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D Johnston

Publications and source records attributed to D Johnston.

At least 91 records · Page 5Linked to original sources
PubMed1998

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TG de principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively, p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Activities of Daily Living↗
PubMed1998

Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons.

This review discusses recent data regarding the different types of voltage-gated Na+, Ca2+, and K+ channels in dendrites of CA1 pyramidal neurons and their function for synaptic integration and plasticity. Na+ and Ca2+ channels are uniformly distributed throughout the dendrites, although Na+ channels in the soma and proximal dendrites differ in their inactivation properties from Na+ channels in more distal regions. Also, different regions of the neuron express different subtypes of Ca2+ channels. K+ channels are unevenly distributed, with the distal dendrites expressing a more than fivefold greater density of a transient A-type K+ channel than proximal regions. These K+ channels exert profound control over the excitability of the pyramidal neurons and the spread of synaptic potentials throughout the dendrites. The ways in which the active properties of dendrites may contribute toward the induction and maintenance of long-term synaptic plasticity are discussed.

Animals↗
PubMed1998

Implications of the results of community intervention trials.

This paper examines the results of population-level interventions conducted in three settings: entire communities, worksites, and schools. Four major conclusions are discussed: (a) Directions for the next generation of community-based interventions include targeting multiple levels of influence; addressing social inequalities in disease risk; involving communities in program planning and implementation; incorporating approaches for "tailoring" interventions; and utilizing rigorous process evaluation. (b) In addition to randomized controlled trials, it is time to use the full range of research phases available, from hypothesis generation and methods development to dissemination research. (c) The public health research agenda may have contributed to observed secular trends by placing behavioral risk factors on the social and media agendas. (d) The magnitude of the results of community intervention trials must be judged according to their potential public health or population-level effects. Small changes at the individual level may result in large benefits at the population level.

Community Health Planning↗
PubMed1998

Protein kinase C activation decreases activity-dependent attenuation of dendritic Na+ current in hippocampal CA1 pyramidal neurons.

Action potentials recorded from the soma of CA1 pyramidal neurons remain relatively uniform in amplitude during repetitive firing. In contrast, the amplitudes of back-propagating action potentials in dendrites decrease progressively during a spike train. This activity-dependent decrease in amplitude is dependent on the frequency of firing during the train and distance from the soma. Previously, we described a property of Na+ channels that provides a plausible mechanism for the activity dependence of the amplitude of the dendritic action potentials: available Na+ current decreases during trains of action potentials through an inactivation, distinct from fast inactivation, that appears rapid in onset, but slow and voltage-dependent in its recovery. In this study we found that activation of protein kinase C by phorbol esters decreased this activity-dependent inactivation of pharmacologically isolated Na+ current in cell-attached dendritic, but not somatic, patches. Similarly in whole cell recordings phorbol esters decreased the attenuation of back-propagating dendritic action potentials during trains. These results indicate a novel effect of protein kinase C on the dendritic Na+ channel and further support the hypothesis that the activity dependence of the dendritic action potentials is derived from the inactivation properties of Na+ channels.

Action Potentials↗
PubMed1998

L-Type calcium channels are required for one form of hippocampal mossy fiber LTP.

The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 +/- 5% (mean +/- SE) increase in control versus 7 +/- 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 +/- 10% in control vs. 80 +/- 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl--aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

Animals↗
PubMed1998

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Antiemetics↗
PubMed1998

Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.

PURPOSE: In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS: Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS: The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). CONCLUSION: The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.

Antineoplastic Agents↗
PubMed1998

Cleft lip with or without cleft palate: effect of family history on reproductive planning, surgical timing, and parental stress.

OBJECTIVE: This study tested whether the presence of a family history of nonsyndromic cleft lip with or without cleft palate (NSCLP) lessens the negative impact on reproductive planning, decreases treatment anxiety, and relieves parental stress when there is a recurrent cleft. DESIGN: Sixty-one participating families, retrospectively ascertained through their children with NSCLP, were divided into two groups: those with a family history of clefting and those in which only the proband was affected. SETTING: Each family completed a questionnaire either at their home or during a clinic visit. PARTICIPANTS: Questionnaires were distributed to 117 families with an NSCLP child. Of these 117, 49 (42%) had another family member with NSCLP and 68 (58%) had no prior history of clefting. Sixty-one (52%) families returned the questionnaire and were categorized by family history. MAIN OUTCOME MEASURES: The Parenting Stress Index and the Hollingshead Index of Social Position were included with family and medical history questions in the 137-item questionnaire. RESULTS: The reproductive plans of the two groups were quite similar and were not dependent on the families' actual or perceived recurrence risks of NSCLP. The majority (85%) of the children with NSCLP underwent surgical closure at the recommended age. The two groups did not significantly differ on any score on the Parenting Stress Index, indicating a similar parental stress level between the groups. CONCLUSIONS: These findings suggest that family history does not significantly influence reproductive plans, timing of cleft repair, or stress of parents of a child with NSCLP. Further, these results indicate a need for additional psychosocial study of this population.

Adolescent↗
PubMed1997

Clinical significance of negative and equivocal urinary bladder cytology alone and in combination with DNA image analysis and cystoscopy.

BACKGROUND: We evaluated the individual and combined ability of cytology (CYT), image analysis (IA), and cystoscopy (CYSTO) to predict the presence of transitional cell carcinoma (TCC) at 6 months of follow-up in patients with or without a prior history of urothelial carcinoma and negative (NEG) or equivocal (atypical or suspicious) urinary CYT. METHODS: Fifty-one patients (43 with prior TCC) provided 57 urinary samples that were evaluated by CYT and DNA IA. Forty-nine patients were evaluated by CYSTO. Disease status was reassessed at 6 months by a combination of clinical, CYSTO, CYT, and histologic follow-up. RESULTS: At 6 months' follow-up, the incidence of recurrence for patients with diploid, broad diploid, or aneuploid DNA histograms was 38%, 73%, and 100%, respectively. In the same group of patients, 43% of patients with NEG and "atypical" CYT recurred compared with 83.3% of patients with "suspicious" CYT. The predictive value (PV) of a positive (+) CYSTO evaluation was 100%; however, a NEG CYSTO examination was correct in only 73% of cases. Sensitivities of CYT, IA, and CYSTO to predict recurrence were 54%, 59%, and 62.5%, respectively, whereas the combined sensitivity of all three modalities was 72%. The +PV of combined CYT and IA in patients with prior TCC was 90% with aneuploidy 100% specific for malignancy; the NEG PV of combined CYT, IA, and CYSTO was 70%. CYT, IA, and CYSTO were highly significant in predicting recurrence (P = 0.0017, P = 0.0026, and P = 0.0002, respectively) whereas tumor grade and degree of invasiveness as assessed on initial biopsy were not significant. However, 11% of patients recurred between 6 months to 1 year who had NEG CYT, NEG CYSTO, and NEG IA. CONCLUSIONS: Diagnostic accuracy increases in patients with NEG or equivocal CYT if supplemented by DNA IA and CYSTO. In patients with no history of TCC, equivocal urine CYT and/or abnormal DNA IA can occur after chemotherapy, radiation therapy, or viral infection. In these patients, the combined approach together with accurate history is essential for correct diagnosis. For the small subpopulation of patients who recur but demonstrate no abnormalities on combined testing, more sensitive diagnostic tests, such as chromosomal abnormalities by in situ hybridization, need to be developed.

Adult↗
PubMed1997

Comparison of results of various methods used to determine the extent of modification of methoxy polyethylene glycol 5000-modified bovine cupri-zinc superoxide dismutase.

The protein bovine cupri-zinc superoxide dismutase (SOD) was modified by the reaction of lysine residues with an active ester of methoxy polyethylene glycol 5000 (PEG). The extent of modification was determined by capillary zone electrophoresis, matrix-assisted laser desorption/ionization mass spectrometry, Fourier-transform infrared spectroscopy, and Raman spectroscopy and after removing PEG by alkaline hydrolysis of the linkages to SOD followed by quantification of the released PEG using gel-permeation chromatography. There was generally good agreement among the results obtained by these techniques on a typical sample of the PEG-modified protein. The results, extent of protein modification, determined by the preceding methods were compared to that found from the classical trinitrobenzene sulfonic acid (TNBS) procedure. In addition to providing alternatives to the TNBS procedure, results from the described methodologies strongly suggest that the extent of modification determined from the TNBS procedure is overestimated.

Animals↗
PubMed1997

Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.

Na+ action potentials propagate into the dendrites of pyramidal neurons driving an influx of Ca2+ that seems to be important for associative synaptic plasticity. During repetitive (10-50 Hz) firing, dendritic action potentials display a marked and prolonged voltage-dependent decrease in amplitude. Such a decrease is not apparent in somatic action potentials. We investigated the mechanisms of the different activity dependence of somatic and dendritic action potentials in CA1 pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp methods. There were three main findings. First, dendritic Na+ currents decreased in amplitude when repeatedly activated by brief (2 msec) depolarizations. Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less in somatic than in dendritic patches. Third, although K+ currents remained constant during trains, K+ currents were necessary for dendritic action potential amplitude to decrease in whole-cell experiments. These results suggest that regional differences in Na+ and K+ channels determine the differences in the activity dependence of somatic and dendritic action potential amplitudes.

Action Potentials↗
PubMed1997

K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.

Pyramidal neurons receive tens of thousands of synaptic inputs on their dendrites. The dendrites dynamically alter the strengths of these synapses and coordinate them to produce an output in ways that are not well understood. Surprisingly, there turns out to be a very high density of transient A-type potassium ion channels in dendrites of hippocampal CA1 pyramidal neurons. These channels prevent initiation of an action potential in the dendrites, limit the back-propagation of action potentials into the dendrites, and reduce excitatory synaptic events. The channels act to prevent large, rapid dendritic depolarizations, thereby regulating orthograde and retrograde propagation of dendritic potentials.

Action Potentials↗
PubMed1997

Superimposed histologic and genetic mapping of chromosome 17 alterations in human urinary bladder neoplasia.

Multistep alterations of chromosome 17 in the progression of human urinary bladder neoplasia were studied by superimposed histologic and genetic mapping. The p53 gene was included in the analysis as a model tumor suppressor gene that is frequently involved in urothelial carcinogenesis. The strategy provided a systematic approach to the study of multistep genomic alterations that occur as neoplasia progresses from precursor intraurothelial conditions to invasive cancer. This was accomplished by sampling the entire mucosa of the organ and displaying microscopically identified invasive cancer and precursor conditions in the form of a histologic map. Subsequent isolation of DNA provided a set of samples in which the search for genetic alterations was performed and superimposed on the histologic map. This approach disclosed multifocal allelic losses of chromosome 17 in the early preinvasive phases of urothelial neoplasia. The alterations were predominantly confined to the p12-13, q22-11 and q24-25 regions. Mutations and allelic losses of the p53 gene were mapped to early preinvasive phases of urothelial neoplasia. The data provide detailed analysis of chromosome 17 allelic losses that occur in the development and progression of urothelial neoplasia and represent the first step for genome-wide modeling of multistep human urothelial carcinogenesis.

Alleles↗
PubMed1997

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma.

BACKGROUND: Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome. METHODS: DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS: There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Adenocarcinoma↗
PubMed1997

Delays in the diagnosis of oesophagogastric cancer: a consecutive case series.

OBJECTIVES: To examine the time taken to diagnose oesophageal or gastric cancer, identify the source of delay, and assess its clinical importance. DESIGN: Study of all new patients presenting to one surgical unit with carcinoma of the oesophagus or stomach. SETTING: University department of surgery in a large teaching hospital. SUBJECTS: 115 consecutive patients (70 men, mean age 66 years) with carcinoma of the oesophagus (27) or stomach (88). MAIN OUTCOME MEASURES: Interval from the onset of symptoms to histological diagnosis, final pathological stage of the tumour, and whether potentially curative resection was possible. RESULTS: The median delay from first symptoms to histological diagnosis was 17 weeks (range 1 to 168 weeks). 25% (29/115) of patients had a delay of over 28 weeks (median 39 weeks). Total delay was made up of the following components: delay in consulting a doctor (29%), delay in referral (23%), delay in being seen at hospital (16%), and delay in establishing the diagnosis at the hospital (32%). No relation was found between delay in diagnosis and tumour stage in patients with gastric cancer, but for oesophageal cancer those with stage I and II disease were diagnosed within 7 weeks compared with 21 weeks (P < 0.02) for those with stage III and IV disease. CONCLUSIONS: Long delays still occur in the diagnosis of patients with cancer of the stomach or oesophagus. Streamlined referral and investigation pathways are needed if patients with gastric and oesophageal carcinomas are to be diagnosed early in the course of the disease.

Aged↗
PubMed1997

A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons.

The role of back-propagating dendritic action potentials in the induction of long-term potentiation (LTP) was investigated in CA1 neurons by means of dendritic patch recordings and simultaneous calcium imaging. Pairing of subthreshold excitatory postsynaptic potentials (EPSPs) with back-propagating action potentials resulted in an amplification of dendritic action potentials and evoked calcium influx near the site of synaptic input. This pairing also induced a robust LTP, which was reduced when EPSPs were paired with non-back-propagating action potentials or when stimuli were unpaired. Action potentials thus provide a synaptically controlled, associative signal to the dendrites for Hebbian modifications of synaptic strength.

Action Potentials↗
PubMed1997

One-stage restorative proctocolectomy without temporary ileostomy for ulcerative colitis: a note of caution.

PURPOSE: This study was designed to determine the safety of omitting a temporary defunctioning ileostomy in restorative proctocolectomy for ulcerative colitis. METHOD: One hundred consecutive patients with ulcerative colitis were treated electively by restorative proctocolectomy and pouch-anal anastomosis, without mucosal stripping; 50 had a defunctioning ileostomy added, and 50 underwent a one-stage procedure without ileostomy. RESULTS: There was no operative mortality. The incidence of postoperative complications was similar in the two groups of patients. Life-threatening complications, however, were more common among patients who did not have a defunctioning ileostomy, of whom 11 developed pelvic sepsis and 7 required reoperation. Among patients with an ileostomy, seven developed pelvic sepsis but none required reoperation (P < 0.02). Emergency reoperations were required in 11 patients without an ileostomy but in only 1 patient with an ileostomy (P < 0.01). CONCLUSION: One-stage restorative proctocolectomy without a defunctioning ileostomy is associated with increased risk to life. Its routine use cannot be recommended.

Adolescent↗