Chemotherapy for small cell lung neoplasms.
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Carcinoid Tumor↗
Biomedical subjects
J Briggs
Publications and source records attributed to J Briggs.
Experimental examination of cavity ionisation theory applied to alpha-particle fields.
The form of a general theory of cavity ionisation is outlined and its applications to alpha-particle fields considered. The attenuation of the alpha particles within the cavity, which gives rise to the weighting factor in general cavity theory, is considered in detail and an appropriate treatment for alpha-particle fields developed. Apparatus, consisting of an ionisation chamber composed of electrodes emitting alpha rays, was constructed in order to impose a rigorous test on the theory in the most critical region of cavity size. The general theory of cavity ionisation as applied to alpha-particle fields is shown to be in close agreement with the experimental results. As in the case of photon and electron fields, it is possible to characterise a cavity by a single chord length (path length) but the charged particle energy spectrum and the variation of stopping power with energy must be considered in detail.
Alpha Particles↗
Fluorescence fluctuation immunoassay.
The homogeneous fluorescent immunoassay described above allows one to measure the brightness of fluorescently tagged carrier particles that are suspended in a background of free, unbound fluorescent sources. We have demonstrated the feasibility of our technique using a gentamicin competitive assay as well as idealized model systems. We have seen that the fluctuation-correlation method is able to discriminate against free background sources because each fluorescing particle in solution contributes to the correlation peak [Eq. (4)] with a weighting equal to the square of its respective intensity. Hence, a few very bright sources contribute disproportionately to the "signal" relative to many weak ones. To take advantage of this property, one would therefore design an assay that uses relatively larger carrier particles, each of which is capable of binding on the order of 10(3) to 10(4) tagged antibodies or antigens. Unfortunately, the nonlinear dependence of the correlation peak on the brightness of the fluorescing species causes the technique to be perturbed by carrier particle aggregation; the apparent bound fluorescence intensity increases with the extent of aggregation. The latter may be an unavoidable consequence of performing assays using raw blood serum, for example. The ultimate usefulness of this method will depend on its sensitivity and speed when applied to "real" assays of clinical significance. These characteristics will be influenced by a number of technical details. Given our limited experience with the method thus far, it would appear that its principal drawback is its relatively slow speed. In order to decrease the time needed for a reliable measurement, one must average the random fluctuations in the fluorescent intensity to zero more quickly. In principle, this can be accomplished by decreasing the shot noise by collecting a larger fraction of the fluorescent light, and increasing the sampling rate. The method requires rather complicated instrumentation; it is by no means clear that this level of complexity is justified given the realistic level of sensitivity that will be obtained by this technique.
Antigens↗
Psychiatric hospital versus community treatment: the results of a randomised trial.
One hundred and twenty patients presenting for admission were randomly allocated into two groups. Controls received standard hospital care and after-care. Projects were not admitted if this could be avoided; instead they and their relatives were provided with comprehensive community treatment and a 24-hour crisis service. Patients with a primary diagnosis of alcohol or drug dependence, organic brain disorder or mental retardation were excluded. During the 12 months study period, 96% of controls were admitted, 51% more than once. Of the projects, 60% were not admitted at all and only 8% were admitted more than once. Controls spent an average of 53.5 days in psychiatric hospitals; projects spent an average of 8.4 days. Community treatment did not increase the burden upon the community, was considered to be significantly more satisfactory and helpful by patients and their relatives, achieved a clinically superior outcome, and cost less than standard care and after-care.
Australia↗
Value of computed tomography of the abdomen and chest in investigation of Cushing's syndrome.
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Abdominal Neoplasms↗
Further evidence for an inverse relationship between macula densa NaCl concentration and filtration rate.
It has been concluded that tubulo-glomerular feedback mechanism is triggered by changes in NaCl concentration ([NaCl]) at the macula densa. This conclusion is based on the demonstration that changes in filtration rate produced during retrograde perfusion of the loop of Henle depend upon the perfusate [NaCl]. Experiments were performed to evaluate whether the effect on glomerular function of orthograde perfusion of the loop of Henle is consistent with this conclusion. Early proximal flow rate (VEP), stop-flow pressure (PSF), early distal chloride concentration ([C]), and flow rate were measured during perfusion of the loop of Henle with mannitol solution (300 mosm kg-1), 30mM NaCl + mannitol (300 mosm kg-1), 140 mM Na isethionate and artificial tubular fluid. When distal flow exceeded 10 nl min-1, the magnitude of the glomerular response was predictable from the [Cl]. The linear regression line, delta VEP = -0.27 [Cl] + 4.3, did not differ from that obtained previously with the retrograde technique. Retrograde perfusion with 140 mM Na isethionate was without effect on VEP. We conclude that the effect on glomerular function of perfusion of the loop of Henle in either an orthograde or a retrograde direction with these solutions depends upon the chloride concentration at the macula densa.
Animals↗
Perceived self-efficacy, outcome expectancies, and negative mood states in end-stage renal disease.
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Adaptation, Psychological↗
In situ studies of the distal convoluted tubule in the rat. I. Evidence for NaCl secretion.
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Animals↗
Indicator dilution using a fluorescent indicator.
In vitro and in vivo indicator-dilution measurements are made with a fluorescent indicator and a novel detection system using a catheter containing a single optical fiber that carries both the exciting and returning fluorescent light. These fluorescent-dilution measurements are compared with simultaneous green dye-dilution measurements. The double-indicator-dilution measurement of extravascular lung water using heat and fluorescence is compared with gravimetric measurements. Also investigated is the sensitivity of the fluorescent measurement to changes in O2 saturation and hematocrit of the blood. An example of the measurement of a right-to-left heart shunt with this new indicator is given.
Animals↗
A simple steady-state model for feedback control of glomerular filtration rate.
Repeat measurements of SNGFR during different rates of microperfusion of the loop of Henle have demonstrated that the alterations of SNGFR were greatest between perfusion rates of 10 and 20 nl/min, but that changes also occurred below 10 nl/min and above 20 nl/min. By a simple curve-fitting procedure, yielding parameter estimates for single nephrons, we determined that the half-maximum response was achieved at a perfusion rate of 16.3 nl/min and that at that flow the slope of the relationship between VLP and SNGFR was 1.84. From the curve describing the perfusion response and from measurements of the proximal transport rate, we estimated that, at the operating point of the feedback loop, VLP and SNGFR should be approximately 18 and 35 nl/min, respectively. Measurements made without interruption of the feedback pathway confirmed this prediction, suggesting that perfusion adequately mimics the free-flow state. We conclude, that under the experimental conditions studied, the operating point of the feedback mechanism is located within the flow range in which the mechanism is most sensitive, so that both increases and decreases in tubular flow from the normal values should produce changes in filtration rate.
Animals↗
Concentration-dependent sodium chloride transport as the signal in feedback control of glomerular filtration rate.
There is good evidence that the initial step leading to a feedback response is the concentration-dependent active transport of sodium chloride across the macula densa cells. This may lead to changes in sodium chloride concentration or tonicity in the small and relatively unstirred compartment of the juxtaglomerular interstitium or to changes in the concentration of transport-related compounds or metabolites. We assume that the Goormaghtigh cells act as receptor cells that transform such compositional changes into a signal propagating to the glomerular vascular elements.
Animals↗
The role of opiates and endogenous opioid peptides in the regulation of rat TSH secretion.
The administration of morphine to rats at room temperature is reported to suppress serum thyrotropin (TSH) levels by a hypothalamic mechanism. However, it is unknown whether endogenous opioid peptides (EOP) are involved in the control of TSH secretion. The present studies show that naloxone (10 mg/kg, i.p.) an opiate-receptor antagonist, prevented the decline in rat serum TSH which occurs with heat exposure. Morphine sulfate (20 mg/kg, i.p.) treatment prevented the cold-induced elevation in serum TSH and pretreatment with haloperidol (0.3 mg/kg, i.p.) eliminated morphine's influence. Medial-basal hypothalamic thyrotropin-releasing hormone (TRH) content, measured by RIA, increased in the morphine-treated rats which were exposed to 4 degrees C. A submaximal intravenous dose of TRH (300 ng/100 g) was given to determine whether morphine suppresses serum TSH through the release of hypothalamic thyrotropic inhibitors. Morphine pretreatment did not alter TSH stimulation by TRH. Morphine alone or combined with TRH did not alter basal or stimulated TSH secretion in vitro. These studies strongly suggest that, in rats, the EOP modulate TSH secretion under conditions such as acute heat exposure which was associated with a decline in serum TSH. Under specific circumstances, the suppression of serum TSH by morphine may be dopamine-dependent.
Animals↗
Homogeneous fluorescent immunoassay.
A fluorescent immunoassay based on the correlation of fluctuations in particle number measures the amount of tagged species bound to micrometer-sized beads and is insensitive to background fluorescence. Without separation steps, a competitive assay can resolve I nanogram of gentamicin per milliliter from a total sample volume of only 10 microliters.
Fluorescent Antibody Technique↗
Feedback-mediated reduction of glomerular filtration rate during infusion of hypertonic saline.
An acute rise in plasma sodium concentration from 146 +/- 2.6 to 155 +/- 1.7 was produced in rats by the intraarterial infusion of 0.6 M sodium chloride (0.25 ml/min for 4 min followed by 0.25 ml/hr). A parallel fall in whole kidney GFR (from 0.45 +/- 0.02 to 0.36 +/- 0.04 ml/min per 100 g of body wt) and SNGFR measured in the distal tubule (31.4 +/- 3.01 to 27.9 +/- 2.40 nl/min) was observed. In contrast, proximally measured SNGFR (with feedback interrupted) rose from 32.7 +/- 2.73 to 37.1 +/- 2.84 nl/min. The loop of Henle flow, determined from distal SNGFR and (TF/P) inulin in late proximal fluid collected without interrupting tubular flow, rose from 13.7 +/- 1.50 to 17.0 +/- 1.42 nl/min as a consequence of a fall in proximal reabsorptive rate from 15.8 +/- 1.87 to 11.0 +/- 1.37 nl/min. Intraarterial infusion of hypertonic sodium bicarbonate resulted in comparable increases in plasma sodium concentration and inhibition of proximal reabsorption but did not produce a fall in filtration rate. We conclude (1) acute infusion of hypertonic sodium chloride results in an inhibition of proximal reabsorption and therefore in an increased rate of loop of Henle flow, (2) this increase in flow causes a fall in GFR through the tubuloglomerular feedback mechanism, and (3) acute infusion of hypertonic sodium bicarbonate does not result in a feedback-mediated fall in GFR, presumably because increased delivery of bicarbonate-rich fluid does not activate the feedback mechanism.
Animals↗
A controlled study of psychiatric hospital versus community treatment - the effect on relatives.
One hundred and twenty patients presenting at Macquarie Hospital for admission were randomly allocated into two groups. The control group patients received standard hospital care and follow-up. The project group patients were not admitted if this could be avoided; instead they were taken back to the community by the project team who provided them and their relatives with comprehensive, assertive and prolonged follow-up treatment backed by a 24-hour crisis service. The majority (63%) of the project group had no admission during the 10 month study period. Initially, the burden on the relatives of the project group was higher, but by one month it was somewhat lower and by four months it was significantly lower than the burden on the control group relatives. Relatives of the project group patients were significantly more satisfied with the treatment than control group relatives. It is clearly feasible to treat most psychiatric patients in the community without increasing the burden on their relatives.
Adolescent↗
The macula densa sensing mechanism for tubuloglomerular feedback.
A series of studies on the signal responsible for initiating the tubuloglomerular feedback (TGF)-mediated changes in SNGFR have utilized a retrograde perfusion technique that permits close control of macula densa segment tubular fluid composition. The feedback response has been demonstrated to be an approximately linear function of luminal NaCl concentration between 15 and 60 mM, with increasing NaCl concentration resulting in lower nephron filtration rate. Feedback responses could be initiated by NaCl and NaBr solutions but not by NaI, NaNO3, NaF, NaHCO3, NaSCN, or Na acetate. All chloride salts tested, in which chloride was accompanied by a univalent cation, elicited a response. The feedback mechanism thus shows a special requirement for chloride or bromide and not for sodium. With the chloride salts the response varied in magnitude depending on the accompanying cation with the following order of decreasing response, Rb+, Na+, Cs+, NH4+, K+, choline+, and Li+, CaCl2 and MgCl2 did not elicit a feedback response. The feedback response was not influenced by large changes in luminal osmolarity by addition of urea, suggesting either that the feedback sensing site is water impermeable or that water movement does not influence the signal. When electrolyte-free solutions are perfused through the loop of Henle in an orthograde direction, sufficient electrolyte may enter the luminal fluid to transiently influence the feedback mechanism.
Animals↗
Fluorescence immunoassay based on long time correlations of number fluctuations.
We report the development of a fluorescence-based immunoassay technique relying on the physical phenomena of random number fluctuations and diffusion, which we review. By determining the autocorrelation of the fluctuations in the fluorescent intensity, this methid is able to measure the amount of labeled antigen or antibody that is bound to micrometer-sized carrier particles in solution. The principal advantage of this technique is its insensitivity to small, fast-diffusing sources. It also discriminates against weakly fluorescent contaminants of size comparable to the carrier particles. We demonstrate these attributes by using two model systems: a human IgG assay and an idealized system consisting of polystyrene fluorescent spheres and rhodamine dye.
Antigen-Antibody Complex↗
Autofeedback of prolactin in cultured prolactin-secreting pituitary cells.
Cultured GH3 rat pituitary tumor cells which secrete prolactin (PRL) were used to study autoregulation of rat PRL (rPRL) secretion. Acute (1 h) release of rPRL by cells in monolayer culture was inhibited by ovine PRL (oPRL; 10(-7) and 10(-8) M). Intracellular rPRL accumulation was not inhibited by exogenous oPRL. No effect of oPRL was seen during long-term (12-day) incubation of cells with oPRL (10(-7) to 10(-9) M). oPRL exerts an acute suppressive effect on rPRL release at the cellular level, but does not inhibit rPRL synthesis or long-term release.
Animals↗