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G Stuart

Publications and source records attributed to G Stuart.

At least 19 recordsLinked to original sources
PubMed1995

Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites.

The temporal and spatial profile of activity-evoked changes in membrane potential and intracellular calcium concentration in the dendrites of hippocampal CA1 pyramidal neurons was examined with simultaneous somatic and dendritic patch-pipette recording and calcium imaging experiments. Action potentials are initiated close to the soma of these neurons and backpropagate into the dendrites in an activity-dependent manner; those occurring early in a train propagate actively, whereas those occurring later fail to actively invade the distal dendrites. Consistent with this finding, dendritic calcium transients evoked by single action potentials do not significantly attenuate with distance from the soma, whereas those evoked by trains attenuate substantially. Failure of action potential propagation into the distal dendrites often occurs at branch points. Consequently, neighboring regions of the dendritic tree can experience different voltage and calcium signals during repetitive action potential firing. The influence of backpropagating action potentials on synaptic integration and plasticity will therefore depend on both the extent of dendritic branching and the pattern of neuronal activity.

Action Potentials↗
PubMed1995

Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons.

Simultaneous somatic and dendritic recordings were made from the same neocortical layer V pyramidal neuron, and current injection via the dendritic recording pipette was used to simulate the voltage change that occurs during an EPSP. At the soma, these simulated EPSPs increased nonlinearly with the amplitude of the dendritic current injection and with depolarization of the membrane potential. Bath application of the sodium channel blocker TTX decreased large (> 5 mV) EPSPs and also blocked amplification of EPSPs at depolarized membrane potentials, whereas calcium channel blockers had little effect. Local application of TTX to the soma and axon blocked EPSP amplification, whereas dendritic application had little effect. Simultaneous somatic and axonal recordings demonstrated that EPSP amplification was largest in the axon. These results show that EPSPs are amplified by voltage-activated sodium channels located close to the soma and in the axon.

Action Potentials↗
PubMed1995

Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons.

The site of action potential initiation in substantia nigra neurons was investigated by using simultaneous somatic and dendritic whole-cell recording in brain slices. In many dopamine neurons, action potentials were observed first at the dendritic recording site. Anatomical reconstruction showed that in these neurons, the axon emerged from the dendrite from which the recording had been made. Action potentials showed little attention in the dendritic tree, which in dopamine neurons was shown to be due to recruitment of dendritic sodium channels and may be related to the dendritic release of dopamine. We conclude that in substantia nigra neurons, the site of action potential initiation, and thus the final site of synaptic integration, is in the axon. As the axon can originate from a dendrite, up to 240 microns away from the soma, synaptic input to the axon-bearing dendrite may be privileged with respect to its ability to influence action potential initiation.

Action Potentials↗
PubMed1995

Probing dendritic function with patch pipettes.

Most neurons in the CNS have complex, branching dendritic trees, which receive the majority of all synaptic input. As it is difficult to make electrical recordings from dendrites because of their small size, most of what is known about their electrical properties has been inferred from recordings made at the soma. By taking advantage of the higher resolution offered by improved optics, it is now possible to make patch-pipette recordings from the dendrites of neurons in brain slices under visual control. This new technique promises to provide valuable new information concerning dendritic function.

Animals↗
PubMed1995

Functional equivalence of verbal and spatial information in serial short-term memory.

Performance on a test of serial memory for the spatial position of a sequence of dots showed similarities to typical results from the serial recall of verbal material: a marked increase in error with increasing list length, a modest rise in error as retention interval increased, and bow-shaped serial position curves. This task was susceptible to interference from both a spatial task (rote tapping) and a verbal task (mouthed articulatory suppression) and also from the presence of irrelevant speech. Effects were comparable to those found with a serial verbal task that was generally similar in demand characteristics to the spatial task. As a generalization, disruption of the serial recall of visuospatial material was more marked if the interference conditions involved a changing sequence of actions or materials, but not if a single event (tap, mouthed utterance, or sound) was repeated.

Humans↗
PubMed1994

Initiation and spread of sodium action potentials in cerebellar Purkinje cells.

Simultaneous whole-cell recordings were made from the soma and dendrites of cerebellar Purkinje cells in rat brain slices. Sodium action potentials, evoked by either depolarizing current pulses or synaptic stimulation of parallel or climbing fibers, always occurred first at the soma and decreased in amplitude with increasing distance into the dendrites. Simultaneous somatic and axonal recordings showed that these action potentials were initiated in the axon. Outside-out patches excised from the soma and dendrites revealed that the sodium channel current density decreased with distance from the soma. Consistent with this finding, comparable attenuation was observed for evoked action potentials and simulated action potential waveforms when sodium channels were blocked. These results show that sodium action potentials in cerebellar Purkinje cells are initiated in the axon and then spread passively into the dendritic tree.

Action Potentials↗
PubMed1994

Answering a need: geropsychiatric nursing course development.

1. A part of the commitment to holistic nursing care is meeting the mental health needs of its clients. 2. There exists a great need to deal with both mental and physical problems in older persons. Moreover, geropsychiatry is greatly lacking in the policy and practice of nursing education. 3. Graduate-level courses must focus on both mental health promotion and disease prevention, particularly for the older persons who are consumers.

Aged↗
PubMed1994

Integrated ambulatory care resource scheduling in oncology.

In a modern managed-care environment, the scheduling of ambulatory care activities must be viewed as a series of closely related activities rather than a group of unique and independent events. These activities must be sequenced in a logical manner, and linked with a variety of information on other clinical, operational, and administrative activities. This article focuses on such an integrated scheduling system which supports the ambulatory care services at the Johns Hopkins Oncology Center.

Ambulatory Care Information Systems↗
PubMed1993

Intraventricular morphine for intractable pain of advanced cancer.

Among the most difficult pain management problems are those associated with advanced head and neck cancer, and those in which pain is midline, bilateral, or diffuse. The authors report effective control of intractable pain in 52 patients by injection of small doses of morphine via an Ommaya or a Cordis reservoir into the lateral cerebral ventricle. The technique is safe and effective. The reservoir is usually inserted under local analgesia so the method of pain relief is available to patients in whom general anesthesia would be difficult or contraindicated. The doses of morphine required to maintain analgesia remain remarkably low. Tolerance reported by other authors has not been a problem when preoperative assessment of the patient has been thorough. Maximum survival time has been 75 wk and another patient has lived 65 wk. Complications included two colonized reservoirs, one dislodged ventricular catheter, three blocked catheters, and one postoperative meningitis. For patients with diffuse midline or bilateral pain, or intractable pain associated with advanced head and neck cancer, the use of intraventricular morphine should be considered when satisfactory pain relief is not achieved with oral morphine or continuous subcutaneous infusion.

Aged↗
PubMed1992

Endocarditis with acute mitral regurgitation caused by Fusobacterium necrophorum.

Infective endocarditis is uncommon in young children, especially in the absence of structural heart disease. We report the case of a 2-year-old boy who presented with acute rupture of the mitral valve chordae 6 weeks after an episode of Fusobacterium necrophorum septicemia. His heart had been structurally normal before. Mitral valve replacement was successfully performed. This is the first recorded case of endocarditis in a child caused by necrobacillosis.

Bacteremia↗
PubMed1992

The effect of estrous cycle and buthionine sulfoximine on glutathione release from the in vitro perfused rat ovary.

There is little known regarding the intracellular mechanisms of modification of damage in the ovary. Ovarian perfusion of en block dissections of the rat right ovary with aorta and vena cava were done to determine (a) if glutathione (GSH) is released by the ovary, (b) if the release is cycle dependent, and (c) if GSH released is the product of de novo ovarian synthesis. All perfused ovaries released GSH and the release was maximal at estrus and least at metestrus. Perfusion with buthionine sulfoximine, a specific inhibitor of gamma-glutamylcysteine synthetase, resulted in a dose-dependent reduction in GSH released, indicating inhibition of de novo synthesis during perfusion.

Animals↗
PubMed1992

Regulation of total ovarian glutathione content in the rat.

Glutathione (GSH) is an important intracellular thiol capable of altering metabolism following exposure to certain important biologic toxicants including radiation and cyclophosphamide. In order to evaluate the inhibition of glutathione synthesis in the ovary, 30-day-old Sprague Dawley rats were treated with either saline or 0.6 mumol/kg (0.133 mg/kg), 6.0 mumol/kg (1.33 mg/kg), or 4.5 mmol/kg (1000 mg/kg) buthionine sulphoximine (BSO) IP and sacrificed at 0, 1, 2, 4, 6, 8, and 24 h. There was an inhibition of glutathione synthesis with 4.5 mmol/kg (1000 mg/kg) BSO with a nadir at 8 h (P less than 0.001) and complete recovery at 24 h. In the subsequent experiments rats were divided into four groups. All animals received either saline or BSO 4.5 mmol/kg/day (1000 mg/kg/day) from day 27 to 30 of life and either saline or PMSG 5 IU IP on day 29 of life. BSO reduced ovarian content of GSH (saline-saline compared with BSO-saline, P less than 0.0001), which was countered by the prior administration of PMSG (BSO-saline compared with BSO-PMSG, P less than 0.005). Glutathione levels were as follows: saline-saline 4.3 +/- 0.04; saline-PMSG 5.0 +/- 0.4; BSO-saline 2.13 +/- 0.2; BSO-PMSG 3.24 +/- 0.2 nmol/mg ovary. These findings suggest the ovary is susceptible to GSH depletion by in vivo administration of BSO. Gonadotropin (PMSG) is capable of effecting a partial return of total ovarian GSH content.

Animals↗
PubMed1992

Research resources.

Explore the source record for details and available documents.

Community Mental Health Services↗
PubMed1992

Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.

In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Adult↗
PubMed1990

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study.

The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

Administration, Cutaneous↗
PubMed1990

Relationship of psychotic symptoms to haloperidol-stimulated prolactin release.

Prolactin (PRL) response to a single dose of intravenous haloperidol (0.5 mg) was measured as a marker of tuberoinfundibular dopamine (TIDA) activity in 24 neuroleptic-free, male, psychotic patients. The PRL responses were then correlated with psychotic symptoms measured with Andreasen's Scales for the Assessment of Positive and Negative Symptoms (SAPS, SANS). Correlation analyses revealed a significant inverse relationship between PRL response and the severity of delusional symptoms. There was no significant correlation between the symptoms of hallucinations, formal thought disorder, or global negative symptoms and PRL response to haloperidol, nor were there any significant correlations between basal PRL and symptom severity. These results suggest that among the positive and negative symptoms associated with psychoses, only delusions may be associated with TIDA overactivity.

Adult↗