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Biomedical subjects

D Ross

Publications and source records attributed to D Ross.

At least 253 records · Page 14Linked to original sources
PubMed1988

Differentiation of aseptic and bacterial meningitis in postoperative neurosurgical patients.

The differentiation of bacterial from aseptic meningitis in postoperative neurosurgical patients has traditionally been based on the clinical setting, a recent history of steroid administration, and cerebrospinal fluid (CSF) studies, including the total and differential leukocyte counts, Gram stain, glucose, and total protein. Recent reports questioning both the validity of a relative CSF lymphocytosis in excluding bacterial meningitis and the usefulness of standard CSF testing prompted the authors to reevaluate these standard criteria. The type of operation, the presence of a foreign body, use of steroids, postoperative day on which symptoms developed, altered mental status, neck stiffness, headache, and nausea were not helpful in the differential diagnosis. High fever, new neurological deficits, an active CSF leak, and elevated leukocyte counts in the CSF and peripheral blood favored a bacterial etiology. The CSF glucose level and the differential leukocyte count were less helpful. No criterion or combination of criteria was sensitive and specific enough to reliably differentiate aseptic from bacterial meningitis in the majority of patients. The possibility of improving diagnostic accuracy with newer tests, such as CSF lactate, ferritin, total amino acids, C-reactive protein, and amyloid-A, should be assessed.

Bacterial Infections↗
PubMed1988

Presumed intraocular nocardiosis in a cardiac-transplant patient.

A 44-year-old cardiac-transplant patient receiving immunosuppressive therapy developed a chorioretinal mass OS. The lesion was consistent with an ocular nocardial infection. The patient also developed a testicular abscess that was shown to contain N. asteroides after orchiectomy. Despite appropriate systemic treatment, the patient developed extensive subretinal scarring OS. This case report is the first to describe an opportunistic ocular infection with N. asteroides after cardiac transplantation.

Adult↗
PubMed1987

Cytotoxicity of the redox cycling compound diquat in isolated hepatocytes: involvement of hydrogen peroxide and transition metals.

Diquat is a hepatotoxin whose toxicity in vivo and in vitro is mediated by redox cycling and greatly enhanced by pretreatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. The mechanism by which redox cycling mediates diquat cytotoxicity is unclear, however. Here, we have attempted to examine the roles of three potential products of redox cycling, namely superoxide anion radical (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (.OH), in the toxicity of diquat to BCNU-treated isolated hepatocytes. Addition of high concentrations of catalase, but not superoxide dismutase, to the incubations provided some protection against the toxic effect of diquat, but much better protection was observed when catalase was added in combination with the iron chelator desferrioxamine. Addition of desferrioxamine alone also provided considerable protection, whereas the addition of copper ions enhanced diquat cytotoxicity. Taken together, these results indicate that both H2O2 and the transition metals iron and copper could play major roles in the cytotoxicity of diquat. The role of O2-. remains less clear, however, but studies with diethylenetriaminepentaacetic acid indicate that O2-. is unlikely to significantly contribute to the reduction of Fe3+ to Fe2+. The hydroxyl radical or a related species seems the most likely ultimate toxic product of the H2O2/Fe2+ interaction, but hydroxyl radical scavengers afforded only minimal protection.

Animals↗
PubMed1987

N-methyl antitumour agents. A distinct class of anticancer drugs?

This article reviews the structure-activity characteristics, mode of action, pharmacokinetics and clinical utility of a group of chemically dissimilar antitumour agents which have as a common structural feature the N-methyl moiety. The importance of this feature is shown by the fact that molecules without a substituent on the nitrogen or compounds with N-alkyl groups other than methyl are usually inactive in experimental systems. This observation is supported by structure-activity studies with N-alkyl derivatives of s-triazines, triazenes, formamides, hydrazines and nitrosoureas. Representatives of these structural types which have found clinical application are, respectively, hexamethylmelamine, dacarbazine, N-methylformamide, procarbazine and streptozotocin. Mode of action studies have shown that dacarbazine, procarbazine and streptozotocin can give rise to species capable of methylating nucleic acid. This may be the lesion which produces antitumour activity. The mechanism of action of N-methylmelamines and N-methylformamide remains unclear. There is good evidence that, with the exception of N-methylnitrosoureas, host metabolism is prerequisite for activity with these agents. Although not pronounced, the clinical activity of N-methyl antitumour agents is useful, particularly as activity is not associated with severe haematological toxicity. Furthermore, responses may be observed in patients resistant to bifunctional alkylating agents. It is concluded that the drugs reviewed herein show a degree of coincidence in terms of their biological properties which may warrant a common classification. The term N-methyl antitumour agent is proposed.

Alkylating Agents↗
PubMed1987

Metabolic activation of 1-naphthol and phenol by a simple superoxide-generating system and human leukocytes.

Phenol and 1-naphthol, products of benzene and naphthalene biotransformation, are metabolized during O2- generation by xanthine oxidase/hypoxanthine and phorbol myristate acetate (PMA)-stimulated human neutrophils. The addition of 1-naphthol to xanthine oxidase/hypoxanthine incubations resulted in the formation of 1,4-naphthoquinone (1,4-NQ) whereas phenol addition yielded only small quantities of hydroquinone, catechol and a unidentified reducible product but not 1,4-benzoquinone. This formation of 1,4-NQ was dependent upon hypoxanthine, xanthine oxidase, and 1-naphthol and was inhibited by the addition of superoxide dismutase (SOD) demonstrating that the conversion was O2-mediated. During O2- generation by PMA-stimulated neutrophils, the addition of phenol interfered with luminol-dependent chemiluminescence and resulted in covalent binding of phenol to protein. Protein binding was 80% inhibited by the addition of azide or catalase to the incubations indicating that bioactivation was peroxidase-mediated. In contrast, the addition of 1-naphthol to PMA-stimulated neutrophils interfered with superoxide-dependent cytochrome c reduction as well as luminol-dependent chemiluminescence and also resulted in protein binding. Protein binding was only partially inhibited by azide or catalase. The addition of SOD in combination with catalase resulted in a significantly greater inhibition of binding when compared to that of catalase alone. The results of these experiments indicate that phenol and 1-naphthol are converted to reactive metabolites during superoxide generating conditions but by different mechanisms. The formation of reactive metabolites from phenol was almost exclusively peroxidase-mediated whereas the bioactivation of 1-naphthol could occur by two different mechanisms, a peroxidase-dependent and a direct superoxide-dependent mechanism.

Benzoquinones↗
PubMed1987

Metabolic activation of diethylstilbestrol by stimulated human leukocytes.

Previous studies have implicated both peroxidases and leukocytes in the metabolic activation of the human carcinogen diethylstilbestrol (DES). Here we demonstrate that DES is converted during the oxidative burst of human leukocytes to reactive protein binding species. Although luminol-dependent chemiluminescence indicated that peroxidase-dependent metabolism was occurring, the protein binding was not inhibitable by azide. This suggested that either peroxidase-mediated metabolism was not responsible for the formation of the reactive protein binding species or that this binding was occurring in a cellular compartment inaccessible to azide. The addition of catalase alone and in combination with superoxide dismutase (SOD) did, however, result in significant inhibition of binding. Hypochlorous acid was also shown to be capable of directly converting DES to protein binding species. These results indicate that a product of the oxidative burst, most likely a highly oxidizing species derived from H2O2, is capable of converting DES to a potentially carcinogenic binding species.

Catalase↗
PubMed1987

Intraoperative radiation therapy for advanced or recurrent head and neck cancer.

Between 1982 and 1984, we treated 28 patients with advanced head and neck cancer with surgery, combined with intraoperative radiation. All patients had squamous cell carcinoma. One patient had two separate sites treated and a second patient was treated on two occasions, allowing 30 sites for analysis. The overall survival for all patients treated was 67% at 1 year. Local failure occurred in 13% of those with close surgical margins and 25% of those with microscopic residual disease. With gross residual disease 100% had local failure. Patients with gross residual disease had significantly higher local failure than microscopic residual disease (p less than 0.02) or close surgical margins (p less than 0.01). Carotid blowout was the major treatment complication. We believe intraoperative radiation is an effective treatment for advanced or recurrent head and neck cancer when all gross disease has been resected.

Carcinoma, Squamous Cell↗
PubMed1987

Method for individualizing patient care for chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease is a progressively debilitating disease that affects not only the patient's physical capabilities, but the patient's entire psychosocial network, including family and friends. A patient education program has been developed to assist each patient individually in dealing more effectively with all aspects of care.

Adaptation, Psychological↗
PubMed1987

Application of homografts in clinical surgery.

Aortic freehand homografts have been used since 1962 and are still our preferred method of treatment. They are centrally flowing and are consequently nonobstructive and give rise to neither emboli nor turbulence. They do, however, undergo a slow process of degeneration, giving plenty of time for an elective low risk second operation. An additional advantage is that they can be used in children. Various methods of valve preparation and storage have been used, but there is no clear evidence that one particular method is superior. The position of the homograft in the heart does have a bearing on its function, with the valve persisting longer in the low-pressure right heart chambers. Long-term results indicate that the unmounted homograft in the aortic area gives better results than currently used bioprostheses and in the right ventricular outflow tract there is no comparable valve. Studies of the viability of the various valve components and also their immunological significance should help to improve the long term durability of the homograft valve.

Adult↗