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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

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

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

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

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

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

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

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

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

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

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

Biochemical analyses on single amphidial glands, excretory-secretory gland cells, pharyngeal glands and their secretions from the avian nematode Syngamus trachea.

The gape nematode, Syngamus trachea, has been used as a model to study nematode secretions. Individual and intact pairs of amphidial glands, pharyngeal glands and pairs of excretory-secretory gland cells have been dissected and their secretory products analysed. The protein profiles of each gland and the total nematode secretions were analysed on 12.5% homogeneous SDS-PAGE minigels. The protein analyses revealed that the structural protein profile of each gland is different. The amphidial gland secretes two major proteins of 36.0 and 41.5 kDa, the excretory-secretory gland cell secretes a protein of 28.2 kDa and a protein of 14.3 kDa, and the pharyngeal gland secretes proteins of 41.5 and 14.6 kDa. Analysis of the total nematode secretions revealed all of the above major secretory proteins and an additional protein of 49.3 kDa. Syngamus trachea secretes acetylcholinesterases and its secretions contain multiple proteases.

Animals

Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma to the lung or diffuse bronchioloalveolar carcinoma.

Eight patients with metastatic sarcoma to the lung (n = 4) or diffuse bronchioloalveolar carcinoma of the lung (n = 4) underwent isolated lung perfusion with chemotherapy in a pilot study. Ages ranged from 18 to 60 years and half were female. The left lung was perfused in three patients (single lung perfusion) and both lungs in five patients (total lung perfusion). Perfusions ranged from 45 to 60 minutes at ambient or normothermic temperatures. One patient received perfusion at moderate hyperthermia (40 degrees C). Escalating doses of doxorubicin (1 to 10 micrograms/ml perfusate) was used in six patients, whereas two received cisplatin (14 and 20 micrograms/ml perfusate). There were two major complications and no objective responses. The isolated perfusion systems gave excellent separation between systemic and pulmonary circulations with zero to 15% of the measured peak drug concentration of the pulmonary perfusate detected in the systemic circulation. Drug concentrations in normal lung and tumor generally increased with higher drug dosages and drug was detectable in mediastinal lymph nodes of three out of four patients in whom sampling was done. Isolated lung perfusion with chemotherapy can be done safely in patients with lung malignancies and evidence suggests that higher drug dosages should be well tolerated.

Adenocarcinoma, Bronchiolo-Alveolar

Investigation of the chemosensory function of amphids of Syngamus trachea using electrophysiological techniques.

Syngamus trachea, the gape nematode, has been used as a model to study the chemosensory function of amphids. Extracellular electrophysiological recordings were performed directly on amphids. The amphids were stimulated by blood serum from a host bird and by D-tryptophan. The spike frequency produced by the amphid increased significantly after the application of the serum and the application of D-tryptophan. Two types of amphidial neurones responded to the presence of the stimuli. These extracellular recordings have verified the chemosensory function of the amphids.

Action Potentials

Why should thoracic surgeons understand basic biology?

Thoracic surgery is undergoing major changes. In addition to the well publicized political and economic upheavals, our patients and the diseases targeted are rapidly evolving. Much of the change is driven by an explosion of new biology that many in the field have little or no familiarity with. As molecular biology, immunology, and information about cytokines pervade our literature and practices, it is imperative that thoracic surgeons develop a basic understanding of these and other unique concepts. The best link between our clinical practice and the new biology is thoracic surgical scientists who are exposed to current information.

Animals

Lung perfusion and other methods of targeting therapy to lung tumors.

As therapies for cancer and other diseases continue to evolve on a molecular and genetic basis, delivering these sophisticated agents will continue to be problematic. Although the agents may be highly effective in the laboratory, their true worth can only be measured by clinical responses. In certain instances, the skills of a thoracic surgeon may be called upon to provide the means of delivering therapy rather than to perform therapy, as is our custom. The techniques discussed in this review are just a few of the many possibilities for targeting agents in an effort to enhance their clinical efficacy.

Adenocarcinoma, Bronchiolo-Alveolar

Dose-related doxorubicin effect in an orthotopic secondary lung cancer screen.

Lung cancer is the leading cause of cancer-related death of both sexes in the United States and promises to be a major problem in the world community for decades. We are developing an orthotopic (organ specific) secondary screening system to measure the uptake and efficacy of new lung cancer agents. The elements of the system are: (1) orthotopic growth of a model human lung cancer (NCI-H460 large cell carcinoma) in the right caudal lobe of the nude rat; (2) 1-hr ex vivo pulmonary perfusion treatment of the tumor-bearing lungs; and (3) soft agar clonogenic assay of the enzymatically disaggregated tumor cells. This study characterizes dose-response aspects of the system. Perfusion of tumor-bearing lungs with 0, 1, 10, and 100 micrograms/ml doxorubicin resulted in a dose-related reduction in surviving fraction from 1.01 +/- 0.41 to 0.019 +/- 0.006 (P < 0.05) without significant treatment-related increases in lung weight or perfusion pressure. Tumor and lung drug levels were also dose-related, with lung levels exceeding tumor levels at all doses. The tumor drug level at the 100 micrograms/ml dose was 62 +/- 16 ng/mg. There was a strong negative correlation between the measured tumor drug level and surviving fraction in the clonogenic assay (R2 = 0.47, P = 0.0005). This new screening system is capable of demonstrating dose-related uptake and tumoricidal activity of doxorubicin on an orthotopic, model human large cell lung carcinoma. It may be useful for the secondary screening of agents active against human lung cancer.

Animals

Use of pleural Tenckhoff catheter to palliate malignant pleural effusion.

Malignant pleural effusion and its treatment both cause substantial morbidity in patients with advanced neoplastic disease. We hypothesized that this morbidity might be ameliorated by placement of an indwelling Tenckhoff catheter into the involved pleural space. Catheters were placed in 9 patients under local anesthesia. Three patients underwent bilateral catheter placement, for a total of 12 catheters placed. Four of the 9 patients had undergone previous unsuccessful pleurodesis (using tetracycline or bleomycin). Whenever it became symptomatic, the malignant pleural effusion was simply drained into a calibrated container and the volume recorded. Patients were followed on a weekly basis until their death (mean, 16 weeks). The mean drainage was 477 mL per 24 hours (range, 200 to 1,100 mL). No pleural space infections occurred, although local cellulitis developed in 3 patients around the catheter exit site; all patients responded to oral antibiotics. There were no significant changes in either the serum albumin or total protein levels. No catheters malfunctioned and no patients required further treatment or hospitalization for symptoms of malignant pleural effusion. We conclude that this technique may reduce the morbidity stemming from malignant pleural effusion and its treatment by allowing patients to conveniently and painlessly drain the effusion at home when it becomes symptomatic. This technique may provide superior palliation in patients with malignant pleural effusion.

Adult