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Biomedical subjects

D J Phillips

Publications and source records attributed to D J Phillips.

At least 91 records · Page 5Linked to original sources

Effects of modifying gonadotrophin-releasing hormone input before and after the oestrogen-induced LH surge in ovariectomized ewes with hypothalamo-pituitary disconnection.

The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 micrograms oestradiol benzoate (OB). The ewes were given a bolus pulse of 2.25 micrograms GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P less than 0.05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P less than 0.05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. In experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 micrograms/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P less than 0.05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen.

Animals↗

Testing ultrasonic pulsed Doppler instruments with a physiologic string phantom.

The spatial, temporal, and frequency resolution of conventional ultrasonic Doppler instruments and the time/space distortions in two-dimensional color Doppler imaging systems can be measured using a pulsatile moving string target. The diameter of the string is small compared with the Doppler sample volume, the velocity (speed and direction), acceleration and timing of the string motions are precisely known with reference to the R wave timing mark, and the spatial location of the string is known. A loop of surgical thread or monofilament fishline running between pulleys is driven by a motor that provides constant string speeds from 0.05 to 150 cm/s and variable string speeds programmed to mimic arterial velocity waveforms from the carotid, aortic, and femoral arteries. Constant string speeds are used to evaluate the Doppler sensitivity, frequency processing, and sample volume size; pulsatile movement of the string provides a physiologic model to evaluate the temporal performance of conventional Doppler systems and the temporal and spatial performance of two-dimensional color Doppler imaging scanners.

Blood Flow Velocity↗

Recent advances in carotid artery evaluation.

This chapter was intended to provide an overview of ultrasound duplex scanning at the human carotid bifurcation. Although results of clinical studies are useful in patient management, much remains to be learned in the area of understanding the disease process and determining what features, obtainable by ultrasound, will predict clinical outcome. Listed below are the important points covered by this chapter. 1. Ultrasound duplex scanning can detect and quantify carotid artery disease with respect to the gold standard of contrast arteriography. 2. Contrast arteriography is not the ideal gold standard for assessment of cartotid artery disease. A new standard incorporating attributes of not only anatomy but also physiology is needed. 3. Using currently available ultrasound systems it is not possible to obtain the Doppler angle (i.e., the angle formed by the transducer axis and the blood flow-velocity vector). This angle is often estimated by the angle formed by the transducer axis and the axis of the blood vessel. This assumes that the flow-velocity vectors are axial, which turns out to be a poor assumption at bifurcations, curves, and sites of intraluminal disease. Specifying the Doppler angle involves assumptions that should always be kept in mind. 4. All Doppler data should be collected at the same angle formed by the sound beam relative to the vessel axis. Whereas results of Doppler studies can be reported in units of either frequency or velocity, assumptions made about the Doppler angle and acquiring data at arbitrary angles can produce large errors when quantifying flow velocities. 5. Blood flow disturbances cannot automatically be equated with the presence of disease. Some disturbances are localized secondary blood flow patterns produced by changes in vascular geometry coupled with pulsatile flow. 6. The lack of blood flow disturbances cannot automatically be equated with a normal or disease-free artery. Accumulation of plaque within the sinus region at the minimal and moderate disease stages appears to eliminate or attenuate local flow disturbances characteristic of a normal bifurcation. 7. An understanding of the blood flow patterns at clinical sites of interest is important to the correct interpretation of data. Both the imaging and pulsed Doppler modalities are essential to this understanding: the imaging capability to place the pulsed Doppler sample volume and appreciate changes in vascular anatomy, and the pulsed Doppler to obtain the character of blood flow at specific sites within the blood vessels.

Carotid Arteries↗

Specificity and association constants of 33 monoclonal antibodies to human IgA epitopes.

We used an immunofluorescent sequential-saturation-of-antibody assay and an interactive computer program for Scatchard analysis to determine association constants (Ka) of 33 murine monoclonal antibodies (Mabs) specific for human IgA epitopes. Ka ranged from 0.37 to 690 x 10(7) liters per mole (an approximate 1900-fold difference). Specificity was validated with a panel of 18 highly purified IgA1 and IgA2 myeloma proteins and secretory IgA using an immunofluorometric assay. Western blots of bacterial IgA protease digests were used to locate the epitopes of IgA specific Mabs in either the Fab, Fc, or hinge region. Mabs specific for unique epitopes on secretory IgA or free secretory component (FSC) were produced and evaluated.

Animals↗

Persistency of highly toxic coplanar PCBs in aquatic ecosystems: uptake and release kinetics of coplanar PCBs in green-lipped mussels (Perna viridis Linnaeus).

The bioaccumulation potential of three highly toxic coplanar PCB isomers [3,3',4,4'-tetrachlorobiphenyl (T(4)CB); 3,3',4,4',5-pentachlorobiphenyl (P(5)CB); and 3,3',4,4',5,5'-hexachlorobiphenyl (H(6)CB)] was investigated using green-lipped mussels (Perna viridis Linnaeus) as a bioindicator, through a transplantation experiment at two locations in Hong Kong waters. By contrast to the relatively rapid uptake and release of many other PCB isomers, the non-ortho chlorine substituted coplanar PCB congeners exhibited slow uptake and clearance. The kinetic parameters of coplanar PCBs based on lipid weight-related data, and the degree of bioaccumulation based on the proportion of coplanar PCBs in total PCBs in mussels, clearly indicate that coplanar PCBs are highly bioaccumulative in lower organisms. On the assumption that mussels are unlikely to be particularly unusual with respect to their bioaccumulation of coplanar PCBs, it appears most likely that these highly toxic and persistent PCB congeners are concentrated by all aquatic organisms, and may reach higher consumers (including humans) in quantities of toxicological concern.

Journal Article↗

Polychlorinated biphenyls (PCBs) in sediments in Hong Kong: a congener-specific approach to the study of coplanar PCBs in aquatic ecosystems.

Patterns of contamination by polychlorinated biphenyls (PCBs) were investigated in fourteen samples of coastal sediments from Hong Kong. Congener-specific analyses revealed nine sediment samples from Junk Bay to contain PCBs at concentrations ranging from 31 to 2200 ng g(-1) dry weight, concentrations generally increasing with distance north in the Bay. By contrast, five sediments from the Tolo area to the north-east of Hong Kong exhibited total PCB levels of only 6.6 to 45 ng g(-) dry weight. The patterns of relative abundance of PCB congeners in the northern Junk Bay sediments suggested the existence of ongoing source(s) of PCBs in this area; biphenyls of lower chlorination were present at high concentration in these samples. Three coplanar PCBs (3', 4, 4'-tetrachlorobiphenyl; 3,3',4,4',5-pentachlorobiphenyl; and 3,3',4,4',5,5'-hexachlorobiphenyl) were found to be present in Junk Bay sediments; these are highly toxic and are cause for concern in aquatic environments. The abundance of the three coplanar PCBs in the sediments studied was similar to that in commercial PCB mixtures, suggesting that these congeners are not enriched over other PCBs by the sediments of coastal ecosystems. It is concluded that the preferential enrichment of coplanar PCBs occurs in the biosphere, rather than in sediments.

Journal Article↗

Should results of ultrasound Doppler studies be reported in units of frequency or velocity?

There is a current tendency to report the results of ultrasound Doppler studies in units of velocity instead of Doppler frequency. This is probably motivated by the intuitive feeling that blood flow studies should naturally be reported in cm/s and the notion that "velocity" is a normalizing factor for Doppler ultrasound studies. In order to determine velocity, the Doppler angle theta or angle formed by the ultrasound beam and flow velocity vector, must be known. It is not possible, using currently available systems, to obtain an accurate estimate of this angle. The physics related to the Doppler equation are reviewed in this paper along with examples to illustrate the origin and magnitude of errors that could arise when reporting in units of velocity. Guidelines are provided for thinking about and reporting results of Doppler studies in units of velocity. An understanding of the Doppler equation and its use in clinical studies are promoted in this paper to enhance the diagnostic usefulness of Doppler ultrasound studies and to reduce serious errors which could lead to faulty information dictating patient management.

Blood Flow Velocity↗

An ultrasonic measurement of superficial femoral artery wall thickness.

An ultrasonic measurement of the superficial femoral artery wall thickness was performed on 16 volunteers. The measurement included all echogenic tissue between the lumen of the superficial femoral artery and the lumen of the superficial femoral vein. The average arterial wall plus vein wall thickness in volunteers with peripheral arterial disease was 2.13 +/- 0.87 mm, significantly greater than the 1.27 +/- 0.50 mm found in those without detectable peripheral arterial disease.

Aged↗

Recommended guide to the evaluation of permanent impairment of the temporomandibular joint.

This paper provides a method to evaluate the extent of permanent injury to the temporomandibular joint. The authors, working as the Committee on Permanent Impairment for the American Academy of Head, Facial, Neck Pain and TMJ Orthopedics, have used the same values as the American Medical Association has used in their Guides to the Evaluation of Permanent Impairment for other disk-protected and functional joints. These Guides may then serve as a tool to help physicians and dentists who treat temporomandibular joint injuries to rate the degree of permanent injury. These Guides may be combined with other areas of impairment that are already described and valued in the Guides to the Evaluation of Permanent Impairment published by the AMA. These Guides provide a range and each injury should be evaluated on an individual basis. We urge you to use these Guides conservatively and in harmony with good clinical judgement.

Disability Evaluation↗

Diagnostic significance of flow separation in the carotid bulb.

Pulsatile blood flow within the normal carotid sinus involves at least two distinct components. That near the flow divider is laminar and antegrade, whereas a boundary layer separation zone in the posterolateral aspect exhibits transient blood flow reversal. It is now possible to document these flow velocity components using pulsed Doppler ultrasound methods. When atherosclerosis develops, it preferentially involves the posterolateral bulb region, obliterating the normal configuration of the sinus with consequent loss of the flow separation zone. It was therefore hypothesized that if flow separation could be detected, it should be predictive of a normal angiogram. To assess this, we evaluated 20 symptomatic patients and two with only bruits found by duplex scanning to have flow separation in either one or both carotid bulbs and who also underwent cerebral angiography. Initial diagnoses were stroke in seven, reversible ischemic neurologic deficit in one, transient ischemic attack in 12, and bruit in two. Flow separation was bilateral in 13 patients (59%). There were 15 patients with symptoms in the territory of a carotid bulb exhibiting flow separation. By angiography, of the 35 bulbs with boundary layer separation, 27 (77%) were normal, with the remainder showing lesions that reduced the diameter of the vessel by 20% or less. Final diagnoses of the 15 patients with symptoms ipsilateral to a carotid sinus exhibiting flow separation were fibromuscular disease in two, lacunar stroke in three, dissection in two, subclavian steal in one, cardiogenic embolus in three, migraine in one, hyperventilation syndrome in one, kink of the mid-internal carotid artery in one, and no diagnosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Arteries↗

The oestrogen-induced surge of LH requires a 'signal' pattern of gonadotrophin-releasing hormone input to the pituitary gland in the ewe.

Two experiments were conducted with ovariectomized and hypothalamo-pituitary disconnected (HPD) ewes to ascertain the pattern of inputs, to the pituitary gland, of gonadotrophin-releasing hormone (GnRH) necessary for the full expression of an oestrogen-induced LH surge. The standard GnRH replacement to these sheep was to give pulses of 250 ng (i.v.) every 2h; at the onset of experimentation, pulses were given hourly. In experiment 1, groups of sheep (n = 7) were given an i.m. injection of 50 micrograms oestradiol benzoate, and after 10 h the GnRH pulse frequency or pulse amplitude was doubled. Monitoring of plasma LH concentrations showed that a doubling of pulse frequency produced a marked increase in baseline values, whereas a doubling of amplitude had little effect on the LH response. In a second experiment, ovariectomized HPD sheep that had received hourly pulses of GnRH for 16 h after an i.m. injection of oil or 50 micrograms oestradiol benzoate were given either a 'bolus' (2.25 micrograms GnRH) or a 'volley' (500 ng GnRH pulses 10 min apart for 30 min, plus a 500 ng pulse 15 min later). Both groups then received GnRH pulses (250 ng) every 30 min for the next 13 h. Oestrogen enhanced the LH responses to the GnRH treatments, and the amount of LH released was similar in ovariectomized HPD ewes given oestrogen plus bolus or volley GnRH treatments and ovariectomized hypothalamo-pituitary intact ewes given oestrogen. These results suggest that the oestrogen-induced LH surge is initiated by a 'signal' pattern of GnRH secretion from the hypothalamus.

Animals↗

Estimation of association constants of 42 monoclonal antibodies to human IgG epitopes using a fluorescent sequential-saturation assay.

We measured the association constant (Ka) for 42 murine monoclonal antibodies (MAbs) to human IgG epitopes. Included are antibodies, previously evaluated in an IUIS/WHO collaborative study, to various epitopes on the four subclasses of human IgG - IgG Fc, IgG Fab, kappa, and lambda - and to selected IgG allotopes. We used a sequential-saturation immunofluorescent assay and interactive computer program to determine the Ka by Scatchard analysis. Kas ranged from unmeasurably low by this method (approximately 10(6) L/M) to 3.8 X 10(9) L/M. Some class specific MAbs had large Ka differences for different subclasses and some subclass specific MAbs had large Ka differences for molecules of the same subclass but of different light-chain types.

Antibodies, Monoclonal↗

Mussels as bioindicators of PCB pollution: a case study on uptake and release of PCB isomers and congeners in green-lipped mussels (Perna viridis) in Hong Kong waters.

The uptake and release of PCB isomers and congeners were examined in green-lipped mussels (Perna viridis) through a transplantation experiment in two locations in Hong Kong waters. Rapid rates of uptake and release of relatively less lipophilic lower-chlorinated PCBs were observed in the mussels, indicating that the primary mechanism of bioaccumulation of lipophilic pollutants in P. viridis complies with the concept of equilibrium partitioning. Thus, data for contaminant concentrations are most appropriately based upon lipid weights of samples when using mussels as bioindicators of aquatic PCB pollution. Considering the kinetic parameters of PCBs based on lipid weight-related data, it is concluded that P. viridis has the ability to respond rapidly to changes in ambient levels of PCBs. This is significant in determining the usefulness and limitations of mussels as bioindicators for monitoring programmes investigating aquatic pollution by PCBs.

Journal Article↗

Variability in measurement of specific parameters for carotid duplex examination.

The variability of four carotid artery frequency parameters used for classifying disease with duplex scanning was prospectively studied. Forty-eight patients (94 patent carotid arteries) were each examined by two technologists. Measured parameters were the peak systolic frequency (PSF) and the first zero slope from the common carotid artery, and the PSF and end diastolic frequency (EDF) from the internal carotid artery. Measurements from all the examinations were made twice by each technologist. Interobserver, intraobserver, and interpatient variability in measurement of the first zero slope was so great that we have abandoned its use. Measurement of variability for PSF and EDF was much less (correlation coefficients 0.68 to 0.92). These parameters were measured with sufficient precision to warrant their continued use for important decision steps in classifying carotid artery disease. Interpatient differences in PSF sufficient to cause disagreement regarding the hemodynamic significance of carotid disease occurred in only three instances. In each of these cases the differences were due to examination technique (failure to identify a very distal internal carotid artery stenosis, difficulty distinguishing between a kink and a stenosis, and failure to recognize an improper Doppler angle). We conclude that the variability of PSF and EDF is within clinically acceptable levels and is mainly due to examination technique rather than measurement of waveform parameters or changes in patient hemodynamics.

Arterial Occlusive Diseases↗

Noninvasive assessment of normal carotid bifurcation hemodynamics with color-flow ultrasound imaging.

The combination of a B-mode imaging system and a single range-gate pulsed Doppler flow velocity detector (duplex scanner) has become the standard noninvasive method for assessing the extracranial carotid artery. However, a significant limitation of this approach is the small area of vessel lumen that can be evaluated at any one time. This report describes a new duplex instrument that displays blood flow as colors superimposed on a real-time B-mode image. Returning echoes from a linear array of transducers are continuously processed for amplitude and phase. Changes in phase are produced by tissue motion and are used to calculate Doppler shift frequency. This results in a color assignment: red and blue indicate direction of flow with respect to the ultrasound beam, and lighter shades represent higher velocities. The carotid bifurcations of 10 normal subjects were studied. Changes in flow velocities across the arterial lumen were clearly visualized as varying shades of red or blue during the cardiac cycle. A region of flow separation was observed in all proximal internal carotids as a blue area located along the outer wall of the bulb. Thus, it is possible to detect the localized flow patterns that characterize normal carotid arteries. Other advantages of color-flow imaging include the ability to rapidly identify the carotid bifurcation branches and any associated anatomic variations.

Adult↗

Diastolic flow as a predictor of arterial stenosis.

With a pulsed Doppler imaging system, it is now possible to interrogate sites from the aorta to the popliteal trifurcation. To determine which velocity parameters could be correlated with the degree of disease as determined by angiography, 34 arterial stenoses identified by scanning were also evaluated by contrast arteriography and classified in 10% increments. The angiographic readings were blinded with respect to the scan results. Four hand-measured parameters from velocity waveforms obtained at the site of stenosis were correlated with the angiogram--peak systolic velocity, systolic rise time, diastolic reverse velocity, and diastolic reverse flow time. When diastolic reverse flow was absent, diastolic forward flow was recorded. To describe diastolic flow along a continuum, diastolic reverse velocity was ascribed a positive value and diastolic forward velocity was ascribed a negative value. A systolic velocity gradient (peak velocity/rise time) was also calculated. The relationship between the angiographic categories and the measured parameters was evaluated with the Jonkheere-Terpstra trend test. A trend was determined with diastolic flow (diastolic reverse flow or diastolic flow velocity) that was significant (p less than 0.01). The linear regression was calculated (y = 40.8 + [-5.6X]), and correlation coefficient was obtained (r = 0.76) that was statistically significant (p less than 0.01). The method enables mapping and calculation of arterial stenoses by noninvasive means. This can be expected to obviate the need for diagnostic angiograms in certain and select cases in which angioplasty can be expected to be beneficial. It also affords a convenient quantitative means of following lesions over time.

Angiography↗