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Biomedical subjects

J H Anderson

Publications and source records attributed to J H Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Experimental treatment of thrombotic vascular occlusion.

The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

BCNU stability as a function of ethanol concentration and temperature.

BCNU is increasingly used in low ethanol (ETOH) concentrations, 5% dextrose-water (D5W), or normal saline (NS) solutions, especially for intra-arterial and prolonged (e.g., 3 day) intravenous (IV) infusions. Little work, however, has been done to evaluate BCNU decomposition rates in concentrations, diluents, and temperatures similar to those employed clinically. This study examined BCNU solutions in ETOH, NS, and D5W to evaluate, conclusively, initial recovery and decomposition rates in these three diluents. Initial BCNU recovery rates were: 95.6 +/- 0.3% (100% D5W), 89.6 +/- 0.5% (15% ETOH), and 85.2 +/- 0.5% (NS) (P less than 0.001). Study of all solutions revealed no measurable BCNU decomposition over 24 hrs (0 degrees C) and no significant difference in decomposition rates between any of the diluents (19.5 degrees C). At 37 degrees C, the solutions showed different half-lives: 14.3 +/- 0.19 hrs (15% ETOH), 10.6 +/- 0.02 hrs (10% ETOH), 8.2 +/- 0.21 hrs (5% ETOH), 7.3 +/- 0.06 hrs (NS), and 6.8 +/- 0.07 hrs (D5W) (P less than 0.001). Decomposition rates between all three temperatures (19.5 degrees C, 37 degrees C, and 50 degrees C) were significantly different (P less than 0.01) for each diluent. Dissolving BCNU powder into either D5W or NS required only 5 min when hand-shaken at body temperature. This study of initial recovery and decomposition rates suggests that, although BCNU decomposition rates were significantly increased at body temperature (37 degrees C), it was quite low and essentially unaffected by different diluents at room temperature (i.e., 19.5 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Carmustine↗
PubMed1991

Changes in the dynamics of the vertical vestibulo-ocular reflex due to linear acceleration in the frontal plane of the cat.

The vertical and horizontal components of the vestibulo-ocular reflex (VOR) were recorded in alert, restrained cats who were placed on their sides and subjected to whole-body rotations in the horizontal plane. The head was either on the axis or 45 cm eccentric from the axis rotation. During off-axis rotation there was a change in the linear force acting on the otolith organs due to the presence of a centripetal acceleration along the animal's vertical axis. Otolith forces (defined to be opposite to the centripetal acceleration) directed ventrally with respect to the animal (negative) decreased both the amplitude and time constant of the first-order approximation to the slow phase eye velocity of the vertical vestibulo-ocular reflex (VVOR). Otolith forces directed dorsally (positive) increased the amplitude and time constant. The effects were greater for the up VOR. The asymmetry in the VVOR time constant also depended on the otolith forces, being less in the presence of negative otolith forces that caused the resultant otolith force to move ventrally, towards the direction along which gravity normally acts when the animal is in the upright position. The effects of otolith forces on the up VVOR were independent of whether the animals were tested in the dark or in the light with a stationary visual surround (i.e., during visual suppression). In contrast, the changes in the time constant of the down VVOR were smaller during visual suppression. Simulations of the eye velocity storage mechanism suggest that the gain of the feedback in the storage integrator was modified by the angle between the resultant otolith force and an animal-fixed reference. This could be the animal's vertical, i.e., the direction along which gravity normally acts. For larger angles the feedback was less and the amplitude and time constant of the VVOR increased. The transformation of the otolith input was the same for both the up and down VOR, even though the final effect on the eye velocity was asymmetric (larger for up VOR) due to a separate, asymmetric gain element in the velocity storage feedback pathway.

Acceleration↗
PubMed1991

The horizontal vestibulo-ocular reflex during linear acceleration in the frontal plane of the cat.

Horizontal and vertical eye movements were recorded in alert, restrained cats that were subjected to whole-body rotations with the horizontal semicircular canals in the plane of rotation and the body centered on the axis or 45 cm eccentric from the axis of rotation. Changes in the horizontal vestibulo-ocular reflex (HVOR) due to the resultant of the linear forces (i.e., gravity and linear acceleration) acting on the otolith organs were examined during off-axis rotation when there was a centripetal acceleration along the animal's interaural axis. The HVOR time constant was slightly shortened when the resultant otolith force was not parallel to the animal's vertical axis. This effect was independent of the direction of the otolith force relative to the direction of the slow phase eye velocity. No effect on the HVOR amplitude was observed. In addition to changes in the HVOR dynamics, a significant vertical component of eye velocity was observed during stimulation of the horizontal canals when the resultant otolith force was not parallel with the animal's vertical axis. The effect was greater for larger angles between the resultant otolith force and gravity. An upward or downward component was elicited, depending on the direction of the horizontal component of eye velocity and the direction of the resultant otolith force. The vertical component was always in the direction that would tend to align the eye velocity vector with the resultant otolith force and keep the eye movement in a plane that had been rotated by the angle between the resultant otolith force and gravity.

Acceleration↗
PubMed1991

Arteriovenous shunting in patients with colorectal liver metastases.

The outlook for patients with colorectal liver metastases is poor. Microspheres have been combined with cytotoxics and administered via the hepatic artery in an attempt to improve tumour drug exposure within the liver. However, it has been suggested that arteriovenous connections might occur in association with intrahepatic tumours causing loss of regional advantage, and that the administration of microspheres further exacerbates arteriovenous shunting. In seven patients with colorectal liver metastases, base-line shunting was measured using a tracer quantity of radio-labelled albumin microspheres. The shunted fraction of a 'therapeutic quantity' of microspheres was subsequently measured in the same group of patients using albumin microspheres carrying a different radio-label. Base-line shunt for 0.5 x 10(6) microspheres was found to be 2.2 +/- 1.8% (mean +/- s.d.); the percentage shunt of a therapeutic quantity (40-80 x 10(6)) of microspheres was 3.0 +/- 0.8%. We conclude that arteriovenous shunting in patients with colorectal liver metastases is minimal, and is not significantly increased by the administration of therapeutic quantity of microspheres during regional chemotherapy.

Antineoplastic Agents↗
PubMed1991

Regional chemotherapy for inoperable renal carcinoma: a method of targeting therapeutic microspheres to tumour.

Regionally-administered, drug-loaded microspheres have a potential role in the treatment of renal tumours. Vasoactive agents, for example, angiotensin II, may allow selective delivery of microspheres to tumour. The present study defines the regional advantage that may be obtained from angiotensin II by quantifying tumour and normal kidney blood flow using radiolabelled microsphere renal perfusion studies and per-operative laser-doppler flow measurements. Angiotensin II increased microsphere distribution to tumour, relative to normal kidney, by a factor of four. This enhancement was associated with an absolute increase in tumour blood flow.

Angiotensin II↗
PubMed1991

Regional delivery of microspheres to liver metastases: the effects of particle size and concentration on intrahepatic distribution.

There is increasing interest in the use of microspheres, loaded with chemotherapeutic agents, for regional therapy to hepatic metastases. It is necessary to deliver these particles predominately to tumour rather than to normal liver. This study investigates factors influencing the distribution of regionally injected microspheres. Discreet tumour was induced in rats by subcapsular hepatic inoculations of HSN cells. At 20 days, 12.5 microns, 25 microns or 40 microns diameter, radiolabelled albumin microspheres were administered, in various concentrations, via the gastroduodenal artery. Tumour to normal liver microsphere distribution ratios were determined and median values ranged from 0.1 (0.2 mg ml-1 12.5 microns microspheres) to 1.8 (20 mg ml 40 microns microspheres). Concentrated suspensions (20 mg ml-1) of large microspheres (40 microns) produced the most favourable tumour to normal liver distribution ratios. These results not only have implications for the therapeutic administration of microspheres but also for their use in blood-flow studies.

Albumins↗
PubMed1991

Localization of metastatic adrenal cortical carcinoma with Ga-67.

Data are limited on the localization of Ga-67 in primary or metastatic adrenal cortical carcinoma. We report the localization of Ga-67 to pathologically confirmed adrenal cortical carcinoma metastatic to the lung. A review of the literature revealed four patients have previously been reported to have metastatic adrenal cortical carcinoma detected on Ga-67 scan. Gallium imaging may be useful in the evaluation of patients with adrenal cortical carcinoma. SPECT imaging should further improve lesion resolution and localization.

Adrenal Cortex Neoplasms↗
PubMed1991

The biodegradation of albumin microspheres used for regional chemotherapy in patients with colorectal liver metastases.

The poor results of systemic chemotherapy for colorectal liver metastases have focussed attention on the use of regional chemotherapy. Embolizing, biodegradable particles can be coadministered with anticancer drugs to slow temporarily the arterial blood flow and increase drug uptake within the tumour-bearing liver. Alternatively, such microspheres can be loaded with cytotoxic agents and act as slow-release mechanisms following embolization. In both instances, size and rate of degradation are important. The aim of this study was to evaluate the biological degradation of albumin microspheres in the liver of patients with colorectal liver metastases. Seven patients with advanced liver metastases had a 200-250 mg bolus dose of customized albumin microspheres (diameter range: 20-40 microns), labelled throughout with covalently bound 131I, injected into the hepatic artery. The abdomen was imaged immediately before injection to give an estimation of background count rate, and daily after injection for five days. Activity-time curves were constructed for the liver region. The median biological half-time of the particles within the whole liver was 2.4 days (range: 1.5-11.7 days), but was longer in tumours than in normal liver in some patients. The rate of microsphere degradation within tumours may be an important factor in the efficacy of microsphere-based regional therapy, and can be studied accurately by the technique we have employed.

Biodegradation, Environmental↗
PubMed1991

Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys.

To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1991

The surgical treatment of ingrowing toenails.

Two prospective studies of ingrowing toenail management were conducted. In the first, 163 patients (204 ingrowing nail edges) who had not had previous surgery were randomised and treated by total nail avulsion, nail edge excision, or nail edge excision with phenolisation of the germinal matrix; recurrence rates one year postoperatively were 73%, 73% and 9% respectively. In the second study, 63 ingrowing nail edges which had recurred after previous operations underwent nail edge excision and phenolisation. There was a 5% recurrence rate and 5% incidence of dystrophy of the nail one year after operation.

Adolescent↗
PubMed1991

Transplacental passage of a human relaxin administered to rhesus monkeys.

A synthetic version of the human relaxin encoded by the human gene 2 (hR1x-2) was administered to pregnant rhesus monkeys (Macaca mulatta) on gestational days 141-158. Monkeys (three per group) received doses of 100 micrograms/kg or 2000 micrograms/kg as a continuous i.v. infusion over 2 h into a radial vein. One monkey in the low-dose group received, along with the unlabelled hR1x-2, 25.5 microCi/kg of the test material internally labelled with [35S]cysteine. Immunoreactive hR1x-2, as measured by enzyme-linked immunosorbent assay, appeared in all fetuses within 30 min (the first sampling time) of beginning the infusions. Peak fetal plasma levels of hR1x-2 were only 0.8-1.5% of the maternal values. Only 8-15% of the fetal serum radioactivity was hR1x-2. Radioactivity from maternal urine pooled over the 4-h experiment did not elute at the volume corresponding to hR1x-2, but near the column volume.

Animals↗
PubMed1991

Presence of insulin autoantibodies as regular feature of nondiabetic repertoire of immunity.

With an ultrasensitive noncompetitive enzyme-linked immunosorbent assay (ELISA), we tested the hypothesis that the presence of insulin autoantibodies in nondiabetic individuals is a normal event. Plasma and peripheral blood mononuclear cells were obtained from 50 nondiabetic whites for determination of insulin autoantibodies by ELISA and radioimmunoassay (anti-insulin IgG [AI-IgG] and 125I-labeled insulin bound [%]), islet cell antibodies, anti-nuclear antibodies and rheumatoid factor, and HLA class II-type antigens (DR, DRw, and DQ). The range of 125I-insulin binding was significantly less than was seen in pretreatment sera from individuals with diabetes (from -0.4 to 0.4% vs. -0.8 to 7.7%, respectively, P = 0.001). Eighty-eight percent of these nondiabetic individuals had significant levels of AI-IgG with preferential binding to human insulin. The geometric mean of AI-IgG concentrations in individuals with significant levels was 180 pM. Binding to human insulin was seen in 88%, to pork insulin in 42%, and to beef insulin in 24% of individuals (P less than 0.001 overall; P less than 0.05 where more bound to pork than beef insulin). Binding of AI-IgG to human insulin-coated plates was substantially inhibited by preincubation with human insulin (median inhibition 57.6%) with little if any inhibition by glucagon, C-peptide, albumin, or IgG. Four individuals had highly specific human AI-IgG as shown by immunoaffinity studies. AI-IgGs were significantly higher in individuals with the HLA haplotype DR4,DRw53,DQ3 and lower in individuals with DR5,DRw52,DQ1 (P = 0.03 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Do nasogastric feeding tubes cause gastro-oesophageal reflux in healthy subjects?

The potential relationship between nasogastric intubation and acid gastro-oesophageal reflux was investigated. Ten healthy volunteers underwent 24h oesophageal pH monitoring following intubation with (i) a pH monitor alone, (ii) a pH monitor plus a Ryles nasogastric tube and (iii) a pH monitor plus a fine-bore nasogastric feeding tube. Neither of the nasogastric intubations were associated with significant reflux.

Journal Article↗
PubMed1990

Peritoneal mesothelioma.

We report two patients who presented with small bowel obstruction secondary to peritoneal mesothelioma. The difficulties in establishing this diagnosis at an early stage are illustrated. Recent advances in the management of peritoneal mesothelioma are reviewed.

Adult↗
PubMed1990

Intra-arterial chemotherapy for brain tumors.

Direct comparisons of theoretical modeling with actual drug delivery can lead to improved brain tumor therapy. In this study, normal and brain tumor-bearing rabbits received infusions of BCNU, or carmustine (1,3-bis [2-chlorethyl]-1-nitrosourea), with ethanol or hyperoxygenated perfluorocarbons as BCNU diluent. When ethanol was used as a diluent, right (infused) hemisphere:left (noninfused) hemisphere ratios of BCNU concentrations in both rabbit groups were markedly lower than had been predicted with theoretical pharmacokinetic modeling. When perfluorocarbons were used as a diluent, ratios of BCNU were significantly improved. These laboratory studies were directly translated into a two-phase protocol for human brain tumor patients. This combined research program demonstrates the successful integration of laboratory and clinical programs.

Analysis of Variance↗