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Biomedical subjects

M R Johnston

Publications and source records attributed to M R Johnston.

At least 19 recordsLinked to original sources
PubMed2001

Validation of an orthotopic model of human lung cancer with regional and systemic metastases.

BACKGROUND: We developed an orthotopic model of human lung cancer that exhibits highly predictable regional and systemic metastases. This study examines the response of the model when treated with conventional and experimental chemotherapy. METHODS: NCI-H460 tumor fragments were implanted into the right caudal lung lobe of a nude rat. Treatment commenced 2 weeks later. We assessed response by comparing primary tumor and mediastinal lymph node weights, total body weight, and length of survival with untreated, tumor-bearing control animals. We also calculated the incidence of metastasis to kidney, bone, brain, and contralateral lung in treated versus untreated animals. RESULTS: Mitomycin and cisplatin showed broad activity against primary and metastatic disease. The matrix metalloproteinase inhibitor batimastat, low-dose cisplatin, and mitomycin significantly prolonged survival. High-dose cisplatin caused renal toxicity that shortened survival. Brain metastases did not respond to mitomycin, consistent with its poor blood-brain barrier penetration. CONCLUSIONS: Responses were similar to NCI-H460 in vitro data and consistent with clinical experience for these drugs. Drug-related toxicities similar to those seen in clinical practice were detected.

Analysis of Variance↗
PubMed2001

Preoperative assessment for pulmonary resection.

Because of recent advances in anesthesia and surgery, almost any patient with a resectable lung malignancy is now an operative candidate, given a full understanding of the risks and provided he or she is investigated appropriately. This progress necessitates a change in the paradigm that one uses for preoperative assessment. Understanding and stratifying the perioperative risks allows the anesthesiologist to develop a systematic focused approach to these patients at the time of the initial contact and immediately before induction, which then can be used to guide anesthetic management (Fig. 7).

Anesthesia↗
PubMed2000

The biology of some intraerythrocytic parasites of fishes, amphibia and reptiles.

Fishes, amphibia and reptiles, the ectothermic vertebrates, are hosts for a variety of intraerythrocytic parasites including protists, prokaryotes, viruses and structures of uncertain status. These parasites may experience host temperature fluctuations, host reproductive strategies, population genetics, host habitat and migratory behaviour quite unlike those of endothermic hosts. Few blood infections of fishes, amphibia and reptiles have proven pathogenicity, in contrast to the many intraerythrocytic parasites of mammals and some birds which harm their hosts. Although not given the attention afforded to intraerythrocytic parasites of endotherms, those of ectotherms have been studied for more than a century. This review reports on the diversity, general biology and phylogeny of intraerythrocytic parasites of ectotherms. The existence of taxonomic confusion is emphasized and the main taxonomic features of most of the 23 better characterized genera, particularly the kinetoplastid and apicomplexan protists, are summarized. Transmission of protistan infections of aquatic ectotherms is also discussed. Leeches can transfer sporozoties or merozoites to the vertebrate host during feeding. Dormant sporozoites of Lankesterella may permit transmission of species of this genus between vertebrates by predation. The fish haemogregarine, Haemogregarina bigemina, probably has gnathiid isopods, rather than leeches, as its definitive hosts. Hepatozoon spp. in aquatic hosts, and Progarnia of caiman, may also use invertebrate hosts other than leeches. Protistan infections of terrestrial or semi-terrestrial hosts are transmitted by a variety of arthropods, or, in some cases, leeches, contaminated paratenic hosts, or sporocysts free in water. Transfer of protists between vertebrates by predation and congenitally may also occur. The biology of the host cells of these infections, the red blood cells of ectotherm vertebrates, is summarized and compared with that of mammalian erythrocytes. Erythropoiesis, the nature of the surface molecules (especially the possible existence of a major histocompatibility complex), the haemoglobins, and the shape and size of erythrocytes are discussed. The exoerythrocytic sites in which protists, prokaryotes, viruses and structures of uncertain status exist before erythrocyte entry are described. Tissue merogony, tissue cysts and invasion of the white cell series occur in a variety of protistan infections. Intraerythrocytic stages of protistan infections are also discussed, including modes of entry to erythrocytes, survival mechanisms, and multiplication. The impact of infection on host populations is difficult to assess, in part because there is no agreement in the literature on the criteria used to evaluate parasite-induced cost to the host. Almost all studies have been on haemogregarine and Plasmodium infections in, mainly, lizards, but also fishes and snakes. Some infections may be responsible for mortality in their hosts, but hosts themselves may be short-lived, or have a limited ability to recover from infection.

Amphibians↗
PubMed2000

A study of smoking, p53 tumor suppressor gene alterations and non-small cell lung cancer.

PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53IHCS) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53IHCS > 1. p53 IHC was associated with increasing tumor size (T) (p = 0.035), nodal status (N) (p = 0.091), stage (p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) (p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking variables. In multivariate proportional hazards analysis, p53IHCS and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53IHCS and PY were 1.20 (95% CI 1.02-1.40) and 1.03 (95% CI 1.01-1.04), and for death due to recurrent disease (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respectively. Comparing the 75th percentile to the baseline 0, the adjusted HR for p53IHCS (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for the outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53IHCS are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC.

Adenocarcinoma↗
PubMed1999

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.

Bone Neoplasms↗
PubMed1999

Characterization of a highly metastatic, orthotopic lung cancer model in the nude rat.

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32-35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32-35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (>60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32-35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.

Animals↗
PubMed1998

Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study.

Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment.

Adult↗
PubMed1998

The role of endoscopy in the staging and management of lung metastases.

Endoscopic evaluation of the patient with lung metastases takes on many forms depending upon the extent of disease and the intent of treatment, be that curative or palliative. Thorascopy, and occasionally mediastinoscopy, may be helpful in assessing operability in patients with extensive disease on a preoperative computed tomography scan. However, when in doubt, exploration is always indicated in the young, good risk patient. Palliative efforts usually concern airway obstruction and malignant effects. A variety of technologies, including laser, brachytherapy, and endoluminal stents, helps manage symptomatic bronchial or tracheal lesions.

Airway Obstruction↗
PubMed1997

The limits of surgical resection alone for non-small cell lung cancer.

Surgical resection remains the best treatment for Stages I and II non-small cell lung cancer. In Stage IIIA disease the use of induction therapy has become widespread, although evidence supporting this approach is still preliminary. However, in subsets of patients with T3 tumours without mediastinal nodal involvement and those with certain single station, non-bulky N2 disease, surgery alone is still the preferred therapy. Studies show survival rates with surgery alone the same or higher than those achieved by most induction therapy regimens.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Electrophysiological analysis of the response of males of the potato cyst nematode, Globodera rostochiensis, to fractions of their homospecific sex pheromone.

Electrophysiological techniques and behavioural assays were used to determine the response of males of Globodera rostochiensis to 4 fractions of the homospecific sex pheromone from virgin females, separated using reverse-phase high-pressure liquid chromatography. Sex pheromone activity was confined to 2 of the fractions. The sex pheromone of G. rostochiensis appears to be composed of several weakly basic, polar compounds.

Animals↗
PubMed1997

Assessing children's ultraviolet radiation exposure: the use of parental recall via telephone interviews.

OBJECTIVES: This study evaluated the validity of a parental report measure of children's solar protection behaviors. METHODS: Fifty-eight children had skin color assessed twice with a colorimeter. Between measurement sessions, parents were interviewed by telephone to assess children's indoor-outdoor status and solar protection across 40 hourly intervals. RESULTS: Parental report of child's indoor-outdoor status was significantly correlated with the colorimeter values, whereas the use of sunscreen and protective clothing was not. CONCLUSIONS: This measure was feasible for assessing ultraviolet exposure in young children. The component that assessed the number of intervals spent outdoors evidenced predictive validity.

Child↗
PubMed1997

Curable lung cancer. How to find it and treat it.

Appropriate selection of lung cancer patients for potentially curative surgery demands a careful staging workup. The most adverse prognostic factors should be investigated first because their presence precludes consideration of potentially curative surgical therapy. Best surgical results are obtained in patients with early stages of disease. A quality lung cancer operation requires open thoracotomy with en bloc resection of the tumor and involved adjacent structures and thorough lymph node sampling or resection. Uninvolved lung tissue may be preserved with a variety of surgical techniques that do not compromise the curative intent of the procedure.

Biopsy↗
PubMed1997

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs.

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological changes were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study.

Animals↗
PubMed1996

Assessing children's ultraviolet radiation exposure: the potential usefulness of a colorimeter.

OBJECTIVES: This study evaluated the colorimeter as an objective measure of children's ultraviolet (UV) radiation exposure. METHODS: Fifty-eight children, ages 6 to 9 years, attended two summer measurement sessions, with 46 attending a subsequent winter session. RESULTS: Comparisons between summer sessions for the L* scale showed that only the upper arm significantly changed in the tanner direction, while b* scale values indicated significant tanning for all body sites. All exposed body sites changed significantly in the less tan direction between summer and winter measurements. CONCLUSIONS: Using colorimeters to objectively measure children's UV exposure has potential applications for skin cancer prevention programs.

Child↗
PubMed1995

Time-related effects of enzymatic disaggregation on model human lung carcinomas.

Enzyme cocktails used to prepare tumor cell suspensions may influence yield, viability, and cytology, thus time-related cocktail effects on model human lung carcinomas were examined. A549, NCI-H125, and NCI-H460 carcinomas were completely disaggregated at 25 degrees C over 2 h with either (mg/ml) collagenase/DNAase (C/D, 1/0.1), collagenase/hyaluronidase/DNAse (C/H/D, 1/0, 1/0.1), or polymyxa protease/DNAse (PP/D, 3/0.1). Trypan blue viabilities, total yields, viable yields, and flow cytometric percent tumor cells (TC) were measured every 20-30 min (n = 4-7 per tumor type). The final percentages of TC, mononuclear cells (MN), polymorphonuclear cells (PMN), lymphocytes, and necrotic cells were determined by cytology (n = 4-5 per tumor type). The time-dependent measurements showed that 1) disaggregation was progressive and complete with all cocktails; 2) viability was stable or increasing with all cocktails; 3) percent TC was stable for all cocktails, but lower for PP/D than C/D in final suspensions; and 4) PP/D gave lower final total yields, higher final viabilities, but the same final viable yields as the C cocktails, suggesting selective elimination of dead cells by PP/D. Final cytology measurements showed that PP/D gave a lower percent MN and a higher percent PMN than C cocktails. Cocktail effects may importantly influence cell suspension properties.

Animals↗
PubMed1995

Adenocarcinoma of the neo-esophagus after Collis gastroplasty.

The development of an invasive adenocarcinoma arising from gastric mucosa within the neo-esophagus of a Collis gastroplasty is uncommon. We report 1 patient in whom an adenocarcinoma developed 18 years postoperatively, and who was treated by total gastrectomy. We suggest accurate preoperative evaluation and staging to distinguish tumors arising in the distal esophagus from those arising in the gastric mucosa of the neo-esophagus, and recommend an approach to management of these tumors.

Adenocarcinoma↗