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J Johnston

Publications and source records attributed to J Johnston.

At least 163 records · Page 9Linked to original sources
PubMed1990

Sequential methotrexate, 5-fluorouracil, and leucovorin in metastatic measurable colorectal cancer. Does it work?

Four single-arm trials using methotrexate (M), 5-fluorouracil (5FU), and leucovorin (L) were sequentially performed in metastatic measurable colorectal cancer using different dosing and timing schedules for the three drugs. A total of 99 patients were entered into the trials, 92 (49 men and 43 women) of whom were evaluable for response. Although the first trial appeared to have a 36% response rate, the overall response rate seen in the four trials was not higher than historical reports of 5FU alone. We could find no correlation with dose intensity or patient characteristics to account for the apparent good results of the first trial. It is our conclusion that MFL is not an active combination in colorectal cancer. After progressing to the fourth trial, four patients were placed on 5FU alone (supported by a grant from Lederle, Canada). This resulted in one response in a patient who had not responded to the three-drug combination and stable disease in two patients previously progressing. Although there are many reports of this combination working, the possibility is raised that M may be inhibitory to the combination despite the in vitro data.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Examination of relative rates of cAMP synthesis and degradation in crude membranes of adipocytes treated with hormones.

The impact of changes in the activation state of the low Km cAMP phosphodiesterase (PDE) on cAMP output in adipocyte membranes was assessed by measuring the product of cAMP synthesis and degradation in the membrane preparation simultaneously. Crude membranes were prepared from adipocytes treated with the cAMP analog, 8-pCl phi S-cAMP and from adipocytes treated with 2 nM insulin. Using membranes from control and treated cells, adenylate cyclase was activated with various concentrations of forskolin and cAMP production (synthesis minus degradation) was measured with and without complete PDE inhibition using the specific inhibitor CI-914. Half maximal inhibition of the low Km cAMP PDEs in control membranes was produced by 1.16 +/- 0.07 microM CI-914 and greater than 98% of the activity was inhibited by 100 microM CI-914. The I50 and the concentration of CI-914 producing complete PDE inhibition in membranes from 8-pCl phi S-cAMP or insulin-treated cells were identical to those seen in membranes from control cells. Treatment of adipocytes with 8-pCl phi S-cAMP or with insulin did not modify basal rates of cAMP synthesis or alter the ability of adenylate cyclase to be activated by forskolin. The impact of PDE activity on cAMP accumulation was relatively small in membranes from control cells, but treatment of adipocytes with 8-pCl phi S-cAMP or with insulin activated the low Km cAMP PDE and caused a marked decrease in cAMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Structure of the cDNA encoding transcobalamin I, a neutrophil granule protein.

Transcobalamin I (TCI) is a member of the R binder family of vitamin B12 binding proteins. It is a major protein constituent of secondary granules in neutrophils. We have isolated and characterized full length cDNA clones encoding TCI in order to determine whether its expression is coordinately regulated with the appearance of secondary granules and whether it is consequently a useful marker of granulocyte development. Partial amino acid sequences of human R protein were obtained from tryptic digestion fragments. Using the polymerase chain reaction, a partial TCI cDNA probe was isolated by selective amplification of a region of cDNA located between two oligonucleotides deduced from the available partial amino acid sequences. The amplified probe was then used to obtain full length clones from a granulocyte cDNA library. Identity of the clones was confirmed by matching DNA sequence to known peptide amino acid sequence. TCI is transcribed to a single 1.5-kilobase mRNA species. The predicted protein sequence is 433 amino acids long. We have compared the sequence of TCI to that of rat intrinsic factor. The two proteins have areas of extensive homology which implicate regions potentially important for vitamin B12 binding. TCI mRNA was present in late neutrophil precursors but absent from uninduced and induced HL60 cells.

Amino Acid Sequence↗
PubMed1989

Bolus position at swallow onset in normal adults: preliminary observations.

A "delayed swallowing reflex/response" (i.e., when the swallow reflex is not triggered when the bolus passes the back of the tongue at the anterior facial arch) Logemann has been widely accepted as an abnormality. Careful review of the literature supports the premise that a "delayed swallowing reflex/response" may in fact be a variation of normal. This paper describes swallowing in normal adults. We report the videofluoroscopic measurements of bolus position at the onset of swallow. A radiopaque marker was affixed to the anterior facial arch and the distance between the head of the bolus and the anterior facial arch was measured at the onset of swallow. A statistically significant proportion of swallows (22 of 30) occurred after the head of the bolus passed the anterior facial arch. This finding suggests that there may be diverse sites for elicitation of the swallowing response/reflex rather than a single site (i.e., the anterior facial arch). The relevance of this finding to treatment using thermal stimulation is discussed, as is the versatility of the normal pharynx.

Adult↗
PubMed1989

Effects of ANP on venous pressures and microvascular protein permeability in dog forelimb.

Intravenous administration of alpha-atrial natriuretic peptide (ANP) produces a decrease in arterial blood pressure due to a decrease in cardiac output. The mechanism of the decrease in cardiac output is unknown but has been suggested to result from transcapillary fluid efflux caused by venoconstriction and/or increased permeability of the microvascular membrane to plasma proteins. We investigated these possibilities in the dog forelimb perfused at constant flow and prepared to measure 1) large and small vessel pressures in the two parallel skin and skeletal muscle vascular beds, and limb weight; or 2) skin lymph flow and skin lymph protein concentration. In both preparations, human ANP was injected and infused into the brachial artery. Bolus injections of ANP (0.1-0.4 micrograms) depressed perfusion pressure much less than acetylcholine or an isotonic solution of potassium chloride and did not raise small vein pressures. ANP infused at nine different rates ranging from 0.1 ng to 38.8 micrograms/min failed to influence skin and muscle small and large vein pressures, limb weight, skin lymph flow, and skin lymph protein concentration. It also failed to affect perfusion pressure and skin and muscle small artery pressures until the infusion was shut off, at which time they increased above control levels. These studies suggest that human alpha-ANP is neither a direct venous constrictor nor a potent arteriolar dilator and does not directly influence the permeability of the microvascular membrane to plasma proteins in the skin and skeletal muscle of the dog forelimb.

Animals↗
PubMed1989

Hemodynamic effects of bufalin in the anesthetized dog.

Studies in Lichstein's laboratory suggest that the endogenous digitalislike substance implicated in low renin hypertension might be a steroidal dienolide derivative. If this is true, the bufadienolides should block potassium vasodilation and enhance norepinephrine vasoconstriction, constrict blood vessels, raise blood pressure, and produce natriuresis and diuresis. We have therefore examined these parameters while infusing bufalin (aglycone), a bufadienolide, intrabrachially and intravenously in the anesthetized dog. Intrabrachial infusion of 5-25 micrograms/min with brachial arterial blood flow held constant at 100 ml/min produced a dose-dependent increase in perfusion pressure with rapid onset and offset, a progressive decrease in the vasodilator response to intrabrachial injection of 1 ml iso-osmotic potassium chloride solution (but not to acetylcholine), and an increase in the vasoconstrictor response to intrabrachial injection of 0.1 microgram norepinephrine. Intravenous infusion at 5-50 micrograms/min produced a dose-dependent increase in systemic arterial blood pressure, rate of change of ventricular pressure (dP/dt), and after the highest dose, cardiac irregularities. Natriuresis and diuresis were not observed. Thus, bufalin does in fact have some of the physiological properties required to be considered a candidate for the digitalislike substance found in low renin hypertension.

Anesthesia↗
PubMed1988

Effect of maternal ketorolac administration of platelet function in the newborn.

Ketorolac is a potent analgesic agent with antiplatelet properties which is known to cross the placenta. The aim of this study was to determine whether maternal administration of ketorolac in labour had any effect on neonatal platelet function as compared with maternal administration of pethidine and prochlorperazine. Eighteen parous women were studied in labour, twelve received pethidine (control) and six received ketorolac for analgesia. Immediately after delivery, blood was taken from the umbilical vein and anticoagulated with citrate. Platelet aggregation in whole blood was studied. Ketorolac significantly inhibited aggregation in response to arachidonic acid and collagen but not ADP. These findings confirm that ketorolac crosses the placenta. The antiplatelet effects are likely to be related to ketorolac's inhibitory effect on TxA2 production which is required for arachidonic acid and collagen-induced aggregation, but not the primary aggregation response induced by ADP. These effects suggest that ketorolac should be used with caution in patients whose neonates are at risk of haemostatic problems.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Shiley INFUSAID Pump technology.

Totally implantable drug delivery devices have been shown to be safe and effective in the delivery of drugs both systemically and regionally. Applications have been developed for continuous infusions of drugs and are currently being developed for variable flow rates with more sophisticated programmable pumps. Some of the potential benefits of such devices include improved drug efficacy with reduced systemic toxicities, more controlled dosing of drugs, improved quality of life, delivery of proteins and peptides, and individualized patient dosing. The potential exists for creating biofeedback closed loop therapies for diabetes, cardiovascular diseases, and some central nervous system diseases in the future.

Catheterization↗
PubMed1988

The effect of fasting on rat portal venous and aortic blood glucose, lactate, alanine, and glutamine.

Using a chronically catheterized rat model, the effect of fasting on portal venous, aortic, and venous blood concentration minus aortic blood concentration ([PV-A]) blood glucose, lactate, alanine, and glutamine concentrations was determined. It has been postulated that the intestine is a source of lactate and alanine, precursors for glycogen synthesis, in the fed state. After 48 h of fasting portal venous glucose, lactate, and alanine blood concentrations decreased by 31, 28, and 41%, respectively. Portal venous glutamine concentration was not affected by fasting. A glucose [PV-A] was not found in either fed or fasted states. Whereas the lactate [PV-A] was not present in fed rats, it was negative in fasted rats. Alanine [PV-A] was positive in fed and fasted rats. The glutamine [PV-A] was negative in fed and fasted rats. These data indicate that portal venous concentrations of the gluconeogenic precursors, lactate and alanine, decrease in fasted rats. In fasted rats intestinal utilization of lactate increases as reflected by a negative [PV-A]. Fasting did not affect alanine production by the intestine or glutamine utilization. Despite these changes with fasting, we conclude that the intestine does not appear to be able to maintain portal venous blood concentrations of gluconeogenic precursors.

Alanine↗
PubMed1988

Chest radiography in infant cardiac allotransplantation.

Heart transplants were performed in seven infants at Loma Linda University Medical Center from 1985 to 1987. Five of these seven patients survived. In this report, the radiographic appearance of the chest is presented before surgery, immediately after surgery, and during a documented episode of rejection. The most current available chest radiograph is also presented. Acute rejection was confirmed by clinical, echocardiographic, and ECG findings. The only pulmonary infection encountered was mycoplasma pneumonitis. Four patients developed gastrointestinal rotavirus infections and were shown to have dilated proximal small-bowel folds on upper gastrointestinal studies. At the time of this writing, the prognosis for the five surviving infants is good. We conclude that the radiographs of infants who have received heart transplants show an unusual cardiac contour and slight cardiomegaly. Increasing cardiomegaly can alert one to early rejection. Prominent folds in the small bowel are of uncertain origin and significance, but they may be related to infection resulting from immunosuppression.

Female↗
PubMed1988

A comparison of the long-term effects of sotalol and atenolol on QT interval and arrhythmias after myocardial infarction.

In order to dissociate the Class III effects of sotalol on QT interval and arrhythmias from those of chronic beta-receptor blockade, we compared the effects of sotalol 160 mg b.d. and atenolol 50 mg b.d. in a double-blind crossover study of 103 patients followed for one year after discharge following acute myocardial infarction. Sotalol caused a highly significant lengthening of the absolute and corrected QT (QTc) interval over atenolol which was apparent by day 6 and persisted unchanged throughout the follow-up period. The increase in QT interval averaged 43 ms (9%). Sotalol blunted the increase in ventricular premature beat frequency on ambulatory monitoring which occurred with atenolol, although direct comparison of arrhythmia frequency between the groups receiving atenolol and sotalol revealed no significant difference. Marked lengthening of QTc interval (greater than 500 ms) was observed on 29 occasions in patients receiving sotalol, most commonly at day 6, but no episodes of polymorphic ventricular tachycardia were recorded. The Class III action of sotalol persists over and above any response to beta-blockade during a one-year follow-up period. In a population with a low incidence of spontaneous arrhythmias, however, there was only a modest difference in antiarrhythmic efficacy between atenolol and sotalol. Episodes of marked lengthening of QT interval induced by sotalol in the absence of other adverse factors need not be arrhythmogenic.

Adult↗
PubMed1988

Borborygmia I.

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Humans↗