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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

At least 325 records · Page 18Linked to original sources
PubMed1987

Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas.

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.

Adolescent↗
PubMed1987

Pharmacokinetics of metronidazole in patients with alcoholic liver disease.

The pharmacokinetics of metronidazole was evaluated in eight patients with alcoholic liver disease. Metronidazole (7.5 mg/kg) was administered to each patient intravenously. Serial blood samples were obtained after the dose. Serum metronidazole concentrations were determined by high-performance liquid chromatography. The following pharmacokinetic parameters (mean +/- standard deviations) were obtained: half-life, 18.31 +/- 6.06 h; elimination rate constant, 0.042 +/- 0.013 h-1; volume of distribution, 0.77 +/- 0.16 liters/kg; and total body clearance, 0.51 +/- 0.11 ml/min per kg. Compared with subjects with normal liver function, patients with liver disease showed a reduction in drug elimination rate and total body clearance. The half-life of metronizadole in serum and volume of distribution were increased. Large variations of these parameters were also observed among the patients. On the basis of these observations, a reduced dose of metronidazole should be given to patients with alcoholic liver disease to avoid accumulation of metronidazole and its metabolites. Monitoring of drug concentration in serum may also be necessary to optimize therapy.

Adult↗
PubMed1987

Chronic sinoatrial disorder (sick sinus syndrome): a possible result of cardiac ischaemia.

Postmortem angiography was used to examine the blood vessels supplying the sinoatrial node in 25 subjects with chronic sinoatrial disorder (group 1). The results were compared with similar studies in 54 subjects who died of heart block and in whom sinus node function was normal (group 2). Although no significant lesion obstructing the blood flow to the sinus node was seen in the majority of those in group 1, there were abnormalities in seven cases, with reduced filling of the sinus node artery in five. In group 2 the sinus node artery filled normally in all cases despite major disease of the parent vessel in three. The combination of contralateral coronary artery disease with extensive atrial anastomoses was actively sought because this arrangement might predispose to a steal phenomenon. Such conditions were fully met in three cases in group 1 and two cases in group 2, and were found to a lesser extent in a further two cases in group 1 and three in group 2. Although coronary artery disease was unlikely to be the principal cause of sinus node dysfunction in most of the cases studied it was relatively common and may have been a factor in about one third. Improved survival after myocardial infarction may increase the number of patients with chronic sinoatrial disorder of ischaemic origin.

Aged↗
PubMed1987

The clinical features of Ehlers-Danlos syndrome type VII due to a deletion of 24 amino acids from the pro alpha 1(I) chain of type I procollagen.

The clinical features and progress of a child with the type VII form of Ehlers-Danlos syndrome due to a deletion in the pro alpha 1(I) of type I procollagen were studied. The child was born with bilateral dislocations of hips and knees and all other joints were markedly hypermobile. Persistent severe joint instability was the major clinical abnormality. She had a depressed nasal bridge with prominent paranasal folds and deeply set eyes with mild hypertelorism and micrognathia. The skin was soft, moderately hyperelastic, and sagged over the face and knees. Skin fragility and easy bruising appeared when she started walking. Electron microscopy of the dermis showed irregular collagen fibrils.

Amino Acid Sequence↗
PubMed1987

Interleukin-2 production and response to interleukin-2 by peripheral blood mononuclear cells from patients after bone marrow transplantation: II. Patients receiving soybean lectin-separated and T cell-depleted bone marrow.

The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA-identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL-2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.

Adult↗
PubMed1987

Improved survival of infants less than 1 year of age with acute lymphoblastic leukemia treated with intensive multiagent chemotherapy.

Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Early disease recurrence, rather than excessive toxicity and complications resulting in limitation of therapy is the major factor responsible for this disappointing outcome. The CCG-192P trial was a groupwide pilot study of the Childrens Cancer Study Group for the treatment of ALL in patients at high risk for relapse, which was defined by wbc count greater than 50 X 10(3)/microliters at diagnosis. Because of the recognized poor prognosis, all infants less than 1 year of age were entered in this study regardless of wbc count at diagnosis. Therapy included intensive induction and consolidation followed by a cyclic, sequential maintenance program. The CNS prophylaxis consisted of intrathecal chemotherapy and cranial irradiation, which was deferred until patients were greater than 1 year of age. During the period January 1982 to January 1984, 27 infants ranging in age from 2 days to 11 months who had ALL were entered in this study; 71% had wbc counts greater than 50 X 10(3)/microliters, and 23% presented with CNS leukemia. Complete remission was achieved in 93% of the patients. The median duration of remission is 17 months. With a median follow-up of 43 months, the life-table estimate of event-free survival (EFS) is 36% at 4 years. A recently reported historical control group of infants with ALL who were treated with previous Childrens Cancer Study Group protocols demonstrated a median remission duration of 8 months and an estimated EFS of only 21% at 4 years. Toxicity and therapy-related complications were not observed more frequently in infants than in older patients treated with this protocol. However, EFS of infants was significantly worse than that of patients greater than 1 year of age (P = less than 0.001). All four CNS relapses occurred in patients who had received cranial irradiation. A wbc count less than 50 X 10(3)/microliters at diagnosis demonstrated significance (P = 0.03) as a favorable prognostic indicator in this small patient sample. Although these data are preliminary, they suggest that intensive therapy is reasonably well tolerated by infants and results in prolongation of remission duration and improved EFS.

Age Factors↗
PubMed1987

National trends in the morbidity and mortality of asthma in the US. Prevalence, hospitalization and death from asthma over two decades: 1965-1984.

National population-based data systems of the National Center for Health Statistics (NCHS) were used to study the epidemiology of asthma in the United States over the last 20 years. Asthma is more prevalent among males, those living below the poverty level, persons living in the South and West, and blacks; however, this difference did not attain statistical significance. Death rates from asthma among the older age groups probably increased between 1968 and 1982, with a substantial increase since 1979. For children, the evidence is less clear, but the death rate has increased for children over five years of age during the period from 1979 to 1982. Between 1964 and 1980, asthma has become more prevalent in children under 17 years of age, but this does not reflect an increase in the severity of asthma over this same time period. Hospitalization rates for asthma between 1965 and 1983 increased by 50 percent in adults and by over 200 percent in children. Rates for black patients are 50 percent higher in adults and 150 percent greater in children. It is concluded that there has been a marked increase in hospitalization rates for asthma, a moderate increase in death rates from asthma and a smaller increase in overall prevalence of the disease in the United States.

Activities of Daily Living↗
PubMed1986

The immunological network at the site of tumor rejection.

The tumor mass irrespective of its type or location in the body has long been shrouded in mystery and even today we still have only a tentative handle on its secrets. Attempts to manipulate either the tumor cells per se or host-derived leukocytes have, on the whole, not been successful or at best questionable. The ability of the host to respond immunologically to TSTA is well documented, yet again attempts to manipulate this response have been disappointing. One of the problems has been a lack of knowledge concerning the tumor mass and its constituents, such as the intratumor leukocytes, and the significance of their presence to the biological properties of the neoplasm [8,9,80]. The purpose in studying the immunological network is, in part, to try to assign a function to these cells on the premise that lymphoid elements and macrophages have a potential role to play in recognition of TSTA. The advantage of adoptive immunotherapy model systems is that tumor rejection can be achieved under controlled conditions and this allows an analysis of the immunological network and its individual circuits. At the same time, valuable information on the mechanisms of action during adoptive immunotherapy and how best to improve therapeutic protocols is acquired.

Animals↗
PubMed1986

Protochemotherapy in non-small cell lung carcinoma. An attempt to increase surgical resectability and survival. A preliminary report.

Twenty patients with Stage IIIM0 (T3N2) non-small cell lung cancer were treated with vindesine, etoposide, and Platinol (cisplatin) (ELETOP) chemotherapy in an attempt to decrease tumor size and increase resectability and survival. ELETOP chemotherapy induced a 70% response rate (all partial responses) within 6 weeks, and three patients were able to undergo curative resection. Toxicities with ELETOP were moderately severe, with leukocyte and platelet nadirs on day 15. This pilot study demonstrates the feasibility of protochemotherapy in non-small cell lung cancer.

Adult↗
PubMed1986

Expression of class II-MHC antigens by tumor-associated and peritoneal macrophages: systemic induction during tumor growth and tumor rejection.

It was shown previously that combination therapy of tumor-bearing mice resulted in amplification of antitumor responses at the site of tumor rejection and involved some of the classical components of the immunological network. As a continuation of this work, we now show that amplification of immune responses involves an increase in class II-MHC antigen (Ia) expression both at the tumor site and peripherally in the peritoneal cavity. Of further interest, however, was the observation that there was also an increase in Ia expression by tumor-associated macrophages (TAM) and peritoneal macrophages (PMs) in mice bearing progressing tumors. In these experiments, Ia expression by TAM and PMs was assessed in C57BL/6J mice bearing the progressing syngeneic MCA/76-9 sarcoma as well as in mice that had received combination therapy consisting of an intraperitoneal injection of cyclophosphamide (CY) and an intravenous injection of tumor-sensitized T lymphocytes (immune cells). When progressing tumors were analyzed, it was seen that by the fourth day after tumor cell implantation, 45-60% TAM expressed Ia, a level that was sustained throughout the course of tumor growth. The treatment of tumor-bearers with CY had no effect on Ia expression by TAM. However, the number of Ia-expressing TAM increased significantly after combination therapy and, as the tumors regressed, reached a peak of up to 100% in the second week after therapy. TAM were shown by Northern blot hybridization to contain mRNA encoding for the Ia beta chain. When Ia expression by PMs was assessed, it was seen that during tumor progression there was an increased expression of Ia over background (from less than 10 to about 40%), beginning 9-12 days after tumor cell implantation and continuing for the duration of the experiments. This was not influenced by CY injection. Combination therapy significantly increased the number of PMs expressing Ia (up to 80%). Ia expression by PMs could be induced rapidly in vivo by injecting normal B6 mice intraperitoneally (ip) with T cells isolated from tumors induced to regress by combination therapy. PMs isolated up to 15 days after injection were shown to express Ia. Moreover, the ip injection of a mixture of specific MCA/76-9 tumor cells and these tumor-associated lymphocytes resulted in a more rapid rate and a higher level of Ia expression by PMs compared with the level induced by either treatment alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Muir-Torre syndrome.

The patient with sebaceous skin tumors and visceral malignancies, Muir-Torre syndrome, is presented. The documentation of tumors in 8 of 13 members in her kindred supports the concept that this syndrome represents a cancer-disposing phenotype.

Adenocarcinoma↗
PubMed1986

Sexual rehabilitation and male radical cystectomy.

Sexual function was assessed before radical cystectomy in 112 men: 20 per cent were sexually inactive and 35 per cent had erectile dysfunction. Sexual function before cystectomy was an index of general health status and correlated significantly with survival free of disease. Followup data on sexual function were provided by 73 men at an average of 13 months postoperatively. After cystectomy, which was performed via standard operative techniques, 91 per cent of the men experienced some degree of erectile dysfunction but 50 per cent remained sexually active, at least using noncoital stimulation. Thirteen men chose to have a penile prosthesis implanted. Sexual counseling was rated as satisfactory by 80 per cent of the men.

Adult↗
PubMed1986

Niche expansion in bacteria: can infectious gene exchange affect the rate of evolution?

Recombination occurs by infectious gene transfer in bacteria, at rates much lower than recombination by sexual reproduction in other organisms. Thus, recombination may accelerate evolution in bacteria only under restricted conditions, such as occur when mutations at several loci are required for the evolution of an expanded ecological niche. Mathematical ("chemostat") models of several such cases--evolution of independence from three limiting essential or "interactive-essential" resources; evolution of the ability to use three new substitutable resources; and evolution of resistance to three growth inhibitors--were analyzed by computer simulation. All combinations of three mutation rates (U) and four values for the "infectious gene transfer rate parameter" (chi) were considered. Recombination accelerated evolution most when U was low and chi was high, but was unlikely to have large effects when chi was low enough to be realistic for natural populations of Escherichia coli. Recombination had the largest effects when resources were substitutable, and in that case could have substantially reduced the chance of random loss of the favored "triple mutant" while it was still rare. The simulations also revealed some interesting features of selection for an expanded niche. Evolution of independence from essential resources occurred more rapidly when the resources were weakly complementary than when they did not interact. Selection for the ability to use all substitutable resources was weak after all intermediate types that used only one or two of the resources had arisen.

Anti-Bacterial Agents↗
PubMed1986

Anxiety and endocrine changes in surgical patients.

There is a need for research to identify the relationship between psychological and endocrine responses to surgical operations, and to discover whether these responses differ with variations in practice between different settings. This preliminary study investigated 17 patients undergoing middle ear operations in two hospitals. Measurements included state anxiety, Recovery Inventory, cortisol excretion and noradrenaline excretion. All were made pre-operatively and on three post-operative days. Recovery Inventory correlated (between subjects) with state anxiety, but this relationship was confined to the post-operative days. No correlation between a psychological measure and an endocrine one reached significance. There was a non-significant tendency for pre-operative anxiety to be lower in one ward than another; cortisol levels were significantly higher in the same ward overall. These results do not support a view that anxiety is related to processes mediating physical recovery. Explanations for the difference in cortisol levels are considered. It is suggested that the influence of pre-operative psychological preparation on endocrine responses deserves systematic investigation.

Adult↗