Biomedical subjects

D Payne

Publications and source records attributed to D Payne.

At least 145 records · Page 8Linked to original sources

PubMed1993

Use of an enzyme-linked immunosorbent assay (ELISA) to measure the expression of the K88 fimbrial antigen by enterotoxigenic Escherichia coli (ETEC).

A solid-phase enzyme-linked immunosorbent assay (ELISA) has been developed to detect and quantify the K88 fimbrial adhesin antigen. The assay was used to detect cell-bound antigen present in bacterial suspensions and cell-free K88 antigen present in extracts. Comparable amounts of K88 antigen were detected with whole bacteria and in the equivalent extracts. The assay was used to compare the expression of the K88 antigen by one laboratory strain (K12:K88ab) and three wild-type strains (O8:K87:K88ab:H19, O8:K87:K88ac:H19 and K88ad) of enterotoxigenic Escherichia coli (ETEC) during cultivation with eight medium types and two medium forms. Determination of the expression of K88 during unshaken batch culture revealed a correlation between growth phase and expression, with maximal concentrations being detected during late log to early stationary phase. Colony blotting experiments demonstrated that expression of the K88 antigen was under quantitative and not qualitative control.

Antigens, Bacterial↗

PubMed1993

Detection of human papillomavirus type 16 in plasma cells.

Chronic benign plasma cell tumor of the cervix, also called chronic plasma cell cervicitis, is a rare disease of unknown etiology, characterized by a heavy infiltration of plasma cells forming granulation tissue. To identify infectious agents associated with this disease, we extracted and analyzed DNA from the 17-year-old paraffin section of the original case report and from granulation tissue surgically removed from a patient at our institution with a chronic benign plasma cell tumor. The DNA from both patients was shown by a polymerase chain reaction (PCR) technique to contain a human papillomavirus 16 (HPV 16) sequence. Genomic Southern analysis of the fresh-frozen tissue confirmed the initial PCR finding. In situ hybridization further demonstrated that the HPV 16 was present in the plasma cells and not a contaminant from the surrounding epithelial tissue. The etiological role of HPV 16, an oncogenic virus associated with cervical carcinoma, in this disease is not yet clear. Our results, however, suggest that the types of cells that are infected by HPV may include cells of lymphoid origin, and that HPV may be associated with chronic benign plasma cell tumors of the cervix.

Aged↗

PubMed1993

Squamous cell carcinoma of the lip: analysis of the Princess Margaret Hospital experience.

We reviewed 117 patients with squamous cell carcinoma of the lip who were treated at the Princess Margaret Hospital between 1976 and 1985. Ninety-eight cancers arose from the lower lip, 18 from the upper lip and 1 from the commissure. Two patients had lymph node metastases at presentation. Sixty-one patients were treated with radiation therapy following a biopsy, 28 underwent surgery followed by post-operative radiation, and 28 had surgery alone. With a median follow-up time of 5.4 years, the 5-year actuarial overall and cause-specific survival rates were 81% and 99%, respectively. Local failure developed in 4 patients after radiation treatment, 3 of whom were salvaged by surgery. Six patients developed regional metastases after initial treatment, 4 of whom were salvaged with surgery and/or radiotherapy. Two patients died from lip cancer. After a univariate analysis, the only factor which predicted for nodal failure was T stage of the primary lesion, with a 4% risk of nodal failure for T1 lesions vs. 20% for T2/3 lesions (p = 0.03). No other patient, tumour or treatment variables influenced loco-regional control or survival in a statistically significant manner. Cosmetic and functional outcome were evaluated in 8 patients whose radiation treatments were administered 13 years ago. No patients had compromised lip function, and the majority had minimal cosmetic sequelae from their radiation therapy. Based on the excellent results of this review, we would continue to recommend radiation therapy as an effective treatment modality for patients with lip cancer because of the ease by which the entire tumour can be encompassed whilst maintaining excellent cosmetic and functional outcome.

Adult↗

PubMed1993

Transesophageal echocardiography for hemodynamic management of thoracoabdominal aneurysm repair.

Maintenance of cardiovascular stability during thoracoabdominal aneurysm repair remains a formidable challenge. Transesophageal echocardiography (TEE) has been shown to be an excellent method for detecting myocardial ischemia and assessing left ventricular volume. We examined the utility of TEE in a group of 17 patients from an overall series of 33 patients who underwent thoracoabdominal aneurysm resection between 1988 and 1992. The mortality rate was 9%, whereas the incidences of myocardial infarction and paraplegia were 13% and 6%, respectively. Intraoperative management was significantly altered by TEE data in nine patients. Two patients were noted to have mitral valve insufficiency, and one had transient ischemia-induced regional wall abnormalities. In six patients, Swan-Ganz-derived filling data failed to identify severe hemodynamic alterations that were noted on TEE. Five patients were hypovolemic and hyperdynamic, whereas one was in florid congestive heart failure. Further investigation is warranted to prospectively validate this technique.

Adult↗

PubMed1993

The K88 fimbrial adhesin of enterotoxigenic Escherichia coli binds to beta 1-linked galactosyl residues in glycosphingolipids.

The K88 fimbrial adhesin enables certain strains of enterotoxigenic Escherichia coli to adhere to the porcine small intestine. In this study, the ability of the K88 adhesin to bind to glycosphingolipids was monitored by modified enzyme-linked immunosorbent assay and thin-layer chromatography overlay binding analysis. The binding of the K88 adhesin to glycosphingolipid-coated microtiter plates was saturable, with 50% maximal binding occurring with gangliotriaosylceramide, gangliotetraosylceramide, and lactosylceramide at 67 +/- 21, 117 +/- 21, and 73 +/- 22 pM, respectively. Thin-layer chromatography overlay binding analysis demonstrated that serotype O8:K87:K88ab:H19 E. coli bound to hydroxylated galactosylceramide, gangliotriaocylceramide, gangliotetraosylceramide, and lactosylceramide but not to globotriaosylceramide, nonhydroxylated galactosylceramide, glucosides, glucosylceramide, or a mixture of ceramides. The K88 adhesin did not bind by either assay to globoside, the Forssman glycolipid, GM1, GM2, GM3, GD1a, GD2, GD3, GQ1b, or GT1b. The binding pattern observed with the K88 adhesin suggests that beta 1-linked galactosyl residues are the minimum determinant required for binding, provided they are presented correctly. It is suggested that beta 1-linked galactose residues may form the molecular basis of both glycoprotein and glycolipid receptors for the K88 fimbrial adhesin in the porcine small intestine.

Adhesins, Escherichia coli↗

PubMed1993

Nitric oxide donors reduce the rise in reperfusion-induced intestinal mucosal permeability.

Recent data have demonstrated that inhibition of nitric oxide synthesis exacerbated the mucosal injury associated with reperfusion of the postischemic intestine. In this study, using a feline 1-h intestinal ischemia followed by reperfusion model, we tested the possibility that exogenous sources of nitric oxide may prevent the reperfusion-induced mucosal barrier disruption and examined the mechanisms involved. Mucosal barrier integrity was assessed by determining 51Cr-EDTA clearance from blood to lumen. Intestinal blood flow and resistance were also determined. Reperfusion after 1 h of ischemia significantly increased 51Cr-EDTA clearance (0.05 +/- 0.01 to 0.35 +/- 0.07 ml.min-1.100 g-1) and decreased intestinal blood flow by 50%. Exogenous sources of nitric oxide including SIN-1, CAS-754, and nitroprusside as well as exogenous L-arginine all reduced reperfusion-induced mucosal barrier dysfunction without improving intestinal blood flow. Inhibition of endogenous nitric oxide with NG-nitro-L-arginine methyl ester between 1 and 2 h of reperfusion further augmented the rise in mucosal permeability associated with ischemia-reperfusion. Addition of the permeable analogue of guanosine 3',5'-cyclic monophosphate, 8-bromoguanosine 3',5'-cyclic monophosphate, improved reperfusion-induced intestinal blood flow significantly but did not provide protection against mucosal barrier disruption associated with the first hour of ischemia-reperfusion. Exogenous sources of nitric oxide can reduce reperfusion-induced mucosal barrier dysfunction independent of alterations in intestinal blood flow.

Animals↗

PubMed1993

Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial. METHODS: All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks). RESULTS: Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006). CONCLUSION: The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.

Aged↗

PubMed1993

Chronic plasma cell cervicitis simulating a cervical malignancy: a case report.

BACKGROUND: Only one case of plasma cell cervicitis, a rare variant of chronic cervicitis, has been reported. We report a second case and present data supporting the detection of human papillomavirus (HPV) outside of epithelial tissues. CASE: A 67-year-old woman was found to have a large cervical tumor. Extensive diagnostic evaluation failed to reveal a suspected cervical cancer; subsequently, a hysterectomy was performed. Light microscopic studies confirmed plasma cell cervicitis. Standard virologic tests were used to confirm the presence of HPV 16 in cervical sections. Retrospective study of the first reported case also demonstrated HPV. CONCLUSION: Fulminant cases of chronic cervicitis, presenting with clinical features similar to cervical cancer, are unusual. Even more interesting is the detection of HPV outside of the epithelium; this is the first case that clearly demonstrates HPV in plasma cells.

Aged↗

PubMed1992

Second primary malignancies following diagnosis of small-cell lung cancer.

PURPOSE AND METHODS: The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. RESULTS: Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. CONCLUSION: We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Aged↗

PubMed1992

Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis.

PURPOSE: Our main purpose was to determine whether the addition of thoracic radiation therapy to systemic chemotherapy improves 2-year survival, improves local (intrathoracic) tumor control, and affects treatment-related mortality in patients with limited-stage small-cell carcinoma of the lung. DESIGN: Eleven randomized trials addressing this issue were identified using a computerized literature search (Medline and Cancerline) and by polling senior investigators in the field. A meta-analysis was then performed and the results of the trials were analyzed in two ways, the odds ratio (OR) (Peto) method and the risk difference method (Dersimonian and Laird). RESULTS: The overall OR for benefit of thoracic radiation on 2-year survival (ie, the odds of surviving 2 years among patients allocated to radiation compared with the odds of surviving 2 years among patients allocated to control) is 1.53 (95% confidence interval [CI], 1.30 to 1.76; chi 2 = 12.76; P less than .001). The risk difference method showed that radiation therapy improved 2-year survival by 5.4% (95% CI, 1.1% to 9.7%). Local control results were available for only nine studies, the OR for treatment benefit is 3.02 (95% CI, 2.80 to 3.24; chi 2 = 101.48; P less than .0001), and intrathoracic tumor control was improved by 25.3% (95% CI, 16.5% to 34.1%). The OR for excess treatment-related deaths in the thoracic radiation-treated patients was 2.54 (95% CI, 1.90 to 3.18; chi 2 = 8.24; P less than .01). The risk difference for treatment-related deaths was 1.2% (95% CI, -0.6% to 3.0%). CONCLUSIONS: This meta-analysis shows a small but significant improvement in survival and a major improvement in tumor control in the thorax in patients receiving thoracic radiation therapy. However, this is achieved at the cost of a small increase in treatment-related mortality.

Carcinoma, Small Cell↗

PubMed1991

The dynamics of drug resistance in Plasmodium falciparum.

Drug resistance of Plasmodium falciparum is not a recent phenomenon, but it became a major problem when the parasite became resistant to chloroquine, the cheapest and initially the most effective antimalarial compound that could be used for treatment and suppression. In some areas this problem is compounded by resistance to the first line of alternative drugs, and rapid loss of sensitivity to the next line. The dynamics of drug resistance are regulated mainly by drug related selection pressure and intensity of malaria transmission. Mass drug administration in its various forms, and insufficient treatment are obviously the most important motors of selection.

Animals↗

PubMed1991

A management approach to incompletely excised basal cell carcinomas of skin.

There were 187 incompletely resected basal cell carcinomas (BCC) of skin referred to the Princess Margaret Hospital between 1970 and 1985. Median age at presentation was 62 years. The commonest location of these lesions was in the head and neck region (93%). One hundred twenty lesions were immediately treated: 119 were irradiated and 1 was excised. The remaining 67 lesions were managed expectantly. Follow-up time for the entire population ranged from 1 month to 17 years, with a median time of 2.7 years. The 5-year probability of remaining relapse-free in the group immediately treated was 91% versus 61% if managed expectantly (p = 0.0001). If only lateral margins were positive, the crude probability of local failure was 3/18 (17%), versus 9/27 (33%) if the deep margins were involved (p = 0.2). Once relapse occurred in the group of lesions treated expectantly, 17/20 (85%) of these relapses were salvaged by either radiation or surgery. The 10-year actuarial probability of local control for the lesions immediately treated and observed were similar: 92% and 90%, respectively (p = 0.5). An economic analysis revealed that immediate radiation treatment saved the health system only $223.00 per patient. Since there is no difference in the ultimate local control between these two approaches, and these elderly patients may be spared the morbidity of unnecessary treatments, it is suggested that a policy of observation may be adopted for basal cell carcinomas of skin which have been incompletely excised.

Actuarial Analysis↗

PubMed1991

Experience with zona drilling and zona cutting to improve fertilization rates of human oocytes in vitro.

Zona drilling (ZD) and zona cutting (ZC) were used in an IVF programme to assist fertilization in semen defect patients. Twenty-seven patients consented to ZD where acidified Tyrode's was used to create a hole in the zona pellucida. In 19 patients, ZD increased the fertilization rate to 29% compared with 8% (P less than 0.001) in their routine IVF cycles, and in eight patients precluded from routine IVF, a fertilization rate of 14% was achieved. Twenty-two patients consented to ZC where a slit in the zona is made mechanically. In 12 patients ZC increased the fertilization rate to 31% compared with 14% (P less than 0.01) from previous routine IVF cycles, and in 10 patients precluded from routine IVF, a fertilization rate of 34% was achieved. In 13 cycles, 68 uncut control oocytes were inseminated. In five cycles both control and ZC oocytes were fertilized (n.s.d.). In eight cycles no control oocytes were fertilized compared with 27% of ZC oocytes. The polyspermy rate was 4.6%. Twenty-four per cent of ZD and 12% of ZC (P less than 0.01) oocytes and embryos were degenerate after 42 h. Both ZD and ZC can increase the fertilization rate of sub-optimal semen, however, in our hands neither technique produced a pregnancy.

Cell Survival↗

PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗

PubMed1991

Small-cell carcinoma of the lung: derivation of a prognostic staging system.

Retrospective data on 22 pretreatment attributes were evaluated in 614 patients with small-cell carcinoma of the lung (SCCL). The series included 284 patients with limited disease (LD) and 328 patients with extensive disease (ED) managed between 1974 and 1986. Prognostic factors were evaluated by univariate analysis and by the Cox multivariate regression model. Recursive partition and amalgamation algorithm (RECPAM), two clustering methods well suited for obtaining strata and adapted for censoring survival data, were developed and used in the formulation of a new prognostic staging system. In univariate analysis, prognosis was significantly influenced by extent of disease (DE), the number of metastatic sites, and the detection of mediastinal spread in LD. Poor performance status (PS), male sex, and advanced age were negatively correlated with survival, as were increased serum levels of alkaline phosphates (AP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), total WBC count (WBCC), and low platelet count and low serum sodium. The Cox model identified plasma LDH and mediastinal spread as the only significant factors in LD; the influence of PS, number of metastatic sites, bone metastasis, brain metastasis, and platelet count were identified as significant in ED. The RECPAM model identified four distinct risk groups defined in a classification tree by the following eight attributes: DE, PS, serum AP, serum LDH, mediastinal spread, sex, WBCC, and liver metastasis. The four groups were distinguished by median survival times of 59, 49, 35, and 24 weeks, respectively (P = .0001). Interactions among prognostic factors are emphasized in the RECPAM classification model as evidenced by reassignment of patients across conventional staging barriers into alternate prognostic groups. The advantages of using RECPAM over the more conventional Cox regression techniques for a new staging system are discussed.

Adult↗

PubMed1991

Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia.

Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa. The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly. The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs. The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively. In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant. The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006). P. falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively. All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences. In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.

Adult↗

PubMed1990

Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome.

The in vivo and in vitro response of Plasmodium falciparum to a single oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15] was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for young children the therapy appears to be complicated by frequent vomiting.

Animals↗