneous transformant of a normal cell line had very low DTD activity compared with non-tumorigenic lung cells. DTD-specific mRNA levels were also much higher in normal cell lines than in neoplastic ones. DTD was localized histochemically in type-II pneumocytes in situ, but was not observed by this technique in normal bronchiolar epithelia or in tumor cells. These data show that, unlike what has been observed in human lung cancer, a marked decrease in DTD content and activity accompanied mouse lung tumorigenesis in vivo and neoplastic transformation in vitro.

Animals↗
PubMed1991

Intraoperative radiation therapy for recurrent head and neck cancer.

Forty-seven patients with recurrent head and neck cancer in a previously irradiated field were treated with surgical resection and intraoperative radiation therapy (IORT). Recurrent disease occurred at a median of 18 months from primary treatment, and was at the primary tumor site in 31 and metastatic to regional lymph nodes in 16. Recurrences were squamous cell carcinomas in 42 and adenoid cystic in five. Surgical resection left microscopic residual disease in 41 and gross residual in six. All patients received IORT with a median of 20 Gy. Two-year actuarial survival is 54.9%, and 15 patients are alive and disease free with a median survival of 29 months. Two-year actuarial local control is 61.5%. A trend toward increased survival (P less than 0.09) and local recurrence control (P = 0.05) was noticed when treating microscopic residual disease as opposed to gross residual disease. Perioperative mortality was seen in 8.5% and there was no increase in morbidity secondary to IORT. The authors believe that surgical resection and IORT is an effective treatment modality for head and neck cancers recurrent in previously irradiated fields and is adaptable to tertiary care hospitals.

Combined Modality Therapy↗
PubMed1991

INFORM: integrated support for decisions and activities in intensive care.

Many medical decision support systems that have been developed in the past have failed to enter routine clinical practice. Often this is because the developers have failed to analyse in sufficient detail the precise user requirements, because they have produced a system which takes too narrow a view of the patient, or because the decision support facilities have not been sufficiently well integrated into the routine clinical data handling activities. In this paper we discuss how the AIM-INFORM project is setting out to deal with these issues, in the context of the provision of decision support in the intensive care unit.

Artificial Intelligence↗
PubMed1991

Users' perceptions of a computerised information system in intensive care (ABICUS) on introduction and after 2 months use.

The aim of the present study was to assess the perceived utility of a computerised information system in an intensive care unit (ICU). Questionnaires were devised in which ICU staff indicated the ease or difficulty of obtaining and recording information (a) under the previous manual system, (b) soon after the introduction of the computerised system and (c) two months after computerisation. Results indicated the system was well received immediately and this favourable attitude persisted unchanged after two months experience. The questionnaire method also served to pinpoint some particular interface problems which are to be remedied in future versions of the system.

Attitude of Health Personnel↗
PubMed1991

Replacement of the aortic valve with a pulmonary autograft: the "switch" operation.

The transfer of the patient's own pulmonary valve to the aortic position developed from our earlier work with aortic homografts. The valve shows no progressive tissue failure and offers the prospect of a permanent valve replacement for young people. Like homografts, the valves can be inserted in the subcoronary position or as a root replacement. In infants and growing children root replacement should be used to benefit from the valve's growth potential.

Age Factors↗
PubMed1991

Technique of aortic valve replacement with a homograft: orthotopic replacement.

Homograft replacement of the aortic valve has become increasingly popular. The technique of insertion is essentially simple but a number of variations have developed over the years. The valve can be inserted in orthotopic (subcoronary) position or as a root replacement. The technique described here has developed over the past 28 years and links up with the related operation of pulmonary valve translocation (pulmonary autograft).

Aortic Valve↗
PubMed1991

Effects of host age on infection of ICR mice with Echinostoma caproni or E. trivolvis.

There was no significant difference in the number of E. caproni recovered 21 days post-infection from 1-, 2-, 4-, 5-, 6-, 7-, 12-, or 21-month-old ICR mice infected with 25 metacercarial cysts. A range of 10.8-17.3 worms was recovered from mice in the age groups. In a similar experiment with E. trivolvis, there was no significant difference in worms recovered in young vs old mice. A range of 0-1.7 worms was recovered from mice in each age group. Contrary to a previous study on E. caproni in NMRI mice, our results indicate that host age does not affect establishment of E. caproni or E. trivolvis in the ICR mouse.

Age Factors↗
PubMed1991

Potential role of free radicals in benzene-induced myelotoxicity and leukemia.

Occupational exposure to benzene, a major industrial chemical, has been associated with various blood dyscrasias and increased incidence of acute myelogenous leukemia in humans. It is established that benzene requires metabolism to induce its effects. Benzene exposure in humans and animals has also been shown to result in structural and numerical chromosomal aberrations in lymphocytes and bone marrow cells, indicating that benzene is genotoxic. In this review we have attempted to compile the available evidence on the role of increased free radical activity in benzene-induced myelotoxic and leukemogenic effects. Benzene administration to rodents has been associated with increased lipid peroxidation in liver, plasma, and bone marrow, as shown by an increase in the formation of thiobarbituric-acid reactive products that absorb at 535 nm. Benzene administration to rodents also results in increased prostaglandin levels indicating increased arachidonic acid peroxidation. Other evidence includes the fact that bone marrow cells and their microsomal fractions isolated from rodents following benzene-treatment have a higher capacity to form oxygen free radicals. The bone marrow contains several peroxidases, the most prevalent of which is myeloperoxidase. The peroxidatic metabolism of the benzene metabolites, phenol and hydroquinone, results in arachidonic acid peroxidation and oxygen activation to superoxide radicals, respectively. These metabolites, upon co-administration also produce a myelotoxicity similar to that observed with benzene. Recently, we have found that exposure of human promyelocytic leukemia (HL-60) cells (a cell line rich in myeloperoxidase), to the benzene metabolites, hydroquinone and 1,2,4-benzenetriol results in increased steady-state levels of 8-hydroxydeoxyguanosine a marker of oxidative DNA damage. Peroxidatic metabolism of benzene's phenolic metabolites may therefore be responsible for the increased free radical activity and toxicity produced by benzene in bone marrow. We thus hypothesize that free radicals contribute, at least in part, to the toxic and leukemogenic effects of benzene.

Animals↗
PubMed1991

A note on the inhibition of DT-diaphorase by dicoumarol.

The participation of DT-diaphorase or NAD(P)H:(quinone acceptor) oxidoreductase (E.C. 1.6.99.2) in metabolism or in events leading to toxicity is often implied on the basis of the inhibitory effects of dicoumarol. DT-diaphorase functions via a ping pong bi-bi kinetic mechanism involving oxidized and reduced flavin forms of the free enzyme. Dicoumarol, a potent (Ki = 10 nM) inhibitor, binds to the oxidized form of the enzyme, competitively versus reduced pyridine nucleotide. Inhibition is effectively complete at 1 microM dicoumarol in typical studies using DCPIP, one of the best known substrates for the enzyme, as electron acceptor. The antitumor quinone Diaziquone (AZQ) is a poor substrate for DT-diaphorase relative to DCPIP, but effective inhibition of its reduction requires ten-fold higher concentrations of dicoumarol than for inhibition of DCPIP reduction under otherwise similar conditions. The variable inhibition of DT-diaphorase by dicoumarol dependent on the efficiency of the electron acceptor can be explained on the basis of the complete rate equation describing its ping pong type kinetic mechanism. Thus, the concentration of dicoumarol used to inhibit DT-diaphorase must be chosen carefully and consideration should be given to the efficiency of the electron acceptor. The absence of an inhibitory effect using low doses of dicoumarol cannot rule out a reaction mediated by DT-diaphorase. Although higher doses of dicoumarol may be required to inhibit DT-diaphorase mediated metabolism of less efficient electron acceptors, the use of such doses in cells may also affect biochemical processes other than DT-diaphorase and should be approached with caution.

Animals↗
PubMed1991

Aortic root replacement--20 years experience of the use of homografts.

The aortic root was replaced with a free root homograft 100 times in 91 patients from 1970 to January 1987. The ages of the patients were in the range 5-73 years (mean 29.7). There were 63 males and 34 females. Thirty had endocarditis with root abscesses. Forty-one had congenitally small aortic roots and 20 patients had such severe root calcification that root replacement was required. One patient had an aortic sinus aneurysm repaired using this technique. Operative mortality (overall 24%) analysed by operative indication was highest for prosthetic endocarditis (33%). 20% of those with root calcification and 15% of those operated on for hypoplastic roots died. Endocarditis was cured in 19 of 20 survivors. One patient needed repeat root replacement to achieve this. Thirteen patients out of 35 survivors in the hypoplastic group were restudied. Mean subvalvular gradient was 12 +/- 9 mmHg (range 0-27 mmHg). Late mortality was lowest in the endocarditis group (5%), and 11% in the hypoplastic group. There were 4 (24%) late deaths in the root calcification group but 2 were non cardiac. Eight homograft roots failed, two in the endocarditis group and one in the hypoplastic group due to endocarditis. The remainder failed because of 'wear and tear'. Five were replaced using homografts and one by a composite graft. Two were treated by prosthetic subcoronary aortic valve replacement with pericardial patch enlargement of the root. A further patient with Marfan's syndrome had an infected composite graft. This was replaced by a homograft root. There are 5 long term survivors of 7 repeat aortic root replacements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Pulmonary autograft aortic valve replacement: long-term results.

Since 1967, 339 cases of replacement of the aortic valve with the patient's pulmonary valve have been carried out in the National Heart Hospital and the Harley Street Clinic, London. The operation was introduced following the finding of progressive degeneration in previously placed homograft valves. The longest follow-up is 24 years and the cumulative total follow-up is 3,986 patient-years. Overall hospital mortality is 7.4% (25 cases) but with only one death after 1976. Late mortality is 38 patients and actuarial survival is 80% at 20 years. No anticoagulants have been used and there have been no emboli. Bacterial endocarditis occurred in 11 patients. Reoperation was carried out in 33 patients. Freedom from replacement is 85% at 20 years. There is no evidence of calcification or progressive tissue degeneration and the explanted valves show viable tissue. There is also accumulating evidence that the valve can grow in children. The actuarial freedom from all events is 70% at 20 years. With the current low operative risk and absence of progressive degenerative change plus growth prospects, it offers a potentially permanent valve replacement for infants, children, and young adults.

Adolescent↗