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Biomedical subjects

G J Johnson

Publications and source records attributed to G J Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1980

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗
PubMed1980

Decreased survival in vivo of diamide-incubated dog erythrocytes. A model of oxidant-induced hemolysis.

Erythrocytes from patients with chronic hemolytic variants of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have structural membrane protein abnormalities accompanied by decreased cell membrane deformability which we postulate represent the consequences of oxidant-induced membrane injury. To evaluate the pathophysiologic significance of oxidant-induced membrane injury, we studied the in vitro and in vivo effects of the thiol-oxidizing agent, diamide, on dog erythrocytes. In vitro incubation of dog erythrocytes with 0.4 mM diamide in Tris-buffered saline for 90 min at 37 degrees C resulted in depletion of GSH, formation of membrane polypeptide aggregates (440,000 and > 50,000,000 daltons) and decreased cell micropipette deformability, abnormalities similar to those observed in the erythrocytes of patients with chronic hemolytic variants of G-6-PD deficiency. In addition, diamide-incubated cells had increased viscosity and increased membrane specific gravity, but no change in ATP. Reinjection of 51Cr-labeled, diamide-incubated cells was followed by markedly shortened in vivo survival and splenic sequestration. Further incubation of diamide-incubated cells in 4 mM dithiothreitol reversed the membrane polypeptide aggregates, normalized micropipette deformability, decreased cell viscosity, prolonged in vivi survival, and decreased splenic sequestration. These studied demonstrate that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury. They suggest that oxidant-induced erythrocyte membrane injury plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants.

Adenosine Triphosphate↗
PubMed1980

Long-term treatment of systemic mastocytosis with histamine H2 receptor antagonists.

A patient with systemic mastocytosis, accompanied by gastric hypersecretion and duodenal ulcer, was treated with metiamide followed by daily cimetidine for 44 months. Treatment with cimetidine resulted in healing of the ulcer, without recurrence and marked amelioration of the cutaneous symptoms of mastocytosis. Complete suppression of basal gastric hypersecretion was documented after 33 months of treatment and cimetidine and Vitamin B12 absorption remained normal. Cimetidine reduced the patient's cutaneous response to intradermal histamine without affecting leucocyte histamine release. No cimetidine toxicity was observed. These results indicate that effective long-term control of histamine-induced gastric hypersecretion can be achieved with cimetidine. They suggest that some of the cutaneous symptoms of mastocytosis are mediated via histamine H2 receptors in the skin.

Adult↗
PubMed1979

Red-cell-membrane polypeptide aggregates in glucose-6-phosphate dehydrogenase mutants with chronic hemolytic disease. A clue to the mechanism of hemolysis.

Red-cell membranes from patients with glucose-6-phosphate dehydrogenase deficiency were studied with polyacrylamide gel electrophoresis and gel filtration chromatography in sodium dodecyl sulfate. Membranes from each of five such patients who also had chronic hemolytic disease contained polypeptide aggregates within two molecular-weight ranges (4.4 X 10(5) and greater than 50 X 10(6) daltons). The 4.4 X 10(5) dalton aggregates were not detectable in red-cell membranes of patients with the enzyme deficiency without chronic hemolysis or in membranes from normal subjects, and the greater than 50 X 10(6) dalton aggregates were not found in appreciable amounts in these cells. The aggregates were dissociated by mercaptoethanol or dithiothreitol -- indicating that they were formed by intermolecular disulfide bonds. The polypeptide aggregates contained spectrin but not globin. Red-cell deformability was decreased in aggregate-containing cells. We postulate that the polypeptide aggregates are indicators of oxidant damage to the red-cell membrane, which results in decreased deformability and chronic hemolysis.

Adolescent↗
PubMed1979

Opportunities for research in rural practice.

The contributions of Denis Burkitt, William Budd, Sir James MacKenzie and Will Pickles, among others, are examples of the research that can be accomplished by busy doctors in a general practice or a rural setting with a minimum of equipment. It is still possible to undertake worthwhile research in rural areas of Canada. This contention is supported by many examples of published work from northern Newfoundland and Labrador. The studies have dealt with conditions that are particularly frequent in each region, including those due to nutritional deficiency, infection, extremes of climate and genetic factors. Epidemiologic studies have compared the occurrence of disease in different geographic regions and in different races. The content of general practice and methods of health care delivery have also been investigated. It is suggested that some of these observations could have been made only in the context of rural medical practice.

Climate↗
PubMed1979

Survey of ophthalmic conditions in a Labrador community. I. Refractive errors.

Of the 745 available members of the population of Nain in Labrador 650 (87%) were screened for refractive errors and ocular disease. Refraction by retinoscopy was done in 553 and axial length measured by an optical method in 514. The results showed that the incidence of low degrees of myopia was higher in Inuit (Eskimos) and those of Mixed Inuit-Caucasian blood in the age groups 10 to 40 than in those over 40. 75% of the myopes came from 20 families in which myopia was present in 2 or more generations. Although there was no significant correlation between the refraction of parents and offspring, there were significant correlations between them for axial length. The axial lenths of the myopic eyes of the Inuit and Mixed populations were significantly longer than emmetropic and hypermetropic eyes. The younger memebers of the population were taller than their parents, and except in female Caucasians axial length showed a significant positive correlation with height. More myopes than emmetropes and hypermetropes achieved grade 8 or more in school. It is suggested that the increased incidence of myopia in the younger age groups might be due to environmental factors interfering with the process of emmetropisation in eyes with a genetic predisposition to myopia by virtue of inheriting a slightlt longer eye. Better nutrition resulting in an increase in stature may also have had some influence.

Adolescent↗
PubMed1979

In vivo platelet retention in human bleeding-time wounds. I. Normal subjects and patients with platelet dysfunction.

PRB was measured in standardized skin puncture wounds. Platelets in wound blood samples collected in EDTA-heparin-containing micropipettes were counted electronically following gravity separation of plasma. The relationship between the wound platelet count (expressed as percent of the venous blood platelet count) and time was found to be linear during the first 3 min of bleeding. The slope of the linear regression line for percent of venous blood platelet count vs. time was 20.8 +/- 8.9 (mean +/- S.D.) in 31 normal subjects. Nine of 10 patients with significant, nonpharmacologic platelet dysfunction were found to have markedly decreased PRB. The determination of PRB was found to be reproducible, and control studies excluded platelet clumping and sedimentation of platelets as factors which significantly influenced the results. In contrast to previous observations, the results of this study indicate that platelets are removed from circulating blood at an increasing rate during the first 3 min of bleeding in normal subjects. Furthermore, a significant degree of EDTA-reversible clumping of platelets normally occurs during bleeding. The method described permits an accurate assessment of the quantitative and dynamic aspects of platelet participation in the arrest of bleeding. The determination of PRB holds promise in the evaluation of the biological significance of in vitro evidence of platelet dysfunction, and it may be useful in the evaluation of patients with hemorrhagic and thromboembolic disorders.

Blood Coagulation↗
PubMed1979

In vivo platelet retention in human bleeding-time wounds. II. Effect of aspirin ingestion.

PRB was studied in normal human subjects before and after aspirin ingestion. Aspirin ingestion resulted in a prolongation of individual bleeding times greater than 2.4 min (greater than 2 S.D. beyond the group mean before aspirin) in 62.5% of 48 paired studies. The relationship of platelets retained vs. time was linear during the first 3 min of bleeding before and after aspirin. The mean PRB decreased from 22.1 +/- 9.2 to 9.6 +/- 8.6 (p less than 0.001) after aspirin ingestion. Subjects whose bleeding time was prolonged greater than 2.4 min had a significantly higher mean PRB before aspirin and a significantly greater mean decrease in PRB after aspirin than those whose bleeding time was prolonged less than or equal to 2.4 min. Aspirin ingestion reduced the number of EDTA-irreversible clumped platelets present in wound blood approximately 50% during the second and third minute of bleeding, but large numbers of EDTA-reversible platelet clumps were observed in wound blood before and after aspirin. Although platelet retention was significantly decreased during the first 3 min of bleeding after aspirin, the percent of venous blood platelets present in wound blood just prior to the arrest of hemorrhage was equal before and after aspirin. These observations indicate that aspirin prolongs the bleeding time by decreasing platelet clumping and slowing the rate of platelet thrombus formation in severed blood vessels. The presence of platelet clumps in wound blood after aspirin ingestion indicates that alternative mechanisms of platelet aggregation, independent of the arachidonate pathway of prostaglandin synthesis, proceed in vivo unaltered by aspirin.

Adult↗
PubMed1978

Histology of spheroidal degeneration of the cornea in Labrador.

Nine specimens of the corneas of patients from Labrador and Northern Newfoundland affected by spheroidal degeneration (climatic droplet keratopathy) have been examined microscopically. Histochemical stains confirmed studies of similar corneal degenerations from other geographical areas that the droplets contain a protein which does not have all the characteristic properties of elastic tissue. Staining compatible in some instances with fibrin and "fibrinoid" was found. By immunoperoxidase techniques the droplets were located in the zones of greatest concentration of various plasma constituents, especially albumin and immunoglobulins G and A. Reasons are given why the abnormal deposits are not thought to be derived directly from corneal collagen. It is suggested that some of the plasma proteins, which are known to be diffusing through the cornea from the limbal vessels under normal conditions are acted upon by the ultraviolet light reflected from the ice of Labrador and degraded so that they accumulate in the superficial stroma.

Aged↗
PubMed1978

Membrane polypeptide aggregates in glucose 6-phosphate dehydrogenase-deficient and in vitro aged red blood cells.

RBC membrane polypeptide aggregates have been quantitated by PAGE SDS and by gel filtration. Aggregates were absent in fresh RBC's from normal controls, but aggregates with MW 4.4 X 10(5) and greater than 50 X 10(6) increased progressively as GSH levels fell in RBC's incubated in PBS without added glucose or calcium. Aggregates of both MW ranges were also present in fresh RBC's from a patient with compensated congenital nonspherocytic hemolysis associated with a mutant RBC G-6-PD, Long Prairie. Since the aggregates were dissociable by treatment with mercaptoethanol or dithiothreitol, they are probably cross-linked by intermolecular disulfide bonds. Membranes containing these aggregates may represent an early and sensitive indicator of oxidative damage to red cells.

Erythrocyte Membrane↗
PubMed1978

Platelet dysfunction induced by parenteral carbenicillin and ticarcillin. Studies of the dose-response relationship and mechanism of action in dogs.

Sequential studies of platelet function were performed in dogs receiving continuous intravenous carbenicillin (CARB) or ticarcillin (TIC). Dose- and time-dependent platelet dysfunction was uniformly observed during the administration of CARB or TIC, 250 to 1000 mg/kg/24 hr. ADP-induced primary and secondary platelet aggregation was markedly inhibited within 24 to 48 hours in dogs receiving 750 or 1000 mg/kg/24 hr, but maximum impairment of aggregation did not occur until 3 to 5 days in dogs receiving 250 or 500 mg/kg/24 hr. Platelet glass bead column retention was abnormal in all dogs studied, and platelet factor 3 availability was impaired in 91%. Collagen-induced platelet aggregation was consistently impaired and the bleeding time was prolonged only during the infusion of greater than or equal to 750 mg/kg/24 hr. Plasma fibrinogen concentrations and thrombin times remained normal. CARB and TIC infusions resulted in inhibition of 14C-serotonin release and slightly decreased platelet ADP, while serotonin, ATP, and ultrastructure remained unchanged. The mutual correction of abnormal platelet aggregation by mixing CARB or TIC platelets with aspirin-treated platelets suggested that CARB and TIC inhibited the platelet release reaction by a mechanism other than inhibition of platelet cyclo-oxygenase. The platelet inhibitory properties of CARB and TIC demonstrated in this study suggest that they may be useful antithrombotic agents.

Adenosine Diphosphate↗
PubMed1978

Dose-dependent inhibition of experimental arterial thrombosis by carbenicillin and ticarcillin.

An experimental model of canine arterial thrombosis was used to study by prophylactic antithrombotic effectiveness of carbenicillin and ticarcillin, two semisynthetic penicillins which have been shown to inhibit platelet function in vivo. Isolated peripheral arterial segments were injected with pronase and biopsied at 24 hours. In untreated dogs, 89% of injected segments totally occluded with thrombus. Prophylactic treatment for 3 to 7 days with carbenicillin or ticarcillin in low doses (250 mg/kg/day) or high doses 750 mg/kg/day) significantly decreased the incidence of total occlusion to 53% and 6%, respectively. The dose-dependent inhibition of arterial thrombosis correlated with dose-dependent inhibition of platelet function. Prophylactic treatment with aspirin in low doses (650 mg/day) or high doses (2600 mg/day) did not significantly decrease the incidence of total occlusion in this model. Carbenicillin and ticarcillin are effective experimental antithrombotic agents.

Animals↗
PubMed1977

G-6-PD Long Prairie: a new glucose-6-phosphate dehydrogenase mutant exhibiting normal sensitivity to inhibition by NADPH and accompanied by nonspherocytic hemolytic anemia.

The enzymatic properties of a new glucose-6-phosphate dehydrogenase (G-6-PD) variant (G-6-PD Long Prairie) were studied in a white patient with chronic nonspherocytic hemolysis. The red cells were found to have 2.3%-7.7% normal enzymatic activity. The mutant enzyme exhibited marked heat instability, an increased pH optimum, a moderately decreased Km for G-6-P, and increased utilization of 2-deoxyglucose-6-phosphate and deamino NADP. The Km for NADP and Ki for NADPH were both normal. G-6-PD Long Prairie is an interesting new G-6-PD variant that demonstrates that chronic hemolysis can be associated with modestly decreased G-6-PD activity despite normal sensitivity to inhibition by NADPH. Although increased sensitivity to inhibition by NADPH has been postulated to decrease intracellular enzyme activity, resulting in enhanced susceptibility to hemolysis in certain G-6-PD variants with only moderately decreased enzymatic activity, an alternative mechanism of hemolysis, possibly enzyme thermolability, exists in G-6-PD Long Prairie.

Adult↗
PubMed1977

Chemotherapy of non-Hodgkin's lymphomas: Eastern Cooperative Oncology Group experience.

The addition of prednisone to the two-drug combination of cyclophosphamide and vincristine increases the number of complete remissions (CR). Patients who had CRs in at least two of the studies, EST 0168 and EST 3472, lived significantly longer than those who had partial remissions. In EST 0168, the survival time correlated strongly with the nodal pattern and cell type, confirming results of Rosenberg and co-workers. EST 1472 confirmed the activity of BCNU in lymphocytic lymphomas; when both agents are combined with prednisone, the induction potential of BCNU is equal to that of cyclophosphamide. In the histiocytic lymphomas, BCNU added to CVP increases the percentage of CRs but it does so at the expense of considerable toxicity. EST 0871 demonstrated that low-dose bleomycin and hexamethylmelamine are active agents in lymphoma and should be combined with other effective combinations in an attempt to improve the CR rate. Finally, our current studies demonstrate that the failure rate in the diffuse or unfavorable lymphomas is higher than that in the more favorable nodular forms.

Altretamine↗
PubMed1977

Epiblepharon in Labrador.

We describe the characteristic configuration of normal Inuit (Eskimo) eyelids. Exaggeration of some normal features of the lower lid can result in epiblepharon inferior. We have seen in Labrador seven patients with epiblepharon of a degree sufficient to require surgical intervention. All were Inuit or had distant Eskimo ancestry. We outline their clinical features and the technique of operation which has been evolved. The results were good. We stress the importance of making the distinction between entropion and epiblepharn because the operative treatments of the two conditions are different. The recommended surgical methods include, for some cases, excision of bulky orbicularis muscle as well as skin.

Adult↗